Factors Predictive of Sustained Rituximab Response in Primary Sjögren Syndrome Identified by Study

About 43% of patients experienced complete depletion of B cells after the first round of rituximab, and those patients had greater odds of longer-term success.

Patients with systemic manifestations of primary Sjögren syndrome (pSS) tend to do better on repeat cycles of Rituxan (rituximab) if they are coprescribed immunosuppressant therapy and if they achieve complete B-cell depletion, according to a new report.

The study found that about 1 in 6 patients will have secondary nondepletion and nonresponse (2NDNR) in repeat cycles of rituximab. The findings were published in ACR Open Rheumatology.

The authors noted that B cells play a pathogenetic role in the development of pSS, making B-cell–targeted therapies like rituximab a “logical” treatment choice. Yet, they said the data on rituximab’s efficacy in pSS is mixed, with 2 prominent trials failing to meet their primary end points despite the therapy’s apparent efficacy in a subset of patients. In related diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), the authors said B-cell depletion appeared to be linked with clinical response to rituximab. But they also said there are no documented B-cell biomarkers for pSS to date.

Further complicating the matter is the phenomenon of 2NDNR in which some patients who initially responded to rituximab later experienced severe infusion reactions, a failure to completely deplete CD20-positive B cells, and a lack of clinical response.

The investigators wanted to see if they could identify factors that might predict clinical response to repeat cycles of rituximab in patients with pSS. They retrospectively analyzed 40 patients who had been treated with rituximab for pSS. Clinical responses were measured by comparing European League Against Rheumatism Sjögren Disease Activity Index (ESSDAI) scores at baseline and at 6 months. Peripheral B cells were assessed using highly sensitive flow cytometry. The cohort contained 169 cycles of rituximab over a follow-up of 165 patient-years.

At baseline, most patients (n = 38) had ESSDAI scores above 5 and 28 were taking concomitant immunosuppressants. The articular domain was most commonly involved in the cases (73%), followed by the mucocutaneous (23%), hematological (20%), and nervous system (18%) domains.

In the first cycle of treatment, 73% had a response according to ESSDAI. Twenty-three of those patients received another round of treatment after clinical relapse, and about 65% responded. The other 8 patients experienced 2NDNR. Thirteen patients discontinued therapy within the first 2 cycles. Fifty-seven percent of patients were still on rituximab at 5 years.

Although the majority of patients responded to rituximab, the investigators found that only 17 patients (43.6%) achieved a complete depletion of B cells within their first 2 weeks of rituximab therapy. That metric appeared to be predictive of which patients were most likely to be successful on repeat cycles of rituximab (odds ratio [OR], 9.78; 95% CI, 1.32-72.25).

“This is the first study to show that achieving complete depletion after 1 rituximab infusion was associated with a superior outcome in pSS and concurred with our findings and others in RA,” the investigators wrote.

In addition, the analysis showed that taking a concomitant immunosuppressive therapy boosted the odds of response to rituximab (OR, 7.16; 95% CI, 1.37-37.35).

The authors said the data overall suggest rituximab can be an effective therapy in pSS, particularly when administered along with an oral immunosuppressant.

“In conclusion, treatment for systemic manifestations of pSS with rituximab is highly effective and can be guided by B-cell monitoring, with the aim of achieving complete depletion,” they wrote.

Reference:

Pepple S, Arnold J, Vital EM, et al. Predicting sustained clinical response to rituximab in moderate to severe systemic manifestations of primary Sjögren syndrome. ACR Open Rheumatol. Published online June 5, 2022. doi:10.1002/acr2.11466