INDICATION¹

RINVOQ 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.

Important Safety Information¹

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

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 major adverse cardiovascular events (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

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 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 gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs). 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 varicella zoster or prophylactic herpes zoster vaccinations, in agreement with current immunization guidelines.

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, and rash.

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.

Please see full Prescribing Information.

ACR=American College of Rheumatology;

ACR20=improvement of at least 20% in tender 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; IR=intolerance or inadequate response; MTX=methotrexate; TNFi=tumor necrosis factor inhibitor

ReFERENCES

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

2. Data on file. ABVRRTI68885.

3. 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.

4. 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.

5. Smolen J, Emery P, Rigby W, et al. Upadacitinib as monotherapy in patients with rheumatoid arthritis and prior inadequate response to methotrexate: results at 84 weeks from the SELECT-MONOTHERAPY study. The American College of Rheumatology, 5-9 November 2020, E-Congress.

6. Genovese MC, Combe B, Hall S et al. Upadacitinib in patients with rheumatoid arthritis and an inadequate response or intolerance to biological DMARDs: results at 60 weeks from the SELECT-BEYOND study. Poster presented at: The European Congress of Rheumatology, 12-15 June 2019.

7. Data on File. ABVRRTI72945.

©2022 AbbVie. All rights reserved. RINVOQ^® and its design are registered trademarks of AbbVie Biotechnology Ltd.

US-RNQR-220738 October 2022