Rinvoq (upadacitinib) - 7 indications

Scroll down for more information on each indication:

• for the treatment of adults with rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate; approved August 2019
• for adults with active psoriatic arthritis who have had an inadequate response or intolerance to one or more TNF blockers; approved December of 2021
• for the treatment of moderate to severe atopic dermatitis in adults and children 12 years of age and older whose disease did not respond to previous treatment and is not well controlled with other treatments; approved January of 2022
• for the treatment of adults with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers; approved March of 2022
• for the treatment of adults with active ankylosing spondylitis who have had an inadequate response or intolerance to one or more TNF blockers; approved April of 2022
• for the treatment of adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation who have had an inadequate response or intolerance to TNF blocker therapy; approved October of 2022
• for the treatment of adults with moderately to severely active Crohn's disease; approved May of 2023

General Information

Rinvoq (upadacitinib) is a Janus kinase (JAK) inhibitor.

Rinvoq is specifically indicated for:

• the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate
• the treatment of adults with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers
• for the treatment of moderate to severe atopic dermatitis in adults and children 12 years of age and older whose disease did not respond to previous treatment and is not well controlled with other pills or injections, including biologic medicines, or when use of other pills or injections is not recommended
• for the treatment of adults with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers
• for the treatment of adults with active ankylosing spondylitis who have had an inadequate response or intolerance to one or more TNF blockers
• for the treatment of adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation who have had an inadequate response or intolerance to TNF blocker therapy.
• for the treatment of adults with moderately to severely active Crohn’s disease who have had an inadequate response or intolerance to one or more TNF blockers.

Rinvoq is supplied as an extended release capsule for oral administration. Scroll down for recommended dosing for each indication.

Mechanism of Action

Rinvoq (upadacitinib) is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs) which modulate intracellular activity including gene expression. Upadacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs. 

Side Effects

Adverse effects associated with the use of Rinvoq may include, but are not limited to, the following:

•  upper respiratory tract infections
• nausea
• cough
• pyrexia

The Rinvoq drug label comes with the following Black Box Warning: • Serious infections leading to hospitalization or death, including tuberculosis and bacterial, invasive fungal, viral, and other opportunistic infections, have occurred in patients receiving Rinvoq. • If a serious infection develops, interrupt Rinvoq until the infection is controlled. • Prior to starting Rinvoq, perform a test for latent tuberculosis; if it is positive, start treatment for tuberculosis prior to starting Rinvoq.  • Monitor all patients for active tuberculosis during treatment, even if the initial latent tuberculosis test is negative. • Lymphoma and other malignancies have been observed in patients treated with Rinvoq. • Thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated with Janus kinase inhibitors used to treat inflammatory conditions.

Indication 1 - for the treatment of adults with rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate

approved August 2019

Dosing/Administration

The recommended dose is 15 mg once daily.

Clinical Trial Results

The FDA approval of Rinvoq was based on data from the SELECT program, one of the largest registrational Phase 3 programs in RA with approximately 4,400 patients evaluated across all treatment arms in five studies. The studies include assessments of efficacy, safety and tolerability across a variety of RA patients, including those who failed or were intolerant to biologic disease-modifying anti-rheumatic drugs and who were naïve or inadequate responders to methotrexate. Across the SELECT Phase 3 studies, Rinvoq met all primary and ranked secondary endpoints. The primary endpoints include:

• In SELECT-EARLY, 52 percent of MTX-naïve patients treated with Rinvoq 15 mg achieved ACR50 vs 28 percent treated with MTX at week 12
• In SELECT-MONOTHERAPY, 68 percent of MTX-IR patients treated with Rinvoq 15 mg achieved ACR20 vs 41 percent treated with continued MTX at week 14
• In SELECT-COMPARE, 71 percent of MTX-IR patients treated with Rinvoq 15 mg plus MTX achieved ACR20 vs 36 percent treated with placebo plus MTX at week 12
• In SELECT-NEXT, 64 percent of csDMARD-IR patients treated with Rinvoq 15 mg plus csDMARDs achieved ACR20 vs 36 percent treated with placebo plus csDMARDs at week 12
• In SELECT-BEYOND, 65 percent of biologic-IR patients treated with Rinvoq 15 mg plus csDMARDs achieved ACR20 vs 28 percent treated with placebo plus csDMARDs at week 12

