Inhibition of Structural Joint Damage Progression with Upadacitinib in Rheumatoid Arthritis: 1-Year Outcomes from the SELECT Phase 3 Program.

To evaluate the inhibition of progression of structural joint damage through week 48 in patients with moderately to severely active rheumatoid arthritis (RA) receiving upadacitinib as monotherapy or in combination with methotrexate. Radiographic progression was assessed in two phase 3 randomized-controlled trials. Methotrexate-naïve patients were randomized to upadacitinib 15 or 30 mg once daily (QD) or methotrexate monotherapy (SELECT-EARLY, n = 945), while methotrexate inadequate responders (IR) were randomized to upadacitinib 15 mg QD or adalimumab 40 mg every other week or placebo added to background methotrexate (SELECT-COMPARE, n = 1629). Mean changes from baseline in modified Total Sharp Score (mTSS), joint space narrowing (JSN), and erosion scores (ES) were determined. Data were analysed both by linear extrapolation for missing data imputation and treatment switching and as-observed. In patients naïve or with limited exposure to methotrexate (SELECT-EARLY), mean changes from baseline to week 48 in mTSS were 0.03 for upadacitinib 15 mg, 0.14 for upadacitinib 30 mg, and 1.00 for methotrexate based on linear extrapolation (p < 0.001 for both upadacitinib doses vs methotrexate). Among patients with an inadequate response to methotrexate (SELECT-COMPARE), the mean change from baseline in mTSS was significantly reduced in the upadacitinib 15 mg plus methotrexate group vs placebo plus methotrexate (0.28 vs 1.73; p < 0.001); mean change from baseline in the adalimumab plus methotrexate group was 0.39. Upadacitinib monotherapy or in combination with background methotrexate was effective in inhibiting the progression of structural joint damage through week 48 in methotrexate-naïve and methotrexate-IR patients with RA. ClinicalTrials.gov, https://clinicaltrials.gov, NCT02706873 and NCT02629159