Switch or Cycle - Upadacitinib vs Adalimumab in Refractory RA

Jack Cush, MD

Apr 27, 2026 11:00 am

After the first tumour necrosis factor inhibitor (TNFi) failure, patients with active rheumatoid arthritis (RA) responded by switching to upadacitinib, compared to cycling to a second TNFi, adalimumab.

SELECT-SWITCH trial is an ongoing head-to-head trial that compares upadacitinib to adalimumab for active RA after first TNFi failure at 12 weeks. Patients received either 15 mg once daily upadacitinib or 40 mg every-other-weekly adalimumab. The primary endpoint was achieving superiority in Disease Activity Score 28 (DAS28)–C-reactive protein (CRP) ≤3.2 at week 12.

A total of 492 active RA patients were randomised. At week 12, DAS28-CRP ≤3.2 responses were:

upadacitinib 43.3%
adalimumab 22.4% (difference, 21.0% [95% CI: 12.9-29.1]; P < .0001)

Also superior for UPA were ACR50 (38.2% vs 26.8% [P = .0068]), DAS28-CRP <2.6 (28.4% vs 14.5%; P = .0002), pain reductions (−3.165 vs −2.373; P = .0005), but not in HAQ-DI (−0.523 vs −0.496; P = .5849).

There were no safety differences between treatments.

Patients with rheumatoid arthritis (RA) who achieve timely disease control (ie, clinical remission or low disease activity, per validated metrics) experience improved outcomes, functional status, and quality of life.

Observational data suggest that, after treatment failure with a first tumour necrosis factor inhibitor (TNFi), patients who switch to an advanced therapy with a different mechanism of action (MOA) have better disease activity control and are more likely to persist on therapy compared with those who cycle to a second TNFi; a robust randomised, double-blind clinical trial is needed to confirm these observations.

This trial (and a few others; eg SELECT-COMPARE) suggest that in difficult RA cases, switching therapies (to another MOA) may be more effective than cycling to a different TNFi after first TNFi failure.

Upadacitinib vs adalimumab in patients with rheumatoid arthritis and a prior inadequate response or intolerance to a tumour necrosis factor inhibitor: 12-week results from the randomised, double-blind, SELECT-SWITCH study