RINVOQ® (upadacitinib) - Healthcare Professional Site (2024)

Table of Contents

CONTROL THAT'S FAST AND SHOWN TO LAST Rapid Remission1,4 Durable Control5,6 Well-Studied Safety1,12 Exceptional Access and Patient Support2 See how UPADAC Complete provides an exceptional accessand patient support experience IMPORTANT SAFETY INFORMATION & INDICATIONS1 INDICATIONS1 IMPORTANT SAFETY INFORMATION FOR RINVOQ/RINVOQ LQ (upadacitinib) SERIOUS INFECTIONS MORTALITY MALIGNANCIES MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE) THROMBOSIS HYPERSENSITIVITY GASTROINTESTINAL PERFORATIONS LABORATORY ABNORMALITIES EMBRYO-FETAL TOXICITY VACCINATION MEDICATION RESIDUE IN STOOL LACTATION HEPATIC IMPAIRMENT ADVERSE REACTIONS SELECT-CHOICE Primary Endpoint1 DATA LIMITATIONS Baseline Characteristics1 REFERENCES SELECT-COMPARE PRIMARY ENDPOINT1 SELECT RANKED SECONDARY ENDPOINTS2 SELECT PRESPECIFIED NONRANKED ENDPOINTS3,9,10 DATA LIMITATIONS BASELINE CHARACTERISTICS3,11 REFERENCES SELECT-MONOTHERAPY Primary Endpoint1 Select Ranked Secondary Endpoints3,6 SELECT PRESPECIFIED NONRANKED ENDPOINTS3,6 Data Limitations Baseline Characteristics3 REFERENCES SELECT‑EARLY Primary Endpoint1 Ranked Secondary Endpoints3,8 Select prespecifiednonranked endpoints2,3,9,10 Data Limitations Baseline Characteristics3 REFERENCES SELECT-NEXT Primary Endpoint1 Select Ranked Secondary Endpoints5,6 Select Prespecified nonranked endpoints6 Data Limitations Baseline Characteristics5 REFERENCES SELECT-BEYOND Primary Endpoint1 Ranked Secondary Endpoints6,7 Select Prespecified nonranked endpoints7 Data Limitations Baseline Characteristics6 REFERENCES SELECT-BEYOND Primary Endpoint1 Ranked Secondary Endpoints6,7 Select Prespecified nonranked endpoints7 Data Limitations Baseline Characteristics6 REFERENCES SELECT‑EARLY Primary Endpoint1 Ranked Secondary Endpoints3,8 Select prespecifiednonranked endpoints2,3,9,10 Data Limitations Baseline Characteristics3 REFERENCES SELECT-MONOTHERAPY Primary Endpoint1 Select Ranked Secondary Endpoints3,6 SELECT PRESPECIFIED NONRANKED ENDPOINTS3,6 Data Limitations Baseline Characteristics3 REFERENCES SELECT-NEXT Primary Endpoint1 Select Ranked Secondary Endpoints5,6 Select Prespecified nonranked endpoints6 Data Limitations Baseline Characteristics5 REFERENCES SELECT-COMPARE PRIMARY ENDPOINT1 SELECT RANKED SECONDARY ENDPOINTS2 SELECT PRESPECIFIED NONRANKED ENDPOINTS3,9,10 DATA LIMITATIONS BASELINE CHARACTERISTICS3,11 REFERENCES You are about to enter a site that is for U.S. Healthcare Professionals Only. You are about to enter a site that is for US Healthcare Professionals Only. Exit Site You are about to enter a site that is for US Healthcare Professionals Only. You are about to enter a site that is for US Healthcare Professionals Only. IMPORTANT SAFETY INFORMATION & INDICATIONS1 INDICATIONS1 IMPORTANT SAFETY INFORMATION FOR RINVOQ/RINVOQ LQ (upadacitinib) SERIOUS INFECTIONS MORTALITY MALIGNANCIES MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE) THROMBOSIS HYPERSENSITIVITY GASTROINTESTINAL PERFORATIONS LABORATORY ABNORMALITIES EMBRYO-FETAL TOXICITY VACCINATION MEDICATION RESIDUE IN STOOL LACTATION HEPATIC IMPAIRMENT ADVERSE REACTIONS FAQs

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Rheumatoid Arthritis
- Rheumatoid Arthritis
- Psoriatic Arthritis
- Ankylosing Spondylitis
- Non-radiographic Axial Spondyloarthritis
- Polyarticular Juvenile Idiopathic Arthritis
- Juvenile Psoriatic Arthritis
- Atopic Dermatitis
- Ulcerative Colitis
- Crohn's Disease
Home
Clinical Remission
- Remission + LDA at Weeks 12 and 14
- Remission out to ~5 years
- LDA out to ~5 years
Safety Profile
- Data Up to 12 Months
- Long-term Exposure Data
- Monitoring and Dose Interruptions
- Important Safety Information
- Commercial Access
- RINVOQ Complete
- How to Enroll Patients
- Downloadable Resources
- Dosing
- Monitoring
- Mechanism of Action

For moderate to severe rheumatoid arthritis (RA) in adult TNFi-IR patients¹

RINVOQ® (upadacitinib) - Healthcare Professional Site (3)

RA patients met ACR20 at Week 12 or 14 (Primary Endpoints) and Disease Control through Remission (DAS28-CRP <2.6)^* at Weeks 12 or 14 and observed upto 5 years.^1,3-6

^*Clinical remission does not mean drug-free remission or complete absence of disease activity

Explore the Data

ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; CRP=C-reactive protein; DAS28-CRP=28 joint disease activity score using C-reactive protein

PAYERS COVER RINVOQ

>95%

PREFERRED COMMERCIAL AND MEDICARE PART D COVERAGE^2,*,†

National Commercial and Medicare Part D formulary coverage under the pharmacy benefit as of January 2024.²

*RINVOQ is on a preferred tier or otherwise has preferred status on the plan’s formulary.

†Coverage requirements and benefit designs vary by payer and may change over time. Please consult with payers directly for the most current reimbursem*nt policies.

RINVOQ® (upadacitinib) - Healthcare Professional Site (6)

Explore Now

*RINVOQ is on a preferred tier or otherwise has preferred status on the plan’s formulary.

†Coverage requirements and benefit designs vary by payer and may change over time. Please consult with payers directly for the most current reimbursem*nt policies.

Primary Endpoint Results
(Week 12 or 14)

SELECT-BEYOND: 27% RINVOQ 15 mg + csDMARD vs 11% Placebo + csDMARD^1,8

* P≤0.001 vs RINVOQ vs Placebo or MTX, ^†P=0.0001;Week 1 analyses were not controlled for multiplicity; P‑values obtained through nominal statistical testing.

SELECT‑BEYOND
(Study RA‑V):^1,8
12‑week, randomized, double‑blind, placebo‑controlled study of 499 adult patients with moderate to severe RA who had an inadequate response or intolerance to bDMARDs.

See details

SELECT‑EARLY
(Study RA‑I):^1,9
48‑week, randomized, double‑blind, active comparator‑controlled study of 947 adult patients with moderate to severe RA who were MTX‑naïve.

See details

SELECT‑
MONOTHERAPY (Study RA‑II):^1,3
14‑week, randomized, double‑blind, active comparator‑controlled study of 648 adult patients with moderate to severe RA who had an inadequate response to MTX.

See details

SELECT‑NEXT
(STUDY RA‑III)^1,10
12‑week, randomized, double‑blind, placebo‑controlled study of 661 adult patients with moderate to severe RA who had an inadequate response to csDMARDs.

See details

SELECT‑COMPARE
(Study RA‑IV):^1,11
48‑week, randomized, double‑blind, active comparator‑controlled study of 1629 adult patients with moderate to severe RA who had an inadequate response to MTX.

See details

See Study Details

See ACR Response Criteria

ACR=American College of Rheumatology; bDMARD=biologic disease-modifying antirheumatic drugs; csDMARD=conventional synthetic disease-modifying antirheumatic drugs; IR=intolerance or inadequate response; MTX=methotrexate; NRl=nonresponder imputation; QD=once per day; RA=rheumatoid arthritis; TNFi=tumor necrosis factor inhibitor.

