FDA Approves Upadacitinib for Severely Active RA

The FDA has approved Upadacitinib (Rinvoq, AbbVie) for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate. 

Upadacitinib is a Janus kinase (JAK) inhibitor not recommended to be used in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine. 

"Despite the availability of multiple treatment options with varying mechanisms of action, many patients still do not achieve clinical remission or low disease activity-the primary treatment goals for rheumatoid arthritis," said Roy M. Fleischmann, MD, primary investigator for SELECT-COMPARE and clinical professor at the University of Texas Southwestern Medical Center at Dallas in a statement. "With this FDA approval, Rinvoq has the potential to help additional people living with RA achieve remission who have not yet reached this goal."

Prescribing information for upadacitinib includes warnings of serious infections, malignancy, thrombosis, gastrointestinal perforations, and embryo-fetal toxicity that may arise from the use of the treatment. Laboratory monitoring is recommended due to potential changes in lymphocytes, neutrophils, hemoglobin, liver enzymes and lipids. Upadacitinib should not be used with live vaccines. 

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Upadacitinib’s approval stems from the results of a large SELECT study that included 4,400 patients across a variety of study arms. Patients included those who failed or were intolerant to biologic disease-modifying anti-rheumatic drugs and who were naïve or inadequate responders to methotrexate.

Clinical Remissions

30% of patients treated with upadacitinib achieved clinical remission (ie almost no disease activity and symptoms), even without methotrexate at week 12 in the SELECT-COMPARE arm and week 14 in the SELECT-MONOTHERAPY arm. These results are compared with the 6% of patients that achieved clinical remission in the placebo plus methotrexate arm, and 8% that received methotrexate arm, respectively.

In the SELECT-EARLY arm, 48% of patients treated with upadacitinib alone achieved clinical remission by week 24, compared with 9% of patients treated with placebo plus methotrexate. 

In the SELECT-COMPARE arm, 41% of patients achieved clinical remission by week 26, compared with only 18% in the methotrexate only group. 

Durable remission rates were observed up to week 26. 

Radiographic Inhibition

Study results were also reported to show a significant inhibition in radiographic progression, according to AbbVie’s release. 

Adverse Events

The most common adverse events reported with the use of upadacitinib include upper respiratory tract infections, nausea, cough, and pyrexia. 

Prescribing information for upadacitinib includes a boxed warning for serious infections included tuberculosis and bacterial, invasive fungal, oral, and other opportunistic infections that have led to hospitalizations in some patients. 

Full Prescribing Information