Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response

Abstract

BackgroundIn SELECT-COMPARE, a randomised double-blind study, upadacitinib 15 mg once daily was superior to placebo or adalimumab on background methotrexate (MTX) for treating rheumatoid arthritis signs and symptoms and inhibited radiographical progression versus placebo at 26 weeks. Here we report 48-week safety and efficacy in patients who continued their original medication or were rescued to the alternative medication for insufficient response.MethodsPatients on MTX received upadacitinib 15 mg, placebo or adalimumab for 48 weeks. Rescue without washout, from placebo or adalimumab to upadacitinib or upadacitinib to adalimumab occurred if patients had <20% improvement in tender joint count (TJC) or swollen joint count (SJC) (weeks 14/18/22) or Clinical Disease Activity Index (CDAI) >10 (week 26); remaining placebo patients were switched to upadacitinib at week 26. Efficacy was analysed by randomised group (non-responder imputation), as well as separately for rescued patients (as observed). Treatment-emergent adverse events per 100 patient-years were summarised.ResultsConsistent with responses through week 26, from weeks 26 to 48, responses by randomised group including low disease activity, clinical remission and improvements in pain and function remained superior for upadacitinib versus adalimumab; radiographical progression remained lower for upadacitinib versus placebo (linear extrapolation). Although both switch groups responded, a higher proportion of patients rescued to upadacitinib from adalimumab achieved CDAI ≤10 at 6 months postswitch versus patients rescued from upadacitinib to adalimumab. Safety at week 48 was comparable to week 26.ConclusionUpadacitinib+MTX demonstrated superior clinical and functional responses versus adalimumab+MTX and maintained inhibition of structural damage versus placebo+MTX through week 48. Patients with an insufficient response to adalimumab or upadacitinib safely achieved clinically meaningful responses after switching to the alternative medication without washout.

Upadacitinib versus placebo or adalimumab with background methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate: a subgroup analysis of a phase III randomized controlled trial in Central and Eastern European patients

“…The safety profile of upadacitinib over 48 weeks was similar to that of adalimumab except for higher rates of herpes zoster (HZ) and creatine phosphokinase elevations. 7 , 11 The increased rates of HZ observed with upadacitinib are consistent with previous reports of HZ across approved JAK inhibitors, including tofacitinib and baricitinib. 12 – 14 …”

“…SELECT-COMPARE is an ongoing phase III, randomized, placebo- and active-controlled, double-blind trial that has evaluated the safety and efficacy of upadacitinib 15 mg once daily (QD) versus placebo or adalimumab 40 mg every other week, each in combination with stable background MTX, in patients with MTX-IR RA. 7 , 11 Upadacitinib 15 mg QD achieved both primary endpoints, ≥20% improvement in ACR response criteria (ACR20) and Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) <2.6 at week 12 versus placebo, and was superior versus adalimumab in ranked, multiplicity-adjusted endpoints of ≥50% improvement in ACR response criteria (ACR50) and change from baseline in pain and Health Assessment Questionnaire-Disability Index (HAQ-DI) at week 12. In addition, upadacitinib 15 mg QD achieved significantly greater inhibition in van der Heijde’s modification of the Total Sharp Score (mTSS) versus placebo at week 26.…”

Efficacy of JAK inhibitors in Crohn’s Disease

“…Fedratinib (SAR302503; trade name Inrebic) was approved the FDA in August 2019 for treatment of myelofibrosis and essential thrombocythemia 33 . Upadacitinib (trade name Rinvoq; ABT-494) targeting mainly JAK1 also was approved by the FDA for the treatment of rheumatoid arthritis in August 2019 [34][35][36][37][38] .…”

Upadacitinib for the treatment of rheumatoid arthritis

“…In patients for whom methotrexate alone was inadequate, adding upadacitinib, adalimumab or placebo achieved remission in 29%, 18% and 6% respectively after 12 weeks . Over 48 weeks of treatment, upadacitinib was associated with superior clinical responses, including low disease activity and remission, compared with adalimumab (see Figure ) …”