CONTROL THAT'S FAST AND SHOWN TO LAST

RA patients met ACR20 at Week 12 or 14 (Primary Endpoints) and Disease Control through Remission
(DAS28-CRP <2.6)* at Weeks 12 or 14 and observed up to 5 years.^1,3-6

RA patients met ACR20 at Week 12 or 14 (Primary Endpoints) and Disease Control through Remission (DAS28-CRP <2.6)* at Weeks 12 or 14 and observed up to 5 years.^1,3-6

Rapid Remission^1,4

Nearly 1/3 of bDMARD-IR patients achievedremission as early as Week 12 (29% RINVOQ 15mg + csDMARDs (n=164) vs 9% PBO + csDMARDs (n=169) in SELECT-BEYOND)^†

See Remission Data at Weeks 12 and 14

Durable Control^5,6

Remission rates out to 5 years with or without MTX

See Remission Data up to ~5 years

Well-Studied Safety^1,12

>7.5years max. exposure in RA
(~4.2 years median) to RINVOQ 15mg as of 8/15/23^‡

See Safety Profile

*Clinical remission does not mean drug-free remission or complete absence of disease activity

Exceptional Access and Patient Support²

>95%preferred national commercial and Medicare Part D formulary coverage under the pharmacy benefit as of January 2024^2,§,‖
1:1 support to help RA patients start and stay on track with their prescribed treatment plan

^†P<0.001. Analyses were not controlled for multiplicity. P-values obtained through nominal statistical testing.
^‡In PsA: ~5.7 years maximum exposure (~3.7 yearsmedian) to RINVOQ 15mg as of 08/2023. In AS: ~3.8years maximum exposure (~1.7years median) to RINVOQ 15mg as of 08/2023. In nr‑axSpA: ~3.4years maximum exposure (~1 years median) to RINVOQ 15mg as of 08/2023.¹²
^§RINVOQ is on a preferred tier or otherwise has preferred status on the plan's formulary.
^‖Coverage requirements and benefit designs vary by payer and may change over time. Please consult with payers directly for the most current reimbursem*nt policies.

ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biological disease-modifying antirheumatic drug; CRP=C-reactive protein; csDMARDs=conventional synthetic disease modifying antirheumatic drugs; DAS28-CRP=28 joint disease activity score using C-reactive protein; IR=intolerance or inadequate response; max.=maximum; MTX=methotrexate; PBO=placebo; RA=rheumatoid arthritis; TNFi=tumor necrosis factor inhibitor

See how UPADAC Complete provides an exceptional access
and patient support experience

SEE ACCESS & SUPPORT

CLINICAL REMISSION

IMPORTANT SAFETY INFORMATION & INDICATIONS¹

INDICATIONS¹

RINVOQ is indicated for the treatment of:

Moderately to severely active rheumatoid arthritis (RA) in adults who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.
Active psoriatic arthritis (PsA) in adults who have had an inadequate response or intolerance to one or more TNF blockers.
Active ankylosing spondylitis (AS) in adults who have had an inadequate response or intolerance to one or more TNF blockers.
Active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation in adults who have had an inadequate response or intolerance to TNF blocker therapy.

Limitations of Use: RINVOQ is not recommended for use in combination with other Janus kinase (JAK) inhibitors, biologic disease-modifying antirheumatic drugs (bDMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine.

Refractory, moderate to severe atopic dermatitis (AD) in adults and pediatric patients 12 years of age and older whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.

Moderately to severely active ulcerative colitis (UC) in adults who have had an inadequate response or intolerance to one or more TNF blockers.

Moderately to severely active Crohn's disease (CD) in adults who have had an inadequate response or intolerance to one or more TNF blockers.

Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biological therapies for ulcerative colitis or Crohn’s disease, or with potent immunosuppressants such as azathioprine and cyclosporine.

IMPORTANT SAFETY INFORMATION FOR RINVOQ/RINVOQ LQ (upadacitinib)

SERIOUS INFECTIONS

Patients treated with RINVOQ* are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids. If a serious infection develops, interrupt RINVOQ until the infection is controlled.

Reported infections include:

Active tuberculosis (TB), which may present with pulmonary or extrapulmonary disease. Test patients for latent TB before RINVOQ use and during therapy. Consider treatment for latent TB infection prior to RINVOQ use.
Invasive fungal infections, including cryptococcosis and pneumocystosis.
Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.

Carefully consider the risks and benefits of treatment with RINVOQ prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with RINVOQ, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

MORTALITY

In a large, randomized, postmarketing safety study comparing another Janus kinase (JAK) inhibitor with tumor necrosis factor (TNF) blockers in rheumatoid arthritis (RA) patients ≥50 years old with at least one cardiovascular (CV) risk factor, a higher rate of all-cause mortality, including sudden CV death, was observed with the JAK inhibitor. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ.

MALIGNANCIES

Lymphoma and other malignancies have been observed in patients treated with RINVOQ.

In a large, randomized, postmarketing safety study comparing another JAK inhibitor with TNF blockers in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer [NMSC]), lymphomas, and lung cancer (in current or past smokers) was observed with the JAK inhibitor. Patients who are current or past smokers are at additional increased risk.

With RINVOQ, consider the benefits and risks for the individual patient prior to initiating or continuing therapy, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy when on treatment, and patients who are current or past smokers. NMSCs have been reported in patients treated with RINVOQ. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. Advise patients to limit sunlight exposure by wearing protective clothing and using sunscreen.

MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)

In a large, randomized, postmarketing study comparing another JAK inhibitor with TNF blockers in RA patients ≥50 years old with at least one CV risk factor, a higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke) was observed with the JAK inhibitor. Patients who are current or past smokers are at additional increased risk. Discontinue RINVOQ in patients that have experienced a myocardial infarction or stroke.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ, particularly in patients who are current or past smokers and patients with other CV risk factors. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.

THROMBOSIS

In a large, randomized, postmarketing study comparing another JAK inhibitor to TNF blockers in RA patients ≥50 years old with at least one CV risk factor, a higher rate of thrombosis was observed with the JAK inhibitor. Avoid RINVOQ in patients at risk. Patients with symptoms of thrombosis should discontinue RINVOQ and be promptly evaluated.

HYPERSENSITIVITY

RINVOQ is contraindicated in patients with known hypersensitivity to upadacitinib or any of its excipients. Serious hypersensitivity reactions, such as anaphylaxis and angioedema, were reported in patients receiving RINVOQ in clinical trials. If a clinically significant hypersensitivity reaction occurs, discontinue RINVOQ and institute appropriate therapy.

GASTROINTESTINAL PERFORATIONS

Gastrointestinal (GI) perforations have been reported in clinical trials with RINVOQ. Monitor RINVOQ-treated patients who may be at risk for GI perforation (e.g., patients with a history of diverticulitis and patients taking NSAIDs or corticosteroids). Promptly evaluate patients presenting with new onset abdominal pain for early identification of GI perforation.

LABORATORY ABNORMALITIES

Neutropenia

Treatment with RINVOQ was associated with an increased incidence of neutropenia (absolute neutrophil count [ANC] <1000 cells/mm³). Treatment with RINVOQ is not recommended in patients with an ANC <1000 cells/mm³. Evaluate neutrophil counts at baseline and thereafter according to routine patient management.

Lymphopenia

Absolute lymphocyte counts (ALC) <500 cells/mm³ were reported in RINVOQ-treated patients. Treatment with RINVOQ is not recommended in patients with an ALC <500 cells/mm³. Evaluate at baseline and thereafter according to routine patient management.

Anemia

Decreases in hemoglobin levels to <8 g/dL were reported in RINVOQ-treated patients. Treatment should not be initiated or should be interrupted in patients with hemoglobin levels <8 g/dL. Evaluate at baseline and thereafter according to routine patient management.

