Sustained efficacy of monotherapy with upadacitinib after 48 weeks

In the extension period of the SELECT-MONOTHERAPY trial, clinical and functional outcomes continued to improve in rheumatoid arthritis (RA) patients treated with the Janus kinase (JAK)1 inhibitor upadacitinib [1].

Monotherapy with the oral JAK1-selective inhibitor upadacitinib was assessed over 14 weeks in patients with RA with an inadequate response to methotrexate in the SELECT-MONOTHERAPY trial. In this trial, therapy with upadacitinib showed statistically significant improvements in clinical and functional outcomes versus continuing methotrexate. The safety profile was similar to previous upadacitinib studies, when the JAK1 inhibitor was given together with methotrexate [2].

To further evaluate the efficacy and safety of monotherapy with upadacitinib, a long-term extension period of SELECT-MONOTHERAPY was performed. In the double-blind period, patients on stable methotrexate were randomised to either continue methotrexate or switch to once-daily upadacitinib in 2 doses (15 mg and 30 mg) of monotherapy for 14 weeks. From 14 weeks on, patients previously treated with methotrexate were treated with the lower or higher upadacitinib dose according to a prespecified treatment protocol. Starting at week 26, patients that did not reach clinical disease activity index (CDAI) ≤10 were allowed to use conventional background therapy with disease-modifying drugs in addition to upadacitinib.

During the ACR, the results at 48 weeks were presented [1]. Of 648 patients starting the double-blind phase of the SELECT-MONOTHERAPY trial, 598 (92%) completed 14 weeks and entered the extension period. At 48 weeks, 16% of patients had discontinued treatment. In the extension period, for patients treated with upadacitinib, clinical and functional outcomes continued to improve or were maintained: 55% and 68% of patients treated with upadacitinib 15 mg and 30 mg, respectively, achieved a Disease Activity Score 28/C-reactive protein (DAS28-CRP) <2.6. The corresponding percentages for the CDAI ≤2.8 were 28% and 42%, respectively. Patients that switched from methotrexate to upadacitinib achieved similar responses at week 48 compared to those who received the JAK1 inhibitor from the beginning.

The safety profile was consistent with earlier experiences with upadacitinib. The most frequently reported treatment-emergent adverse events were infections (urinary tract infection, upper respiratory tract infection, nasopharyngitis bronchitis), worsening of RA, herpes zoster, alanine aminotransferase increase, and blood creatine phosphokinase increase. The most frequent serious adverse event was pneumonia (in 8 patients). The higher dose caused more side effects; however, this difference failed to reach statistical significance. Two patients in the upadacitinib 15 mg group developed deep vein thrombosis, and another 2 pulmonary embolisms; all patients affected had at least 1 risk factor for deep vein thrombosis.

The authors concluded that upadacitinib in both doses results in similar improvement in symptoms and physical function in RA patients, with an overall favourable benefit-risk profile.

1. 
   
   1. Smolen J et al. Abstract 0513. ACR 2019, 9-13 November, Atlanta (GA/USA).
   2. Smolen J et al. Lancet 2019;393;2303-2311.

Posted on 4 February 202016 February 2024