Indication 2 - for adults with active psoriatic arthritis who have had an inadequate response or intolerance to one or more TNF blockers

approved December of 2021

Dosing/Administration

The recommended dose is 15 mg once daily

Clinical Trial Results

The FDA approval is supported by data from two pivotal Phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2, Across the SELECT-PsA 1 and SELECT-PsA 2 trials, Rinvoq met its primary endpoint of ACR20 at week 12 with patients taking Rinvoq 15 mg achieving significantly higher ACR20 responses (71% and 57%, respectively) versus placebo (36% and 24%, respectively).

Indication 3 - for the treatment of moderate to severe atopic dermatitis in adults and children 12 years of age and older

approved January of 2022

Dosing/Administration

Rinvoq 15 mg once daily can be initiated in adults and children 12 years of age and older weighing at least 40 kg. In these children and adults less than 65 years of age who do not achieve an adequate response, the dose may be increased to 30 mg once daily.

Clinical Trial Results

Approval was based on more than 2,500 patients evaluated across three studies. Approximately 52 percent of the patients had prior exposure to systemic atopic dermatitis treatment. These studies evaluated the efficacy and safety of Rinvoq monotherapy (Measure Up 1 and 2) and with topical corticosteroids (AD Up), compared to placebo, in adults and children 12 years of age and older with moderate to severe atopic dermatitis. Across the three atopic dermatitis pivotal studies, Rinvoq (15 mg and 30 mg, once daily) monotherapy and with topical corticosteroids met all primary and secondary endpoints at week 16, with some patients achieving higher levels of skin clearance (EASI 90 and 100).

Indication 4 - adults with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to one or more TNF blockers

Approved March of 2022

Dosing/Administration

• Induction: The recommended induction dose of Rinvoq is 45 mg once daily for 8 weeks.
• Maintenance: The recommended dose of Rinvoq for maintenance treatment is 15 mg once daily. A dosage of 30 mg once daily may be considered for patients with refractory, severe or extensive disease. Discontinue Rinvoq if an adequate therapeutic response is not achieved with the 30 mg dosage. Use the lowest effective dosage needed to maintain response.

Clinical Trial Results

The FDA approval was based on three Phase 3 randomized, double-blind, placebo-controlled clinical studies: two induction studies (U-ACHIEVE Induction and U-ACCOMPLISH) and one maintenance study, U-ACHIEVE maintenance. The trials evaluated upadacitinib 45 mg once daily as induction therapy, and upadacitinib 15 mg and 30 mg once daily as maintenance therapy. The primary endpoints were clinical remission per modified Mayo Score (mMS) at week 8 for the induction clinical trials and at week 52 for the maintenance trial. 

During the U-ACHIEVE and U-ACCOMPLISH induction trials at week 8, 26% and 33% of patients treated with Rinvoq 45 mg achieved clinical remission, compared to 5% and 4% of patients who received placebo. During the maintenance trial, 42% and 52% of patients treated with Rinvoq 15 mg or 30 mg, respectively, achieved clinical remission at week 52 compared to 12% of patients who received placebo. In addition, the studies met all ranked secondary endpoints, including endoscopic improvement and histologic-endoscopic mucosal improvement (HEMI), as well as corticosteroid-free clinical remission in the maintenance study.