Lipids

Treatment with RINVOQ was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. Manage patients according to clinical guidelines for the management of hyperlipidemia. Evaluate patients 12 weeks after initiation of treatment and thereafter according to the clinical guidelines for hyperlipidemia.

Liver enzyme elevations

Treatment with RINVOQ was associated with increased incidence of liver enzyme elevation compared to placebo. Evaluate at baseline and thereafter according to routine patient management. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. If increases in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) are observed during routine patient management and drug-induced liver injury is suspected, RINVOQ should be interrupted until this diagnosis is excluded.

EMBRYO-FETAL TOXICITY

Based on findings in animal studies, RINVOQ may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RINVOQ and for 4 weeks after the final dose. Verify pregnancy status of females of reproductive potential prior to starting treatment with RINVOQ.

VACCINATION

Avoid use of live vaccines during, or immediately prior to, RINVOQ therapy. Prior to initiating RINVOQ, patients should be brought up to date on all immunizations, including prophylactic varicella zoster or herpes zoster vaccinations, in agreement with current immunization guidelines.

MEDICATION RESIDUE IN STOOL

Reports of medication residue in stool or ostomy output have occurred in patients taking RINVOQ. Most reports described anatomic or functional GI conditions with shortened GI transit times. Instruct patients to contact their healthcare provider if medication residue is observed repeatedly. Monitor patients clinically and consider alternative treatment if there is an inadequate therapeutic response.

LACTATION

There are no data on the presence of RINVOQ in human milk, the effects on the breastfed infant, or the effects on milk production. Available data in animals have shown the excretion of RINVOQ in milk. Advise patients that breastfeeding is not recommended during treatment with RINVOQ and for 6 days after the last dose.

HEPATIC IMPAIRMENT

RINVOQ is not recommended for use in patients with severe hepatic impairment.

ADVERSE REACTIONS

The most common adverse reactions in RINVOQ clinical trials were upper respiratory tract infections, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, headache, increased blood creatine phosphokinase, hypersensitivity, folliculitis, abdominal pain, increased weight, influenza, fatigue, neutropenia, myalgia, influenza-like illness, elevated liver enzymes, rash, and anemia.

Inform patients that retinal detachment has been reported in clinical trials with RINVOQ. Advise patients to immediately inform their healthcare provider if they develop any sudden changes in vision while receiving RINVOQ.

Dosage Forms and Strengths: RINVOQ is available in 15 mg, 30 mg, and 45 mg extended-release tablets. RINVOQ LQ is available in a 1 mg/mL oral solution.

*Unless otherwise stated, “RINVOQ” in the IMPORTANT SAFETY INFORMATION refers to RINVOQ and RINVOQ LQ.

US-RNQ-240118

Please see full Prescribing Information.

REFERENCES

RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
Data on File, AbbVie Inc. January 2024.
Smolen JS, Pangan AL, Emery P, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet. 2019;393(10188):2303-2311.
Data on File. ABVRRTI72945.
Smolen JS, Emery P, Rigby W, et al. Upadacitinib as monotherapy in patients with rheumatoid arthritis and prior inadequate response to methotrexate: results at 260 weeks from the SELECT-MONOTHERAPY study. Poster presented at: The European Congress of Rheumatology, 31 May - 3 June 2023, Milan, Italy.
Fleischmann R, Bessette L, Sparks J et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response or intolerance to biologic DMARDs: results through 5 years from the SELECT-BEYOND study. Poster presented at: the American College of Rheumatology Convergence, November 10-14, 2022, Philadelphia, PA, USA.
Data on File. ABVRRTI68885.
Genovese MC, Fleischmann R, Combe B, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2513-2524.
van Vollenhoven R, Takeuchi T, Pangan AL, et al. Efficacy and safety of upadacitinib monotherapy in methotrexate-naïve patients with moderately to severely active rheumatoid arthritis (SELECT-EARLY): a randomized, double-blind, active-comparator, multi-center, multi-country trial. Arthritis & Rheumatol. 2020. doi:10.1002/art.41384.
Burmester GR, Kremer JM, Van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10139):2503-2512.
Fleischmann R, Pangan AL, Song I-H, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase 3, double-blind, randomized controlled trial. Arthritis Rheumatol. 2019;71(11):1788-1800.
Data on File. ABVRRTI77110.

RA patients met ACR20 at Week 12 or 14 (Primary Endpoints) and Disease Control through Remission
(DAS28-CRP <2.6)* at Weeks 12 or 14 and observed up to 5 years. Explore the Data

RA patients met ACR20 at Week 12 or 14 (Primary Endpoints) and Disease Control through Remission (DAS28-CRP <2.6)* at Weeks 12 or 14 and observed up to 5 years. Explore the Data

*Clinical remission does not mean drug-free remission or complete absence of disease activity

Clinical Remission

Remission + LDA at Weeks 12 and 14

Remission out to ~5 years

LDA out to ~5 years

Safety Profile

Data Up to 12 Months

Long-term Exposure Data

Important Safety Information

Commercial Access

RINVOQ Complete

How To Enroll Patients

Downloadable Resources

Dosing

Monitoring

Mechanism of Action

ACR response criteria incorporate physician and patient assessments, as well as acute inflammatory, pain, and physical function measures.

References

1. Felson DT, Anderson JJ, Boers M, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. ArthritisRheum. 1993;36(6):729-740.
2. Uhlig T, Haavardsholm EA, Kvien TK. Comparison of the Health Assessment Questionnaire (HAQ) and the modified HAQ (MHAQ) in patients with rheumatoid arthritis. Rheumatology. 2006;45(4):454‑458.

US-MULT-220500

SELECT-CHOICE

Adults with moderately to severely active RA and inadequate response or intolerance to bDMARDs.¹
RINVOQ is indicated for TNFi-IR patients

^aAfter the initial dose, active comparator^® IV was administered at 2 and 4 weeks, then every 4 weeks thereafter. The last dose occurred at Week 20. Weight‑based dosing was as follows: <60 kg: 500 mg; 60 - 100 kg: 750 mg; >100 kg: 1000 mg.²
^bStarting at Week 12, patients who did not achieve ≥20% improvement in both TJC and SJC compared to baseline at 2 consecutive visits were to have background medication(s) (corticosteroids, NSAIDs, acetaminophen or adding or increasing doses in csDMARD(s)) adjusted or added.^1,3

Primary Endpoint¹

Change from baseline DAS28‑CRP at Week12 (noninferiority) against a margin of 0.6

DATA LIMITATIONS

Data not labeled as a ranked secondary endpoint were prespecified nonranked endpoints not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.

Baseline Characteristics¹

*Did not receive any of the protocol-specified bDMARDs prior to entry.
^†Based on prednisone equivalent.

ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biological disease-modifying anti-rheumatic drug; CDAI=clinical disease activity index; CR=clinical remission; CRP=C-reactive protein; DAS28-CRP=28 joint disease score using C-reactive protein; DAS28-ESR=28 joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; EULAR=European League Against Rheumatism; IV=intravenous; LDA=low disease activity; QD=once per day; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF-36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints

REFERENCES

1. Rubbert‑Roth A, Enejosa J, Pangan AL, et al. Efficacy and Safety of Upadacitinib vs Abatacept in Patients With Active Rheumatoid Arthritis and Prior Inadequate Response or Intolerance to Biologic Disease‑Modifying Anti‑Rheumatic Drugs (SELECT‑CHOICE): A Double‑Blind, Randomized Controlled Phase 3 Trial. Poster presented at: The European Congress of Rheumatology, 3‑6June2020, E‑Congress.
2. Rubbert-Roth A, Enejosa J, Pangan AL, et al. Efficacy and Safety of Upadacitinib vs Abatacept in Patients with Active Rheumatoid Arthritis and Prior Inadequate Response or Intolerance to Biologic Disease‑Modifying Anti‑Rheumatic Drugs (SELECT‑CHOICE): A Double‑Blind, Randomized Controlled Phase3 Trial. Ann Rheum Dis 2020,79(Supp1):1011.
3. Data on File. ABVRRTI70957.
4. Data on File. ABVRRTI71850.

