Background/Purpose: To assess the safety and efficacy of repeated infusions of rituximab (RTX) in patients with primary Sjögren syndrome (PSS).

Methods: Patients with PSS were selected for RTX treatment in case of severe glandular disease or any potentially threatening extra-glandular manifestations. Patients received 2 doses of 1000 mg RTX with a 2-week interval. RTX courses were thereafter programmed every 6 months, for 2 years. The patients were evaluated every 3 months. Criteria for discontinuation were disease progression, appearance of adverse events or inactive disease. At baseline, activity measures and B cell subsets in peripheral blood were studied. Global disease activity was scored with ESSDAI. Descriptive data are expressed in average (limits). Statistical differences between baseline and final measures and the association of disease characteristics at baseline with a favorable outcome were analyzed with non-parametric tests.

Results: 12 patients (11 women) fulfilling inclusion criteria, with a mean age of 60 (42-82) year-old and disease duration of 5.9 (1 – 16) years have been enrolled. Eleven patients had extra-glandular active disease at baseline, consisting of arthritis (6 p), ILD (6 p), Raynaud’s phenomenon (5 p), peripheral neuropathy (3 p), and exanthema (3 p). Anti-Ro antibodies were positive in 10 cases, anti-La were found in 4 and rheumatoid factor in 6 cases. At baseline, global B cell counts were within normal range, with a prominent shift towards naïve cells (68% of all CD19+ cells). Interestingly, this appeared to be a favorable marker, since percentage of naïve cells was negative correlated with RF titers (rho -0.84, p < 0.02) and was significantly associated to prednisone dose reduction at end points (rho 0.983, p < 0.005).

The patients have received a total dose of 42500 mg RTX, 3750 mg (500 – 6000) per patient, over an observation period of 13 (3 – 23) months. During this period, 2 treatments were withdrawn, 1 due to an acute Epstein Barr virus infection at the first RTX course and the second one due to sustained remission. Two additional infections were observed during follow-up, neither of them leading to discontinuation.  At endpoints, daily prednisone was tapered in 10 mg/d (Z -2.2, p 0.028). The average ESSDAI dropped from 4.1 (1-9) to 2.2 (0 – 4), Z -2.33, p 0.02, and showed an adjusted change of -4.22 points per year of follow-up. The change in ESSDAI was correlated to the cumulative dose of RTX (rho 0.665, p < 0.02). Reduction of prednisone was positively correlated to the number of RTX courses and the cumulative dose of RTX. Finally, no reconstitution of the B cell subpopulations has been found over the observation period.

Conclusion:

In this cohort of patients with Sjögren’s syndrome, RTX showed a favorable safety profile as well as a possible benefit in the short-term control of the process. Although these results should be taken with caution, they suggest that B cell depletion can fill a gap in the management of difficult to treat Sjögren’s syndrome.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-repeated-infusions-of-rituximab-in-patients-with-primary-sjogrens-syndrome/