Among methotrexate-naive and methotrexate-inadequate response individuals with active rheumatoid arthritis, upadacitinib monotherapy (at 15 or 30 mg) for 12/14 weeks led to remarkable improvements in pain, health-related quality of life (HRQOL), morning stiffness, work productivity and activity impairment (WPAI), and physical function in comparison with methotrexate alone.

A study was performed to investigate the effect of upadacitinib (a selective Janus kinase 1 inhibitor) monotherapy compared to methotrexate on patient-reported outcomes in moderate-to-severe active rheumatoid arthritis patients who were methotrexate-naive (n=945) or who had an inadequate response to methotrexate (n=648).

The patient-reported outcomes from the SELECT-EARLY and SELECT-MONOTHERAPY trials were assessed at Weeks 2 and 12/14. Included subjects were 18 years of age with rheumatoid arthritis symptoms for six weeks (SELECT-EARLY, methotrexate-naive) or diagnosed rheumatoid arthritis for three months (SELECT-MONOTHERAPY, methotrexate-inadequate response) and received upadacitinib monotherapy (15 or 30 mg) or methotrexate.

The patient-reported outcomes included the following: (i) Patient Global Assessment of Disease Activity (PtGA), (ii) Morning stiffness duration/severity, (iii) Health assessment questionnaire Disability Index (HAQ-DI), (iv) Pain visual analogue scale, (v) HRQOL by the 36-item Short Form Health Survey and WPAI (SELECT-EARLY), and (vi) Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (SELECT-EARLY).

The least square mean alterations and percentage of subjects witnessing improvements higher than or similar to the minimum clinically important differences (MCID) and normative values were assessed. In methotrexate-naive and inadequate response subjects, upadacitinib monotherapy (15 mg, 30 mg) compared to methotrexate led to greater reported  least square mean alteration from baseline at weeks 12/14 in HAQ-DI, PtGA, pain, FACIT-F (SELECT-EARLY), HRQOL, WPAI (SELECT-EARLY), and morning stiffness duration/severity

These alterations were clinically significant with both doses of upadacitinib compared to methotrexate at Weeks 12/14 in both the randomized control trials. Substantial improvements were noted in week 2. In comparison with methotrexate recipients, more upadacitinib-treated methotrexate-naive and inadequate response patients witnessed improvements higher than or comparable to the MCID and scores higher than or similar to the normative values.

Thus, upadacitinib monotherapy improves patient-reported outcomes in rheumatoid arthritis and offers an effective second-line therapy choice for rheumatoid arthritis subjects who have an unsatisfactory response to  methotrexate.