US-MULT-220500

SELECT-COMPARE

Adults with moderately to severely active RA who had an inadequate response to MTX¹
RINVOQ is indicated for TNFi-IR patients

^aX-ray imaging was performed at these time points; Week 14 for non-responder patients, who were rescued.^2,3
^bRescue criteria: At Weeks 14, 18 and 22 if <20% improvement in TJC and SJC vs baseline; at Week 26 all remaining PBO patients were switched to RINVOQ, and patients receiving RINVOQ or active comparator were switched to active comparator or RINVOQ, respectively, if CDAI>10.²
^cStarting at Week 26, initiation or change in background RA medication(s) including corticosteroids, NSAIDs, or acetaminophen was permitted.⁴
^dStarting at Week 48, patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.⁵
^eAt Week 48, initiation or change in csDMARDs was allowed, however not all patients received background MTX.⁵
^fPatients continued treatment with UPA or active comparator in a blinded manner until the last patient completed the Week 48 visit and received open-label treatment thereafter.⁸

PRIMARY ENDPOINT¹

ACR20 response: RINVOQ 15 mg + MTX vs Placebo + MTX at Week 12

SELECT RANKED SECONDARY ENDPOINTS²

At Week 12 vs Placebo + MTX:

Change from baseline in DAS28-CRP
Change from baseline in HAQ-DI
Change from baseline in SF-36 (PCS)
Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
Proportion of patients achieving DAS28-CRP<2.6 (CR)

At Week 26 vs Placebo + MTX:

Change from baseline mTSS

SELECT PRESPECIFIED NONRANKED ENDPOINTS^3,9,10

ACR20/50/70 response rates and change from baseline in individual ACR components at all visits (except those that were ranked timepoints).
Proportion of patients achieving CR based on DAS28-CRP, DAS28-ESR, SDAI, CDAI, and Boolean criteria at all visits (except those that were ranked timepoints).
Proportion of patients with no radiographic progression (mTSS ≤0) atWeek 26, Week 48, and Week96.
Change from baseline in mTSS at Week 26, Week 48, and Week96.
Change from baseline in joint space narrowing score and joint erosion score at Week 26, Week 48, and Week96.

DATA LIMITATIONS

Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.

SELECT-COMPARE was not designed to evaluate the efficacy of active comparator + MTX vs Placebo + MTX. No conclusions regarding this comparison can be made.

BASELINE CHARACTERISTICS^3,11

*Based on prednisone equivalent

ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARDs=biologic disease‑modifying antirheumatic drugs; CDAI=clinical disease activity index; CR=clinical remission; CRP=C‑reactive protein; DAS28-CRP=28 joint disease activity score using C-reactive protein; DAS28-ESR=28 joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C‑reactive protein; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; PBO=Placebo; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once per day; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; VAS=visual analog scale

REFERENCES

1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Fleischmann R, Pangan AL, Song I-H, et al. Supplement - Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, double‑blind, randomized controlled trial. Arthritis Rheumatol. 2019;71(11):1788‑1800.
3. Fleischmann R, Pangan AL, Song I-H, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, double‑blind, randomized controlled trial. ArthritisRheumatol. 2019;71(11):1788‑1800.
4. Data on File. ABVRRTI70534.
5.Data on File. ABVRRTI70955.
6.Data on File. ABVRRTI68439.
7.Upadacitinib meets all primary and ranked secondary endpoints including superiority versus adalimumab in phase 3 study in rheumatoid arthritis. AbbVie Inc. https://news.abbvie.com/news/upadacitinib-meets-all-primary-and-ranked-secondary-endpoints-including-superiority-versus-adalimumab-in-phase-3-study-in-rheumatoid-arthritis.htm. April9,2018. August15,2019.
8.Fleishmann R, Mysler E, Bessette L, et al. Long-term safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis results at 3 years from the SELECT-COMPARE study. Poster presented at: the American College of Rheumatology Convergence, 5-9 November 2021. E-Congress.
9.Data On File. ABVRRTI68440.
10.Data on File. ABVRRTI70956.
11.Fleischmann R, Pangan AL, Mysler E, et al. A phase3, randomized, double‑blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate. Oral presentation at: The ACR annual meeting 2018, 19–24October2018, Chicago, USA.

US-MULT-220500

SELECT-MONOTHERAPY

Adults with moderately to severely active RA who had an inadequate response to MTX¹
RINVOQ is indicated for TNFi-IR patients

Upadacitinib 30mg is not an approved dose.

^aPatients on MTX were randomized to receive either RINVOQ 15 mg or upadacitinib 30 mg at Week 14.³

^bStarting at Week 26, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDS, acetaminophen or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.⁵

^cFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD including those previously on UPA 30 mg.⁷

Primary Endpoint¹

ACR20 response at Week 14

Select Ranked Secondary Endpoints^3,6

At Week 14:

Change from baseline in DAS28-CRP
Change from baseline in HAQ-DI
Change from baseline in SF-36 (PCS)
Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
Proportion of patients achieving DAS28-CRP<2.6 (CR)

SELECT PRESPECIFIED NONRANKED ENDPOINTS^3,6

ACR50 and ACR70 response at Week 14
Proportion of patients achieving CR based on DAS28‑CRP <2.6, DAS28-ESR <2.6, SDAI ≤3.3, CDAI ≤2.8, and Boolean criteria at all visits (except those that were ranked timepoints)

Data Limitations

Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.

Baseline Characteristics³

*Prior to receiving study drug. In the control arm, patients continued prior MTX dose as blinded study drug.
^†Prednisone equivalent

ACPA=anti‑citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=clinical disease activity index; cMTX=continuous methotrexate; csDMARDs=conventional synthetic disease‑modifying antirheumatic drugs; CR=clinical remission; CRP=C‑reactive protein; DAS28-CRP=28 joint disease activity score using C-reactive protein; DAS28-ESR=28 joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C‑reactive protein; LDA=low disease activity; MTX=methotrexate; NSAIDs=nonsteroidal anti‑inflammatory drugs; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; VAS=visual analog scale

REFERENCES

1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Smolen JS, Pangan AL, Emery P, et al. Supplement - Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT‑MONOTHERAPY): a randomised, placebo‑controlled, double‑blind phase 3 study. Lancet. 2019;393(10188):2‍3‍0‍3⁠-⁠2⁠3⁠1⁠1⁠.
3. Smolen JS, Pangan AL, Emery P, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT‑MONOTHERAPY): a randomised, placebo‑controlled, double‑blind phase 3 study. Lancet. 2019;393(10188):2‍3‍0‍3‍⁠⁠-⁠2⁠3⁠1⁠1⁠.
4. Smolen JS, Emery P, Rigby W, et al. Upadacitinib as monotherapy in patients with rheumatoid arthritis: results at 48 weeks from the SELECT‑MONOTHERAPY study. Poster presented at: The European Congress of Rheumatology, 12‑15June2019, Madrid, Spain.
5. Data on File. ABVRRTI68979.
6. Data on File. ABVRRTI68841.
7. A study comparing upadacitinib (ABT-494) monotherapy to methotrexate (MTX) monotherapy in adults with rheumatoid arthritis (RA) who have an inadequate response to MTX (SELECT-MONOTHERAPY). ClinicalTrials.gov identifier: NCT02706951. https://clinicaltrials.gov/ct2/show/NCT02706951. Updated August 2, 2021. Accessed November 30, 2021.

US-MULT-220500

SELECT‑EARLY

Adults with moderately to severely active RA who were MTX‑naïve¹
RINVOQ is indicated for TNFi-IR patients

Upadacitinib 30mg is not an approved dose.

