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.

Rinvoq is supplied as an extended release capsule for oral administration. The recommended oral dose of Rinvoq is 15 mg once daily with or without food. Rinvoq may be used as monotherapy or in combination with methotrexate or other nonbiologic DMARDs.

Clinical Results

FDA Approval

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

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.

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.