Rituximab is a safe and effective treatment for the systemic complications of primary Sjögren's syndrome, judging from the findings of a small retrospective study.
Recent investigations have linked high levels of B-cell autoreactivity with high levels of disease activity and the development of a range of systemic complications, including arthritis; vasculitis; lymph node enlargement; thyroid, lung, kidney, nerve, and muscle problems; and an increased risk of developing B-cell lymphoma.
To assess the safety and efficacy of rituximab (Rituxan), an anti-CD20 antibody that targets B cells, for treating the systemic manifestations of primary Sjögren's syndrome (pSS), Dr. Raphaéle Seror of Bicetre Hospital, Paris, and colleagues obtained records from six referral centers in France for 16 female patients (median age 59 years) diagnosed with the condition who had been treated with rituximab for either lymphoma or other complications (Ann. Rheum. Dis. 2006 Sept. 1 [Epub doi:10:1136/ard.2006.057919]).
All of the patients included in the evaluation received a 100-mg pulse of methylprednisone and either 20 mg of oral cetirizine or an intravenous pulse of 5-mg dexchlorpheniramine before each rituximab infusion, and four of the patients received concomitant immunosuppressants.
Rituximab therapy induced complete remission in four of the five lymphoma patients but was not effective in one patient with salivary lymphoma. Among the 11 patients with systemic features, rituximab was effective in 9, including 4 with cryoglobulinemia, 2 with pulmonary involvement and polysynovitis, 2 with polysynovitis, and 1 with mononeuritis multiplex. Despite rituximab therapy, one patient with cryoglobulinemia experienced a worsening of peripheral nerve involvement, and the platelet counts of the patient with thrombocytopenia remained below 10,000/mm
The investigators also assessed laboratory outcomes, including changes in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, cryoglobulinemia, B-cell biomarkers, and, for some patients, serum B-cell activating factor of the tumor necrosis factor family (BAFF) levels from retrospective ELISA assessment of frozen samples. B-cell depletion was achieved in 14 of the 15 patients, and median ESR and CRP levels decreased from 60 to 20 mm/h and from 11.4 to 4 mg/L, respectively.
Median rheumatoid factor decreased from 124 to 7.5 IU/mL, disappearing completely in five patients. Median gammaglobulin, IgG, and beta-2 microglobulin levels also decreased, while median BAFF levels increased, possibly as a consequence of B-cell depletion, the authors hypothesized.
During the median 14.5-month follow-up, five patients relapsed, four experienced a flare of pSS, and lymphoma was diagnosed in one patient treated initially for cryoglobulinemia. Clinical relapse was associated with the reappearance within 3 months prior to relapse of peripheral blood B cells and an increase in B-cell biomarkers. Rituximab was effective in all but four of five patients treated for relapse. Only three of the patients experienced moderate adverse events, including delayed, infusion-related flulike reactions, the authors wrote.