U.K. Study Rejects Rituximab for Sjogren’s

A British study finds that rituximab is "neither clinically or cost-effective" in a study of patients with primary Sjogren’s syndrome who were being treated for fatigue and oral dryness.

These findings differ from the newly issued treatment guidelines for Sjogren's syndrome in the U.S. in which the Sjogren’s Syndrome Foundation recommends the use of rituximab for patients with oral dryness. However, for fatigue, the foundation strongly recommended exercise. The guidelines were based on a review of published studies, case reports and input from both physicians and patients.

In the new study, which was accepted for publication on March 7 in the journal Arthritis & Rheumatology, researchers led by Simon J. Bowman, Ph.D., of University Hospitals Birmingham NHS Foundation Trust in the United Kingdom, conducted a randomized, double-blind, placebo-controlled trial (referred to as the TRACTISS trial ) of 133 patients from 25 clinics with primary Sjogren’s syndrome.

This trial enrolled Sjogren’s patients who suffered from symptomatic fatigue and oral dryness. They received two doses of 1,000 mg rituximab, but at the 48-week assessment, patients did not report having a response to treatment that was considered significant (30% reduction from baseline of Oral Dryness or Fatigue VAS) as compared to those in the placebo group.

“These and other patient-reported outcomes of Ocular and Overall Dryness, Joint Pain and Global Assessment of disease activity were not significantly improved by rituximab at any time-point,” the researchers wrote. “We also did not observe a significant benefit in terms of lachrymal flow, or in any of the composite patient-reported outcomes, or disease activity indices, except for a one-off significant difference between groups in the ESSDAI score at week 36.”

Composite disease activity scores, and patient-reported outcome measures confirmed no benefit for rituximab. There was no improvement in any domain of the SF-36 for rituximab over placebo, or in the SF-36 component scores. There was also no improvement in the PROFAD-SSI domains at any time-point for rituximab compared to placebo.

There were slightly more adverse events reported in total for rituximab, but no difference in serious adverse events (ten in each group). 

"Although there did not appear to be any excess risk due to rituximab, the results of the TRACTISS trial do not support the general use of rituximab in treating PSS, particularly in patients with recent disease onset and / or low disease activity," the authors wrote. "Rituximab may still have a role in treating PSS patients with high levels of systemic disease activity who have failed to improve following conventional immunosuppressive therapy."

TRACTISS is the fourth, double-blind, placebo-controlled, randomized trial of rituximab. The first study, a pilot in 17 patients, reported a greater reduction in fatigue among patients randomized to rituximab, but it wasn’t sustained. The TEARS study analyzed 120 patients randomized to either rituximab or placebo. A significant response was detected at six weeks, particularly in fatigue, but it wasn’t sustained at 24 weeks.

“Although there did not appear to be any excess risk due to rituximab, the results of the TRACTISS trial do not support the general use of rituximab in treating primary Sjogren’s syndrome, particularly in patients with recent disease onset and/or low disease activity,” the researchers wrote. “Rituximab may still have a role in treating these patients with high levels of systemic disease activity who have failed to improve following conventional immunosuppressive therapy.”

Disclosures:

The study was funded by Arthritis Research UK. Hoffman La Roche provided rituximab free of charge to the study. Hoffman La Roche was permitted to review results prior to submission, but final decision on content and publication remained with the authors. 

References:

Simon J Bowman PhD, Colin C Everett, John L O’Dwyer, et al. "Randomized Controlled Trial of Rituximab and cost effectiveness analysis in treating fatigue and oral dryness in primary Sjogren’s Syndrome," Accepted Article for publication March 7, 2017. Arthritis & Rheumatology. DOI 10.1002/art.40093