Rheumatoid arthritis

JAK inhibitor wins in head to head with abatacept

Upadactinib has been shown to have a superior efficacy to abatacept in patients with rheumatoid arthritis refractory to previous biologic therapy.

The international SELECT-CHOICE trial randomised 612 patients from 120 sites across 28 countries including Australia to either the oral JAK1 inhibitor or IV abatacept

Patients in the upadacitinib group also received IV placebo and patients in the abatacept group also received oral placebo. All patients were allowed to continue on background conventional synthetic DMARDs, NSAIDs, acetaminophen, or oral/inhaled glucocorticoids.

The study, published in the NEJM, found the mean change from baseline in the DAS28-CRP at week 12, was −2.52 points in the upadacitinib group and −2.00 points in the abatacept group ( p<0.001).

The remission rate according to a DAS28-CRP of less than 2.6 was 30.0% with upadacitinib and 13.3% with abatacept (p<0.001).

“The finding that remission according to the DAS28-CRP occurred in 30.0% of the patients in the upadacitinib group is consistent with the findings of other phase 3 trials of upadacitinib involving patients with rheumatoid arthritis who had not previously received methotrexate or who had had an inadequate response to methotrexate, conventional synthetic DMARDs, or biologic DMARDs,” the study said.

The study also found serious adverse events (3.3.% v 1.6%) and serious infections (1% v 0.3%) were more common with upadacitinib than with abatacept.

“Two adjudicated venous thromboembolic events, one major adverse cardiac event, and a higher percentage of patients with grade 3 or 4 elevations in hepatic enzyme and creatine kinase levels were reported with upadacitinib,” the study said.

“In patients with rheumatoid arthritis refractory to previous biologic DMARD therapy, upadacitinib was superior to abatacept with regard to remission but was associated with more adverse events and serious adverse events,” it concluded.

Co-investigator on the study, Associate Professor Maureen Rischmueller told the limbic that the robust remission rate of 30%, no new red flags for safety, and the patient convenience of a once daily tablet made upadacitinib a useful option.

“A lot of my colleagues and I are using upadacitinib as a first line agent after the failure of conventional DMARDS in people with rheumatoid arthritis.”

“It’s another option available for consideration and like other biologics and targeted synthetic agents, patients need to be carefully selected with respect to their medical history.”

Associate Professor Rischmueller, from the Queen Elizabeth Hospital and University of Adelaide, said some of her patients have called the treatment ‘life-changing’.

Participants in the SELECT-CHOICE study have been invited into an open label extension study to provide long term data on upadacitinib.

She added the JAK inhibitor was also showing benefit in psoriatic arthritis studies underway.

An Editorial in the NEJM said the study helps position JAK inhibitors at the forefront when patients had an inadequate response to a biologic DMARD.

“In order to compete in the crowded field of targeted treatments for rheumatoid arthritis, JAK inhibitors not only have to prove that they are efficacious and safe — they also need to be less expensive than or clinically superior to biologic DMARDs.”

“Rheumatologists will be looking hard at future data to assess whether improved treatment outcomes justify an increased risk of adverse events.”

Upadacitinib was listed on the PBS for rheumatoid arthritis in May 2020.

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