Is upadacitinib more effective than adalimumab in patients with rheumatoid arthritis treated with methotrexate?

This study investigated upadacitinib (Rinvoq) versus adalimumab (Humira) as add-on to methotrexate in patients with rheumatoid arthritis (RA).

They found that upadacitinib was more effective in improving RA symptoms compared to adalimumab.

Rheumatoid arthritis (RA) is an auto-immune condition. It leads to painful swelling and tissue loss in the joints. Disease-modifying anti-rheumatic drugs (DMARDs) can treat RA. Methotrexate (MTX) is a DMARD. It is usually the first line treatment for RA. Overtime patients may become unresponsive to some DMARDs, including MTX. The next treatment option is a biological DMARD (bDMARD). bDMARDs target specific inflammatory proteins. Adalimumab (ADL) is a bDMARD. It targets tumor necrosis factor (TNF).

Some patients may still be unresponsive after the addition of a bDMARD. Drugs that target the Janus kinase (JAK) pathway are a promising option for these patients. Upadacitinib (UPD) is a JAK1 enzyme inhibitor. It is unclear if UPD improves RA symptoms compared to ADL in combination with MTX.

This study included 1629 patients with RA. Patients were randomly assigned to UPD, ADL or placebo (inactive drug, until week 26 only). Patients also continued with MTX. At 26 weeks, patients that did not respond to ADL were allowed to switch to UPD, and vice versa. Patients in the placebo group were also switched to UPD at 26 weeks. Patients were treated for up to 48 weeks. The ACR20/50/70 criteria was used to measure RA symptoms. For example, ACR20 was a 20% improvement in symptoms.  X-rays were also performed to assess joint damage. 

At 48 weeks, more UPD-treated patients reached the ACR target (65% for ACR20, 49% for ACR50 and 36% for ACR70). This compared to 54%, 40% and 23% of ADL-treated patients. A 62% improvement in disability score was observed with UPD compared to 52% with ADL. UPD was also better than ADL in reducing pain and morning stiffness.

Low disease activity (LDA) and remission rates were also higher in UPD-treated patients (LDA: 47% vs. 34%; remission: 25% vs. 17%). The rate of side effects was higher for ADL. Most common side effects with UPD included respiratory and urinary infections. Most common side effects with ADL included urinary infection and worsening RA.

The authors concluded that UPD improved RA symptoms compared to ADL as add-ons to MTX.

This study was funded by AbbVie, the manufacturer of upadacitinib and adalimumab.