Trial suggests JAK1 inhibitor is superior to methotrexate for treatment of early rheumatoid arthritis

Upadacitinib, a selective Janus kinase inhibitor, is currently only indicated for specialist treatment of rheumatoid arthritis.

Rheumatoid arthritis

A selective Janus kinase (JAK1) inhibitor, upadacitinib, is superior to methotrexate in improving clinical outcomes in patients with early rheumatoid arthritis (RA), a study in Arthritis and Rheumatology has suggested

Methotrexate is currently recommended as a first-line treatment for patients with newly-diagnosed active RA. Upadacitinib is only indicated for specialist treatment of RA. 

In the double-blind, phase III study — sponsored by AbbVie, which manufactures upadacitinib under the brand name Rinvoq — 947 patients with RA were randomised to receive 15mg or 30mg of upadacitinib monotherapy once-daily, or 7.5–20mg of methotrexate weekly. Patients were either naïve to methotrexate or had received methotrexate for three or fewer weekly doses and completed a four-week washout before the first dose of study drug.

The researchers found that both doses of upadacitinib were superior to methotrexate in all efficacy outcomes.

At week 12, the proportion of patients who had achieved the primary endpoint of ≥50% response according to the American College of Rheumatology criteria was 52% and 56% in the 15mg and 30mg upadacitinib groups respectively, compared with 28% in the methotrexate group (P<0.001).

Overall, 88% and 89% of upadacitinib 15mg and 30mg patients, respectively, had no radiographic progression compared with 78% in the methotrexate group.

Up to week 24, the frequency of adverse events was similar in the upadacitinib 15mg arm and the methotrexate group, but slightly higher in the upadacitinib 30mg arm. In total, six deaths occurred, three of which were in the upadacitinib 30mg group.

The authors concluded that both doses of upadacitinib monotherapy demonstrated significant improvements in clinical, radiographic and patient-reported outcomes versus methotrexate.

“This trial convincingly demonstrates the efficacy of the JAK1 inhibitor upadacitinib as monotherapy in early rheumatoid arthritis. It works faster and better than methotrexate alone,” said Ronald van Vollenhoven, professor of rheumatology at the Amsterdam University Medical Center in the Netherlands and lead author of the study.

“The latter drug can be combined with corticosteroids to obtain a more rapid effect, and future studies will perhaps use that comparison.”

Peter Taylor, chief medical advisor at the National Rheumatoid Arthritis Society, said the findings were “of importance” because a proportion of RA patients are intolerant to methotrexate. 

“Tofacitinib, baricitinib, upadacitinib and filgotinib have all shown numerically and statistically significantly better outcomes for various endpoints in early methotrexate-naïve RA versus methotrexate,” he said. “Whether or not superiority can be claimed depends on the multiplicity adjustments and pre-study defined hierarchical analysis in individual clinical trial designs. 

“The findings are of importance because a proportion of patients are intolerant of methotrexate to varying degrees. But the EULAR [European League Against Rheumatism] recommendations rightly propose that where JAK inhibitors are used, they should be added to methotrexate where reasonably possible.”

Taylor added that, in the case that a monotherapy is required because of methotrexate intolerance or contraindication, then either a JAK inhibitor, such as upadacitinib, or a biologic IL-6 receptor inhibitor would be needed.



Last updated
The Pharmaceutical Journal, Trial suggests JAK1 inhibitor is superior to methotrexate for treatment of early rheumatoid arthritis;Online:DOI:10.1211/PJ.2020.20208165

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