Upadacitinib Superior To Abatacept For Arthritis But Sparks More Side Effects

A 24-week phase 3 trial of AbbVie's upadacitinib shows that it produces more remissions and a better score on a rheumatoid arthritis (RA) scale than conventional treatment with abatacept.

But the drug also appeared to be associated with concerning side effects, with one death, a stroke, two venous thromboembolic events and a greater tendency for elevated hepatic aminotransferase levels among the 303 volunteers getting that therapy.

"Longer and larger trials are required in order to determine the effect and safety of upadacitinib in patients with rheumatoid arthritis," the research team led by Dr. Andrea Rubbert-Roth of the Cantonal Hospital in St. Gallen, Switzerland, wrote in the New England Journal of Medicine, where the study appears.

AbbVie paid for the study, known as SELECT-CHOICE.

It is "the first head-to-head trial in RA patients who failed previous biologic DMARD (disease-modifying antirheumatic drug) therapy," Dr. Rubbert-Roth told Reuters Health in an email. "I was surprised that in this difficult-to-treat patient population, not only efficacy of upadacitinib was confirmed but that it was superior to abatacept. That presents a valid treatment option" for patients with moderate to severe RA.

Upadacitinib is an oral selective Janus kinase inhibitor approved in August 2019 by the U.S. Food and Drug Administration. Sold under the brand name Rinvoq, it costs about $59,000 a year. Abatacept, sold by Bristol Myers Squibb under the brand name Orencia, is a T-cell costimulation modulator, selling for $42,000 per year, according to goodrx.com.

In the new double-blind test, eligible patients needed to have either six or more swollen joints, or six or more tender joints in addition to a high-sensitivity C-reactive protein level of 3 mg per liter or higher, despite 3 months of therapy with at least one DMARD.

The volunteers continued to take conventional synthetic DMARDs, nonsteroidal antiinflammatory drugs, acetaminophen, or oral or inhaled glucocorticoids.

The team used a Disease Activity Score for 28 joints where the rate of remission ranges from 0 to 9.4 (with 9.4 indicating the most severe disease). It's calculated based on joint status and C-reactive protein levels.

The research team found that the score with upadacitinib dropped 2.52 points from 5.70 points after 12 weeks. In the abatacept group the baseline score was 5.88 and dropped just 2.00 points (P<0.001).

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"A decrease of 1.2 (is) considered to be a significant change for an individual patient," the researchers said.

In all, 30.0% of upadacitinib recipients had a remission compared with 13.3% with abatacept (P<0.001).

Abatacept may be one of the weaker drugs in its class. A 2019 study in the BMJ suggested that rituximab and tocilizumab were better on a number of measures.

Serious adverse events surfaced in 3.3% of upadacitinib recipients versus 1.6% taking abatacept. The rates of serious infections were 1.0% and 0.3% respectively.

Dr. Rubbert-Roth, deputy director of the division of rheumatology at Cantonal, said she was "surprised that herpes zoster was observed in both treatment arms as there is the assumption that this is more frequently being observed with JAK inhibitors."

The rates of hepatic disorders were 7.6% with upadacitinib and 1.6% with abatacept; most cases were classified by the authors as "nonserious."

"The side effect profile of upadacitinib seen in the SELECT-CHOICE study is consistent with that seen in the five phase 3 clinical trials that were submitted to the regulatory authorities in the USA and Europe," said Dr. Rubbert-Roth.

The drug already carries a warning label that cites risks of serious infections, lymphoma, and the potential for blood clots seen in recipients of JAK inhibitors.

"The long-term extension phase of the SELECT-CHOICE study is currently ongoing and all patients who continue on this extension phase will receive upadacitinib open-label for at least 4 years," the researcher said.

—Gene Emery

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