^aInitially 947 patients were randomized in the study, but two patients were never dosed.²
^bX-ray images of hands and feet obtained at these time points.²
^cStarting at Week12, patients with ≤20% improvement in TJC and SJC compared to baseline at two consecutive visits continued blinded therapy and optimized background RA medications (corticosteroids, NSAIDs, and/or low‑potency analgesics).^3,4
^dAt Week 26, patients with CDAI≤2.8 continued their original study drug; background medications (NSAIDs, corticosteroids, and/or low‑potency analgesics, and csDMARDs) were optimized in patients with CDAI>2.8 but ≥20% improvement in TJC and SJC; among patients with CDAI >2.8 and <20% improvement in TJC and SJC, RINVOQ 15 mg or upadacitinib 30 mg were added by re‑randomization according to 1:1 ratio for those initially randomized to MTX, and MTX was added for those initially randomized to RINVOQ 15 mg or upadacitinib 30 mg.^2,5
^eStarting at Week 48, patients who did not achieve ≥ 20% improvement in both TJC and SJC at two consecutive visits were removed from the study. Initiation of or change in background RA medications (NSAIDs, corticosteroids, low potency analgesics, and csDMARDs; not all patients received background MTX) is allowed at anytime during Period 2.⁶
^fFollowing a protocol amendment, all patients in the long-term extension who were previously receiving UPA 30 mg received UPA 15 mg.¹¹

Primary Endpoint¹

ACR50 response at Week 12

Ranked Secondary Endpoints^3,8

At Week 12:

Change from baseline in DAS28-CRP
Change from baseline in HAQ-DI
Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
Change from baseline in SF-36 (PCS)

At Week 24:

Change from baseline in mTSS
Proportion of patients achieving DAS28-CRP<2.6 (CR)

Select prespecified
nonranked endpoints^2,3,9,10

ACR20/50/70 at all visits (except those that were ranked timepoints)
Change from baseline in mTSS at Week24, Week48, and Week96
Proportion of patients with no radiographic progression (mTSS ≤0) at Week 24, Week 48, and Week96
Change from baseline in JE and JSN score at Week24, Week48, and Week96

Data Limitations

Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.

Baseline Characteristics³

*Prednisone equivalent dose in patients receiving oral glucocorticoids at baseline.

ACPA = anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=clinical disease activity index; CR=clinical remission; CRP=C reactive protein; csDMARDs=conventional synthetic disease-modifying antirheumatic drugs; DAS28-CRP=28 joint disease activity score using C-reactive protein; HAQ-DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C-reactive protein; JE=joint erosion score; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAIDs=nonsteroidal anti-inflammatory drugs; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF-36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; VAS=visual analog scale

REFERENCES

1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Van Vollenhoven R, Takeuchi T, Pangan AL, et al. Supplement: Efficacy and safety of upadacitinib monotherapy in methotrexate‑naïve patients with moderately to severely active rheumatoid arthritis (SELECT‑EARLY): a randomized, double-blind, active‑comparator, multi‑center, multi‑country trial. Arthritis Rheumatol. 2020. doi:10.1002/art.41384.
3. Van Vollenhoven R, Takeuchi T, Pangan AL, et al. Efficacy and safety of upadacitinib monotherapy in methotrexate‑naïve patients with moderately to severely active rheumatoid arthritis (SELECT‑EARLY): a randomized, double‑blind, active‑comparator, multi-center, multi‑country trial. Arthritis Rheumatol. 2020. doi:10.1002/art.41384.
4. Data on File. ABVRRTI70661.
5. Data on File. ABVRRTI68563.
6. Data on File. ABVRRTI70953.
7. Van Vollenhoven R, Takeuchi T, Rischmueller M, et al. Upadacitinib monotherapy in methotrexate‑naïve patients with rheumatoid arthritis: results at 72weeks from SELECT‑EARLY. Poster presented at: The European Congress of Rheumatology, 3‑6 June 2020, E-Congress.
8. Data on File. ABVRRTI68564.
9. Data on File. ABVRRTI70539.
10. Data on File. ABVRRTI70954.
11. A study to compare upadacitinib (ABT-494) monotherapy to methotrexate (MTX) monotherapy in adults with rheumatoid arthritis (RA) who have not previously taken methotrexate (SELECT-EARLY). ClinicalTrials.gov identifier: NCT02706873. https://clinicaltrials.gov/ct2/show/NCT02706873. Updated August 2, 2021. Accessed November 30, 2021.

US-MULT-220500

SELECT-NEXT

Adults with moderately to severely active RA who had an inadequate response to csDMARD(s)¹
RINVOQ is indicated for TNFi-IR patients

Upadacitinib 30mg is not an approved dose.

^aStarting at Week 24, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDS, acetaminophen or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.⁴
^bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.⁷

Primary Endpoint¹

ACR20 response at Week 12

Select Ranked Secondary Endpoints^5,6

At Week 12:

Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
Proportion of patients achieving DAS28-CRP<2.6 (CR)
Proportion of patients achieving CDAl≤10 (LDA)

Select Prespecified nonranked endpoints⁶

ACR50 and ACR70 response at Week 12
ACR20 response at Week 1

Data Limitations

Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.

Baseline Characteristics⁵

*Based on prednisone equivalent

ACPA=anti‑citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD= biologic disease‑modifying antirheumatic drug; CDAI=clinical disease activity index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease-modifying anti-rheumatic drug; DAS28-CRP=28 joint disease activity score using C-reactive protein; HAQ-DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C-reactive protein; LDA=low disease activity; MTX=methotrexate; NSAIDs=nonsteroidal anti‑inflammatory drugs; PBO=placebo; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; VAS=visual analog scale.

REFERENCES

1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Burmester GR, Kremer JM, Van den Bosch F, et al. Supplement - Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease‑modifying anti‑rheumatic drugs (SELECT‑NEXT): a randomised, double‑blind, placebo‑controlled phase 3 trial. Lancet. 2018;391(10139):2503‑2512. 
3. Burmester GR, Van den Bosch F, Bessette L, et al. Long‑term safety and efficacy of upadacitinib in patients with rheumatoid arthritis and an inadequate response to csDMARDs: results at 60 weeks from the SELECT‑NEXT study. Poster presented at: The European Congress of Rheumatology, 12‑15June 2019, Madrid, Spain.
4. Data on File. ABVRRTI68981.
5.Burmester GR, Kremer JM, Van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease‑modifying anti‑rheumatic drugs (SELECT‑NEXT): a randomised, double‑blind, placebo‑controlled phase 3 trial. Lancet. 2018;391(10139):2‍5‍0‍3‍‑2‍5‍1‍2‍.
6. Data on File. ABVRRTI68843.
7. Data On File. ABVRRTI73233.

US-MULT-220500

SELECT-BEYOND

Adults with moderately to severely active RA who had an inadequate response or intolerance to bDMARDs¹
RINVOQ is indicated for TNFi-IR patients

Upadacitinib 30mg is not an approved dose.

^aStarting at Week 24, initiation of or change in corticosteroids, NSAIDs, acetaminophen, and csDMARDs was permitted. Patients not achieving response criteria ≥20% improvement in SJC and TJC at two consecutive visits were removed from the study.^4,5

^bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD including those previously on UPA 30 mg.⁸

Primary Endpoint¹

ACR20 response at Week 12

Ranked Secondary Endpoints^6,7

At Week 12:

Change from baseline in DAS28-CRP
Change from baseline in HAQ-DI
Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
Change from baseline in SF-36 (PCS)

Select Prespecified nonranked endpoints⁷

ACR20, ACR50 and ACR70 response at all visits (except those that were ranked timepoints)
ACR20 response at Week 1
Proportion of patients achieving CR based on DAS28‑CRP, DAS28‑ESR, SDAI, and CDAI at all visits
Proportion of patients achieving Boolean criteria at Week12

Data Limitations

Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.

Baseline Characteristics⁶

*Oral or parenteral methotrexate (7.5-25 mg per week).
^†Data available for 168 patients receiving placebo and 161 patients receiving RINVOQ 15 mg.
^‡All combinations allowed except MTX and leflunomide.
^§Mean MTX dose calculated only for patients receiving MTX.
^‖Based on prednisone equivalent.

