Rituximab Only Modestly Beneficial in Primary Sjögren's Syndrome

February 01, 2013

NEW YORK (Reuters Health) Feb 01 - A single course of rituximab affords only modest clinical benefit to patients with primary Sjögren's syndrome, according to a small study from the Autoimmunity Centers of Excellence.

No drugs have been shown to reduce disease activity or prevent damage in patients with primary Sjögren's syndrome, but abnormal B responses appear to play an important role in its pathophysiology. For that reason, potent B cell depleters like rituximab might offer hope.

In a phase I study in 12 patients, Dr. E. William St. Clair from Duke University Medical Center, Durham, North Carolina, and colleagues evaluated the safety and possible clinical efficacy of rituximab (two 1000-mg infusions two weeks apart) in primary Sjögren's syndrome and its effects on blood B cell subsets, autoantibodies, cytokines, and gene transcripts.

Patients were followed for 52 weeks.

As reported online January 17 in Arthritis & Rheumatism, clinical improvements were modest but statistically significant in global ratings of disease activity by both the physicians (median improvement, 26 mm on 100-mm visual analog scale; p=0.012) and the patients (median improvement, 8.5 mm; p=0.009).

Improvements in tongue dryness, thirst, oral discomfort, and overall fatigue were statistically significant, albeit modest, but there were no significant improvements in joint pain, stimulated and unstimulated whole salivary flow, tear production, or ocular surface dryness.

"These results are consistent with those reported in an abstract describing the results of a 122-patient, randomized, placebo-controlled study of rituximab therapy in primary Sjögren's syndrome," the investigators say.

These modest improvements came in the setting of greater than 95% depletion of blood B cells in all 12 patients by week 8 or 14.

Rituximab did not bring substantial changes in the number or percentages of blood T and NK cells or monocytes or in serum levels of anti-RO/SSA, anti-La/SSB, or anti-MR3 antibodies.

Expression of several B-related genes decreased after rituximab therapy and returned toward baseline by week 52.

Because three patients experienced unexpected grade 2 reactions to vaccines after rituximab treatment, no subsequent vaccinations were administered. One case of squamous cell carcinoma 301 days after administration of rituximab was considered "possibly related" to the study drug. Rituximab was otherwise well tolerated.

"Importantly," the researchers note, "we did not detect any unexpected safety signals, except for the possibility of exaggerated vaccine reactions."

Despite the limited benefits in this small study, the authors argue against abandoning research on rituximab for these patients. "Larger randomized, placebo-controlled clinical trials...are needed to further evaluate the clinical efficacy and safety of rituximab therapy for primary Sjögren's syndrome," they conclude.

The authors did not respond to a request for comment.

SOURCE: http://bit.ly/Tn5JyJ

Arthritis Rheum 2013.