Indication 5 - for the treatment of adults with active ankylosing spondylitis who have had an inadequate response or intolerance to one or more TNF blockers

approved April of 2022

Dosing/Administration

The recommended dosage is 15 mg once daily

Clinical Trial Results

FDA approval was based on the Phase 3 SELECT-AXIS 2 clinical trial (Study 1) evaluating Rinvoq in patients who had an inadequate response or intolerance to one or two biologic disease-modifying anti-rheumatic drugs (bDMARDs) and the Phase 2/3 SELECT-AXIS 1 clinical trial evaluating Rinvoq in patients who were naïve to bDMARDs and had an inadequate response or intolerance to at least two nonsteroidal anti-inflammatory drugs (NSAIDs).

The primary endpoint of both trials was ASAS40, a composite index that measures disease activity. To achieve an ASAS40 response, a patient's disease activity must have improved by at least 40%, as well as improved by two units in at least three of four disease areas assessed, and the remaining area must not have gotten worse, including back pain, patient global assessment of disease activity, physical functional and morning stiffness.

In both SELECT-AXIS 1 and SELECT-AXIS 2 clinical trials, a significantly greater proportion of patients receiving oral Rinvoq 15 mg achieved an ASAS40 response (51% and 44.5%, respectively) compared to those receiving placebo (26% and 18.2%, respectively) at week 14. Clinical responses were observed as early as week four in SELECT-AXIS 2 for ASAS40.

Indication 6 - for the treatment of adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation who have had an inadequate response or intolerance to TNF blocker therapy

Approved October of 2022 

Dosing/Administration

The recommended dosage is 15 mg once daily.

Clinical Trial Results

FDA approval was based on data from the Phase 3 SELECT-AXIS 2 clinical trial, which assessed the efficacy, safety, and tolerability of Rinvoq in adults with active nr-axSpA. Among patients who received Rinvoq 15 mg, nearly half achieved an ASAS40 response, the primary endpoint, at week 14 compared to placebo (44.9 percent vs. 22.3 percent respectively). ASAS40 responses were observed as early as two weeks in nr-axSpA patients treated with Rinvoq.

Indication 7 -  the treatment of adults with moderately to severely active Crohn’s disease who have had an inadequate response or intolerance to one or more TNF blockers

Approved May of 2023

Dosing/Administration

The recommended induction dosage is 45 mg once daily for 12 weeks. The recommended maintenance dosage is 15 mg once daily. A maintenance dosage of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease. Discontinue Rinvoq if an adequate therapeutic response is not achieved with the 30 mg dosage. Use the lowest effective dosage needed to maintain response.

Clinical Trial Results

The FDA approval of Rinvoq for Crohn's disease was based on two induction studies, U-EXCEED and U-EXCEL, and the U-ENDURE maintenance study. Statistical significance was achieved for the co-primary endpoints and key secondary endpoints with Rinvoq 45 mg in the induction studies and Rinvoq 15 mg and 30 mg in the maintenance study compared to placebo.

• Endoscopic response: In the two induction studies, 34% and 46% of patients treated with Rinvoq 45 mg achieved endoscopic response (defined as a decrease of greater than 50% from the baseline Simplified Endoscopic Score for CD [SES-CD] or for patients with isolated ileal disease and a baseline SES-CD of 4, at least a 2-point reduction from baseline) at week 12, respectively, compared to 3% and 13% of patients receiving placebo. In the maintenance study, 28% and 41% of patients treated with Rinvoq 15 mg and 30 mg achieved endoscopic response at week 52, respectively, compared to 7% of patients receiving placebo.
• Clinical remission: In the two induction studies, 36% and 46% of patients treated with Rinvoq 45 mg achieved clinical remission (defined as a Crohn's Disease Activity Index [CDAI] of less than 150) at 12 weeks, respectively, compared to 18% and 23% of patients receiving placebo. Additionally, in the maintenance trial, 42% and 55% of patients treated with Rinvoq 15 mg and 30 mg achieved clinical remission at 52 weeks, respectively, compared to 14% of patients receiving placebo.

The onset of clinical response based on CDAI was observed as early as two weeks in U-EXCEED and U-EXCEL, with a greater proportion of patients achieving clinical response at week 2 in Rinvoq-treated patients compared with placebo.