ACPA=anti‑citrullinated protein antibodies; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARDs=biologic disease‑modifying antirheumatic drugs; CDAI=clinical disease activity index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease‑modifying antirheumatic drug; DAS28-CRP=28 joint disease activity score using C-reactive protein; DAS28-ESR=28 joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; hsCRP=high‑sensitivity C‑reactive protein; HAQ‑DI=health assessment questionnaire disability index; IL-6=interleukin 6; LDA=low disease activity; MTX=methotrexate; NSAIDs=nonsteroidal anti‑inflammatory drugs; PBO=placebo; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF‑36 (PCS)=36‑item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; VAS=visual analog scale

REFERENCES

1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Genovese MC, Fleischmann R, Combe B, et al. Supplement - Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease‑modifying anti‑rheumatic drugs (SELECT‑BEYOND): a double‑blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2‍5‍1‍3‍‍‑‍2‍5‍2‍4‍.
3. Genovese MC, Combe B, Hall S, et al. Upadacitinib in patients with rheumatoid arthritis and inadequate response or intolerance to biologic DMARDs: results at 60 weeks from the SELECT‑BEYOND Study. Poster presented at: The European Congress of Rheumatology, 12‑15June2019, Madrid, Spain.
4. Data on File. ABVRRTI68669.
5. Data on File. ABVRRTI68670.
6. Genovese MC, Fleischmann R, Combe B, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease‑modifying anti‑rheumatic drugs (SELECT‑BEYOND): a double‑blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2‍5‍1‍3‍‍‑‍2‍5‍2‍4‍.
7. Data on File. ABVRRTI68842.
8. A study to compare upadacitinib (ABT-494) to placebo in adults with rheumatoid arthritis on stable dose of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) with an inadequate response or intolerance to biologic DMARDs (SELECT-BEYOND). ClinicalTrials.gov identifier: NCT02706847. https://clinicaltrials.gov/ct2/show/NCT02706847. Updated August 2, 2021. Accessed November 30, 2021.

US-MULT-220500

IMPORTANT SAFETY INFORMATION & INDICATION FOR HUMIRA®(adalimumab)¹

INDICATION¹

HUMIRA is indicated, alone or in combination with methotrexate or other non-biologic DMARDs, for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis.

IMPORTANT SAFETY INFORMATION¹

SERIOUS INFECTIONS

Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Discontinue HUMIRA if a patient develops a serious infection or sepsis.

Reported infections include:

Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before HUMIRA use and during therapy. Initiate treatment for latent TB prior to HUMIRA use.
Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

Carefully consider the risks and benefits of treatment with HUMIRA prior to initiating therapy in patients: 1. with chronic or recurrent infection, 2. who have been exposed to TB, 3. with a history of opportunistic infection, 4. who resided in or traveled in regions where mycoses are endemic, 5. with underlying conditions that may predispose them to infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with HUMIRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

Do not start HUMIRA during an active infection, including localized infections.
Patients older than 65 years, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants may be at greater risk of infection.
If an infection develops, monitor carefully and initiate appropriate therapy.
Drug interactions with biologic products: A higher rate of serious infections has been observed in RA patients treated with rituximab who received subsequent treatment with a TNF blocker. An increased risk of serious infections has been seen with the combination of TNF blockers with anakinra or abatacept, with no demonstrated added benefit in patients with RA. Concomitant administration of HUMIRA with other biologic DMARDs (e.g., anakinra or abatacept) or other TNF blockers is not recommended based on the possible increased risk for infections and other potential pharmacological interactions.

MALIGNANCY

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including HUMIRA. Postmarketing cases of hepatosplenic T‑cell lymphoma (HSTCL), a rare type of T‑cell lymphoma, have been reported in patients treated with TNF blockers, including HUMIRA. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants.

Consider the risks and benefits of HUMIRA treatment prior to initiating or continuing therapy in a patient with known malignancy.
In clinical trials, more cases of malignancies were observed among HUMIRA-treated patients compared to control patients.
Non-melanoma skin cancer (NMSC) was reported during clinical trials for HUMIRA-treated patients. Examine all patients, particularly those with a history of prolonged immunosuppressant or PUVA therapy, for the presence of NMSC prior to and during treatment with HUMIRA.
In HUMIRA clinical trials, there was an approximate 3-fold higher rate of lymphoma than expected in the general U.S. population. Patients with chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at higher risk of lymphoma than the general population, even in the absence of TNF blockers.
Postmarketing cases of acute and chronic leukemia were reported with TNF blocker use. Approximately half of the postmarketing cases of malignancies in children, adolescents, and young adults receiving TNF blockers were lymphomas; other cases included rare malignancies associated with immunosuppression and malignancies not usually observed in children and adolescents.

HYPERSENSITIVITY

Anaphylaxis and angioneurotic edema have been reported following HUMIRA administration. If a serious allergic reaction occurs, stop HUMIRA and institute appropriate therapy.

HEPATITIS B VIRUS REACTIVATION

Use of TNF blockers, including HUMIRA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases have been fatal.
Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF blocker therapy.
Exercise caution in patients who are carriers of HBV and monitor them during and after HUMIRA treatment.
Discontinue HUMIRA and begin antiviral therapy in patients who develop HBV reactivation. Exercise caution when resuming HUMIRA after HBV treatment.

NEUROLOGIC REACTIONS

TNF blockers, including HUMIRA, have been associated with rare cases of new onset or exacerbation of central nervous system and peripheral demyelinating diseases, including multiple sclerosis, optic neuritis, and Guillain-Barré syndrome.
Exercise caution when considering HUMIRA for patients with these disorders; discontinuation of HUMIRA should be considered if any of these disorders develop.
There is a known association between intermediate uveitis and central demyelinating disorders.

HEMATOLOGIC REACTIONS

Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia has been infrequently reported with HUMIRA.
Consider stopping HUMIRA if significant hematologic abnormalities occur.

CONGESTIVE HEART FAILURE

Worsening and new onset congestive heart failure (CHF) has been reported with TNF blockers. Cases of worsening CHF have been observed with HUMIRA; exercise caution and monitor carefully.

AUTOIMMUNITY

Treatment with HUMIRA may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.

IMMUNIZATIONS

Patients on HUMIRA should not receive live vaccines.
Pediatric patients, if possible, should be brought up to date with all immunizations before initiating HUMIRA therapy.
Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant. The safety of administering live or live-attenuated vaccines in infants exposed to HUMIRA in utero is unknown. Risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants.

ADVERSE REACTIONS

The most common adverse reactions in HUMIRA clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash.

Please see full Prescribing Information

Reference: 1. HUMIRA Injection [package insert]. North Chicago, IL: AbbVie Inc.

US-MULT-200095

SELECT-BEYOND

Adults with moderately to severely active RA who had an inadequate response or intolerance to bDMARDs¹
RINVOQ is indicated for TNFi-IR patients

Upadacitinib 30mg is not an approved dose.

^bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD including those previously on UPA 30 mg.⁸

Primary Endpoint¹

ACR20 response at Week 12

Ranked Secondary Endpoints^6,7

At Week 12:

Change from baseline in DAS28-CRP
Change from baseline in HAQ-DI
Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
Change from baseline in SF-36 (PCS)

Select Prespecified nonranked endpoints⁷

ACR20, ACR50 and ACR70 response at all visits (except those that were ranked timepoints)
ACR20 response at Week 1
Proportion of patients achieving CR based on DAS28‑CRP, DAS28‑ESR, SDAI, and CDAI at all visits
Proportion of patients achieving Boolean criteria at Week12

Data Limitations

Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.

Baseline Characteristics⁶

REFERENCES

US-MULT-220500

SELECT‑EARLY

Adults with moderately to severely active RA who were MTX‑naïve¹
RINVOQ is indicated for TNFi-IR patients

Upadacitinib 30mg is not an approved dose.

Primary Endpoint¹

ACR50 response at Week 12

Ranked Secondary Endpoints^3,8

At Week 12:

Change from baseline in DAS28-CRP
Change from baseline in HAQ-DI
Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
Change from baseline in SF-36 (PCS)

At Week 24:

Change from baseline in mTSS
Proportion of patients achieving DAS28-CRP<2.6 (CR)

Select prespecified
nonranked endpoints^2,3,9,10

ACR20/50/70 at all visits (except those that were ranked timepoints)
Change from baseline in mTSS at Week24, Week48, and Week96
Proportion of patients with no radiographic progression (mTSS ≤0) at Week 24, Week 48, and Week96
Change from baseline in JE and JSN score at Week24, Week48, and Week96

Data Limitations

Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.

