The FDA ( U.S. Food and Drug Administration ) has approved Rinvoq ( Upadacitinib ), a 15 mg, once-daily oral Janus kinase ( JAK ) inhibitor, for the treatment of adults with moderately to severely active rheumatoid arthritis ( RA ) who have had an inadequate response or intolerance to Methotrexate ( MTX-IR ).
The FDA approval of Rinvoq is supported by data from the SELECT program, one of the largest registrational phase 3 programs in rheumatoid arthritis with approximately 4,400 patients evaluated across all treatment arms in five studies.
The studies have included assessments of efficacy, safety and tolerability across a variety of rheumatoid arthritis patients, including those who failed or were intolerant to biologic disease-modifying anti-rheumatic drugs and who were naïve or inadequate responders to Methotrexate. Rinvoq is not indicated for Methotrexate-naïve patients.
Across the SELECT phase 3 studies, Rinvoq met all primary and ranked secondary endpoints. The primary endpoints include:
A) in SELECT-EARLY, 52% of Methotrexate-naïve patients treated with Upadacitinib 15 mg achieved ACR50 versus 28% treated with Methotrexate at week 121;
B) in SELECT-MONOTHERAPY, 68% of MTX-IR patients treated with Upadacitinib 15 mg achieved ACR20 vs 41% treated with continued Methotrexate at week 141;
C) in SELECT-COMPARE, 71% of MTX-IR patients treated with Upadacitinib 15 mg plus Methotrexate achieved ACR20 vs 36% treated with placebo plus Methotrexate at week 121;
D) in SELECT-NEXT, 64% of csDMARD-IR patients treated with Upadacitinib 15 mg plus csDMARDs achieved ACR20 vs 36% treated with placebo plus csDMARDs ( conventional synthetic DMARDs ) at week 121;
E) in SELECT-BEYOND, 65% of biologic-IR patients treated with Upadacitinib 15 mg plus csDMARDs achieved ACR20 vs 28% treated with placebo plus csDMARDs at week 121.
Patients taking Upadacitinib have achieved clinical remission, a state characterized by almost no disease activity and symptoms, even without Methotrexate.
Approximately 30% of patients treated with Upadacitinib has achieved clinical remission ( as assessed by DAS28-CRP less than 2.6 ) at week 12 in SELECT-COMPARE and week 14 in SELECT-MONOTHERAPY compared to 6% with placebo plus Methotrexate and 8% with Methotrexate, respectively.
In SELECT-EARLY, 36% of patients treated with Upadacitinib has achieved clinical remission ( as assessed by DAS28-CRP less than 2.6 ) at week 12 compared to 14% with Methotrexate.
Durable remission rates were observed up to week 26. Forty-eight percent of patients treated with Upadacitinib alone in SELECT-EARLY and 41% of patients treated with Upadacitinib plus Methotrexate in SELECT-COMPARE have achieved clinical remission at weeks 24 and 26, compared to 9% with placebo plus Methotrexate and 18% with Methotrexate, respectively.
Analysis at weeks 24 and 26 were not controlled for multiple comparisons.
Upadacitinib has significantly inhibited radiographic progression as measured by the change in modified total Sharp score ( mTSS ) from baseline compared to Methotrexate in SELECT-EARLY ( 0.14 vs 0.67 ), and Upadacitinib plus Methotrexate compared to placebo plus Methotrexate in SELECT-COMPARE (0.15 vs 0.78) through weeks 24 and 26, respectively.
The most common side effects associated with Upadacitinib include upper respiratory tract infections ( common cold, sinus infections ), nausea, cough and pyrexia.
Patients treated with Upadacitinib are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include tuberculosis, invasive fungal, bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as Methotrexate or corticosteroids.
Lymphoma and other malignancies have been observed in Upadacitinib-treated patients.
Thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated with JAK inhibitors used to treat inflammatory conditions.
Patients treated with Upadacitinib also may be at risk for other serious adverse reactions, including gastrointestinal perforations, neutropenia, lymphopenia, anemia, lipid elevations, liver enzyme elevations, and embryo-fetal toxicity. ( Xagena )
Source: Abbvie, 2019