Switch Between JAK And TNF Inhibitors Safe, Effective For Rheumatoid Arthritis

Rheumatoid arthritis patients who experience little or no reduction in symptoms from either Janus kinase (JAK) or tumor necrosis factor (TNF) inhibitor may achieve treatment goals by switching from one medicine to the other, a recent study suggests.

Researchers randomized rheumatoid arthritis patients to receive adalimumab 40 mg (n=327) every other week; upadacitinib 15 mg (n=651) once daily; or placebo (n=651); for up to 26 weeks. They used a treat-to-target design, implementing blinded switching of patients from one therapy to the other prior to 26 weeks if they were non-responders, and at week 26 if they were incomplete responders. Switches were done immediately, without a washout period.

Overall, a total of 252 patients who started on upadacitinib (39%) and 159 patients (49%) who started on adalimumab got switched to the other therapy due to nonresponse or incomplete response.

Both groups of patients who switched from one therapy to the other achieved improvements in disease activity at three and six months after the switch, the study found.

"Whichever mechanism of action one choses, if the desired state is not reached, again by a maximum of six months, it is reasonable to immediately switch to the alternative mechanism of action," said lead study author Dr. Roy Fleischmann, co-medical director of the Metroplex Clinical Research Center and a clinical professor of medicine at the University of Texas Southwestern Medical Center in Dallas.

"This is infrequently done in clinical practice but should become the standard as to how we treat patients with rheumatoid arthritis, assuming there are no co-morbidities or other factors which preclude this," Dr. Fleishmann said by email.

Participants were classified as non-responders if they didn't achieve at least 20% improvement in both tender and swollen joint counts. They were classified as incomplete responders if they had a Clinical Disease Activity Index Score (CDAI) greater than 10 at week 26.

Six months after incomplete responders switched medications, 45% who changed to adalimumab and 58% who changed to upadacitinib had low disease activity, with CDAI scores below 10.

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And, six months after non-responders switched therapies, 36% who changed to adalimumab and 47% who changed to upadacitinib had low disease activity.

A total of 210 patients who were non-responders on initial therapy were also non-responders after switching, including 21% initially randomized to upadacitinib and 22% initially randomized to adalimumab.

There were no deaths or serious adverse events, and the proportion of participants experiencing treatment-related events was similar regardless of whether patients switched to upadacitinib or adalimumab, the study team reports in Annals of the Rheumatic Diseases.

Among the groups of patients who switched therapies, there also was no difference in the frequency of herpes zoster or infections.

One limitation of the study is that the safety and efficacy analysis was limited by the small number of participants who met the criteria for switching therapy. The study wasn't designed to determine statistically significant differences between the two groups that switched therapies or between non-responders and incomplete responders, the researchers also note.

The lack of follow-up data beyond six months may also fail to identify safety issues with switching, said Dr. Jasvinder Singh, a professor of medicine and epidemiology at the University of Alabama at Birmingham and a staff physician at the Birmingham Veterans Affairs Medical Center.

"More safety data are needed with real-world populations with these switches," Dr. Singh, who wasn't involved in the study, said by email.

However, the study results do suggest that switching may benefit some patients, Dr. Singh added.

"Patients who don't respond to either drug and have an incomplete response to methotrexate, can be switched to the other medication for incomplete response or non-response, with encouraging rates of response," Dr. Singh said.

—Lisa Rapaport

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