Baseline Characteristics³

*Prednisone equivalent dose in patients receiving oral glucocorticoids at baseline.

ACPA = anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=clinical disease activity index; CR=clinical remission; CRP=C reactive protein; csDMARDs=conventional synthetic disease-modifying antirheumatic drugs; DAS28-CRP=28 joint disease activity score using C-reactive protein; HAQ-DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C-reactive protein; JE=joint erosion score; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAIDs=nonsteroidal anti-inflammatory drugs; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF-36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; VAS=visual analog scale

REFERENCES

US-MULT-220500

SELECT-MONOTHERAPY

Adults with moderately to severely active RA who had an inadequate response to MTX¹
RINVOQ is indicated for TNFi-IR patients

Upadacitinib 30mg is not an approved dose.

^aPatients on MTX were randomized to receive either RINVOQ 15 mg or upadacitinib 30 mg at Week 14.³

^cFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD including those previously on UPA 30 mg.⁷

Primary Endpoint¹

ACR20 response at Week 14

Select Ranked Secondary Endpoints^3,6

At Week 14:

Change from baseline in DAS28-CRP
Change from baseline in HAQ-DI
Change from baseline in SF-36 (PCS)
Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
Proportion of patients achieving DAS28-CRP<2.6 (CR)

SELECT PRESPECIFIED NONRANKED ENDPOINTS^3,6

ACR50 and ACR70 response at Week 14
Proportion of patients achieving CR based on DAS28‑CRP <2.6, DAS28-ESR <2.6, SDAI ≤3.3, CDAI ≤2.8, and Boolean criteria at all visits (except those that were ranked timepoints)

Data Limitations

Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.

Baseline Characteristics³

*Prior to receiving study drug. In the control arm, patients continued prior MTX dose as blinded study drug.
^†Prednisone equivalent

REFERENCES

US-MULT-220500

SELECT-NEXT

Adults with moderately to severely active RA who had an inadequate response to csDMARD(s)¹
RINVOQ is indicated for TNFi-IR patients

Upadacitinib 30mg is not an approved dose.

Primary Endpoint¹

ACR20 response at Week 12

Select Ranked Secondary Endpoints^5,6

At Week 12:

Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
Proportion of patients achieving DAS28-CRP<2.6 (CR)
Proportion of patients achieving CDAl≤10 (LDA)

Select Prespecified nonranked endpoints⁶

ACR50 and ACR70 response at Week 12
ACR20 response at Week 1

Data Limitations

Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.

Baseline Characteristics⁵

*Based on prednisone equivalent

ACPA=anti‑citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD= biologic disease‑modifying antirheumatic drug; CDAI=clinical disease activity index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease-modifying anti-rheumatic drug; DAS28-CRP=28 joint disease activity score using C-reactive protein; HAQ-DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C-reactive protein; LDA=low disease activity; MTX=methotrexate; NSAIDs=nonsteroidal anti‑inflammatory drugs; PBO=placebo; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; VAS=visual analog scale.

REFERENCES

US-MULT-220500

SELECT-COMPARE

Adults with moderately to severely active RA who had an inadequate response to MTX¹
RINVOQ is indicated for TNFi-IR patients

PRIMARY ENDPOINT¹

ACR20 response: RINVOQ 15 mg + MTX vs Placebo + MTX at Week 12

SELECT RANKED SECONDARY ENDPOINTS²

At Week 12 vs Placebo + MTX:

Change from baseline in DAS28-CRP
Change from baseline in HAQ-DI
Change from baseline in SF-36 (PCS)
Proportion of patients achieving DAS28-CRP≤3.2 (LDA)
Proportion of patients achieving DAS28-CRP<2.6 (CR)

At Week 26 vs Placebo + MTX:

Change from baseline mTSS

SELECT PRESPECIFIED NONRANKED ENDPOINTS^3,9,10

ACR20/50/70 response rates and change from baseline in individual ACR components at all visits (except those that were ranked timepoints).
Proportion of patients achieving CR based on DAS28-CRP, DAS28-ESR, SDAI, CDAI, and Boolean criteria at all visits (except those that were ranked timepoints).
Proportion of patients with no radiographic progression (mTSS ≤0) atWeek 26, Week 48, and Week96.
Change from baseline in mTSS at Week 26, Week 48, and Week96.
Change from baseline in joint space narrowing score and joint erosion score at Week 26, Week 48, and Week96.

DATA LIMITATIONS

Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.

SELECT-COMPARE was not designed to evaluate the efficacy of active comparator + MTX vs Placebo + MTX. No conclusions regarding this comparison can be made.

BASELINE CHARACTERISTICS^3,11

*Based on prednisone equivalent

REFERENCES

US-MULT-220500

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On January 14, 2022, the Prescribing Information and Medication Guide for RINVOQ (upadacitinib) was updated to include a new Indication, Recommended Dosage information and added a Contraindication related to Hypersensitivity and a new Warning and Precaution for Hypersensitivity Reactions.

The relevant sections of the Prescribing Information read as follows:

1 INDICATION AND USAGE

Section 1.3 Atopic Dermatitis

RINVOQ is indicated for the treatment of adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies are inadvisable.

Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants.

2 DOSAGE AND ADMINISTRATION

2.5 Recommended Dosage in Atopic Dermatitis

Pediatric Patients 12 Years of Age and Older Weighing at Least 40 kg and Adults Less Than 65 Years of Age
Initiate treatment with 15 mg once daily. If an adequate response is not achieved, consider increasing the dosage to 30 mg once daily. Discontinue RINVOQ if an adequate response is not achieved with the 30 mg dose. Use the lowest effective dose needed to maintain response.

Adults 65 Years of Age and Older

The recommended dosage is 15 mg once daily.

2.6 Recommended Dosage in Patients with Renal Impairment or Severe Hepatic Impairment

Renal Impairment
Atopic Dermatitis:

For patients with severe renal impairment [creatinine clearance (CrCL) < 30 mL/min] the recommended dosage is 15 mg once daily.
No dosage adjustment is needed for patients with mild or moderate renal impairment [(CrCL) > 30 mL/min)].

Hepatic Impairment
RINVOQ is not recommended for use in patients with severe hepatic impairment.

4 CONTRAINDICATIONS

RINVOQ is contraindicated in patients with known hypersensitivity to upadacitinib or any of its excipients.

5 WARNINGS AND PRECAUTIONS

Section 5.6 Hypersensitivity Reactions
Serious hypersensitivity reactions such as anaphylaxis and angioedema were reported in patients receiving RINVOQ in clinical trials. If a clinically significant hypersensitivity reaction occurs, discontinue RINVOQ and institute appropriate therapy.

17 PATIENT COUNSELING INFORMATION

Hypersensitivity Reactions
Advise patients to discontinue RINVOQ and seek immediate medical attention if they develop any signs and symptoms of allergic reactions.

On December 2, 2021, the Prescribing Information and Medication Guide for RINVOQ® (upadacitinib) was updated as a result of discussions with the U.S. Food and Drug Administration (FDA). This follows a Drug Safety Communication (DSC) issued on September 1, 2021, by the FDA based upon its review of a large, randomized, post-marketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing another Janus kinase (JAK) inhibitor to tumor necrosis factor (TNF) blockers.

The indication has been updated to the following:

1 INDICATION AND USAGE
Section 1.1 Rheumatoid Arthritis
RINVOQ (upadacitinib) is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers.

Limitation of Use: Use of RINVOQ in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

The full Prescribing Information now includes new information about the risks of Mortality and Major Adverse Cardiovascular Events and updated information about the risks of Malignancies and Thrombosis within the Boxed Warning and Warnings and Precautions sections.

The Boxed Warning has been updated to the following:

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS

SERIOUS INFECTIONS

Patients treated with RINVOQ are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

If a serious infection develops, interrupt RINVOQ until the infection is controlled.

Reported infections include:

Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before RINVOQ use and during therapy. Treatment for latent infection should be considered prior to RINVOQ use.
Invasive fungal infections, including cryptococcosis and pneumocystosis.
Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.

The risks and benefits of treatment with RINVOQ should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with RINVOQ, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

MORTALITY

In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing another Janus kinase (JAK) inhibitor to tumor necrosis factor (TNF) blockers, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor.

MALIGNANCIES

Lymphoma and other malignancies have been observed in patients treated with RINVOQ. In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer [NMSC]) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk.

MAJOR ADVERSE CARDIOVASCULAR EVENTS

In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue RINVOQ in patients that have experienced a myocardial infarction or stroke.

THROMBOSIS

Thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis have occurred in patients treated with JAK inhibitors used to treat inflammatory conditions. Many of these adverse events were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid RINVOQ in patients at risk. Patients with symptoms of thrombosis should discontinue RINVOQ and be promptly evaluated.

The following sub-sections in the Warnings and Precautions have been updated to the following:

5 WARNINGS AND PRECAUTIONS

Section 5.2 Mortality

In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the JAK inhibitor compared with TNF blockers.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ.

Section 5.3 Malignancy and Lymphoproliferative Disorders
Malignancies were observed in clinical studies of RINVOQ.

In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer [NMSC]) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. In this study, current or past smokers had an additional increased risk of overall malignancies.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy when on treatment, and patients who are current or past smokers.

Non-Melanoma Skin Cancer
NMSCs have been reported in patients treated with RINVOQ. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

Section 5.4 Major Adverse Cardiovascular Events

In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue RINVOQ in patients that have experienced a myocardial infarction or stroke.

Section 5.5 Thrombosis

Thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis, have occurred in patients treated for inflammatory conditions with JAK inhibitors, including RINVOQ. Many of these adverse events were serious and some resulted in death.

In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers.

If symptoms of thrombosis occur, patients should discontinue RINVOQ and be evaluated promptly and treated appropriately. Avoid RINVOQ in patients that may be at increased risk of thrombosis.

This information was added to the following section:

17 PATIENT COUNSELING INFORMATION

Major Adverse Cardiovascular Events

Inform patients that RINVOQ may increase their risk of major adverse cardiovascular events (MACE) including myocardial infarction, stroke, and cardiovascular death. Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events.

The following information on important labeling revisions does not include all changes; please refer to the RINVOQ full Prescribing Information.

Indications and Important Safety Information for RINVOQ (upadacitinib)¹

IMPORTANT SAFETY INFORMATION & INDICATIONS¹

INDICATIONS¹

RINVOQ is indicated for the treatment of:

Moderately to severely active rheumatoid arthritis (RA) in adults who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.
Active psoriatic arthritis (PsA) in adults who have had an inadequate response or intolerance to one or more TNF blockers.
Active ankylosing spondylitis (AS) in adults who have had an inadequate response or intolerance to one or more TNF blockers.
Active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation in adults who have had an inadequate response or intolerance to TNF blocker therapy.

Refractory, moderate to severe atopic dermatitis (AD) in adults and pediatric patients 12 years of age and older whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.

Moderately to severely active ulcerative colitis (UC) in adults who have had an inadequate response or intolerance to one or more TNF blockers.

Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biological therapies for ulcerative colitis, or other potent immunosuppressants such as azathioprine and cyclosporine.

IMPORTANT SAFETY INFORMATION FOR RINVOQ/RINVOQ LQ (upadacitinib)

SERIOUS INFECTIONS

Reported infections include:

Active tuberculosis (TB), which may present with pulmonary or extrapulmonary disease. Test patients for latent TB before RINVOQ use and during therapy. Consider treatment for latent TB infection prior to RINVOQ use.
Invasive fungal infections, including cryptococcosis and pneumocystosis.
Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.

MORTALITY

MALIGNANCIES

Lymphoma and other malignancies have been observed in patients treated with RINVOQ.

MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)

THROMBOSIS

HYPERSENSITIVITY

GASTROINTESTINAL PERFORATIONS

LABORATORY ABNORMALITIES

Neutropenia

Lymphopenia

Anemia

Lipids

Liver enzyme elevations

EMBRYO-FETAL TOXICITY

VACCINATION

MEDICATION RESIDUE IN STOOL

LACTATION

HEPATIC IMPAIRMENT

RINVOQ is not recommended for use in patients with severe hepatic impairment.

ADVERSE REACTIONS

Dosage Forms and Strengths: RINVOQ is available in 15 mg, 30 mg, and 45 mg extended-release tablets. RINVOQ LQ is available in a 1 mg/mL oral solution.

*Unless otherwise stated, “RINVOQ” in the IMPORTANT SAFETY INFORMATION refers to RINVOQ and RINVOQ LQ.

US-RNQ-240118

Please see full Prescribing Information.

Reference: 1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.

US-RNQD-210561

RINVOQ® (upadacitinib) - Healthcare Professional Site (2024)

FAQs

What is the lawsuit against Rinvoq? ›

AbbVie in recent weeks sued Novartis' Sandoz and four other generic drugmakers over copies of its immunology drug Rinvoq (upadacitinib). Though Rinvoq's U.S. patents won't begin to expire until 2033, the suit aims to stop any generic versions from being marketed ahead of those expirations.

Keep Reading ›

What is the new warning for Rinvoq? ›

We are requiring revisions to the Boxed Warning for Xeljanz/Xeljanz XR, Olumiant, and Rinvoq to include information about the risks of serious heart-related events, cancer, blood clots, and death.

Get More Info ›

Why is Rinvoq so expensive? ›

Years of research and testing are needed to ensure that brand-name drugs are safe and effective. This testing can make the drugs expensive. The manufacturer of a brand-name drug can sell the drug for up to 20 years. After that, other drugmakers can market generic versions.

Is Rinvoq hard on your liver? ›

Treatment with RINVOQ was associated with increased incidence of liver enzyme elevation compared to placebo. Evaluate at baseline and thereafter according to routine patient management. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury.

Discover More ›

What is the death rate of Rinvoq? ›

There were eight deaths on RINVOQ (0.6/100PY) and six deaths on adalimumab (1.2/100PY), including non-treatment emergent deaths. There were eight major adverse cardiac events (MACE) through the study duration, including five on RINVOQ (0.4/100PY) and three on adalimumab (0.6/100PY).

Read The Full Story ›

What are the cardiac issues with Rinvoq? ›

Increased risk of major cardiovascular (CV) events, such as heart attack, stroke, or death, in people 50 years and older who have at least 1 heart disease (CV) risk factor, especially if you are a current or past smoker. Blood clots. Blood clots in the veins of the legs or lungs and arteries can happen with RINVOQ.

See Details ›

What to avoid while on Rinvoq? ›

Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine.

Read The Full Story ›

Does Rinvoq cause weight gain? ›

RINVOQ^® may cause weight gain in some people. Weight increase has been reported in RINVOQ^® clinical trials as a common side effect (occurs in 1–10% of patients).

Show Me More ›

How common are blood clots with Rinvoq? ›

Rarely, Rinvoq may cause these types of clots and, in severe cases, death. Symptoms of a blood clot may include pain in a new area of your body, shortness of breath, and swelling or pain. Swelling or pain may affect one or both of your arms, legs, hands, or feet.

Who is a competitor to Rinvoq? ›

Clobetasol topical.
Betamethasone topical.
Protopic.
Dupilumab.
Upadacitinib.
Tacrolimus topical.

Learn More ›

Does Medicare cover Rinvoq in 2024? ›

Do Medicare prescription drug plans cover Rinvoq? Yes. 98% of Medicare prescription drug plans cover this drug.

Get More Info Here ›

What is a substitute for Rinvoq? ›

Remicade.
Sulfasalazine.
Enbrel.
Humira.
Stelara.
Cimzia.