Long term cholesterol lowering therapy does not interfere with clinical response to anti CD20 therapy in patients with rheumatoid arthritis

      Objective: Cholesterol lowering therapy was reported to inhibit rituximab (RTX) clinical efficacy in lymphoma and rheumatoid arthritis (RA). For a short period of treatment (6 months), this effect has not been proved. The objective of our study was to asses if long term cholesterol lowering therapy with statins, which may influence long time (18 months) clinical response in patients with RA treated with RTX. Methods: Starting from February 2010, all patients initiating RTX treatment in Sfanta Maria Hospital, Bucharest, were included in this prospective cohort study (total number 82). All patients had high disease activity RA, failure to at least one anti TNF and consecutively switched to anti CD20 therapy with RTX associated with Disease Modifying Antirheumatic Drugs (DMARD) (i.e. methotrexat, sulfasalasine, hidroxichloroquine). RTX was administered intravenously as two 1 g infusions given with standardized premedication, separated by an interval of two weeks. Biological tests [i.e. erythrocyte sedimentation rate (ESR), C reactive protein (CRP)], clinical disease activity markers (i.e. number of swollen and tender joints) and composite scores [i.e. Disease Activity Score based on 28 joints counts (DAS28) visual analogue scale, and European League Against Rheumatism (EULAR) response criteria] were provided at every 3 months. Total cholesterol level and statin treatment were monitored. The statin treatment was initiated according to national guideline. For the final analysis, we excluded patients that discontinued statin treatment or had associated statin after RTX was initiated. Results: 45 patients fulfilled criteria for the final analysis: 20 patients had statin associated to RTX. DAS 28 scores, CRP levels and ESR levels of both groups were similar at baseline. Patients exposed to statins were significantly older than unexposed patients (p = 0.017). Clinical outcome was evaluated using DAS28 and EULAR response, both measured at 6, 12 and 18 months. A tendency of increasing in DAS28 score was observed in the statin-exposed group, but statistical tests (Student t-test) showed no significant difference for DAS28 score on follow up, with p values >0.05 (at 6 months p = 0.777, at 12 months p = 0.303 and at 18 months p = 0.136). The statin-exposed status was negatively correlated to EULAR response at 6 months (r = −0.073, p = 0.661) and 18 months (r = −0.197, p = 0.244), but the correlation was very weak and with no statistical significance. Conclusions: Even though cholesterol depletion may influence the integrity of lipid rafts in the cell membrane, consecutively inhibiting hypercrosslinking of CD20 molecules with RTX, long term inhibitory effects of statins on RTX treatment in RA patients have not been proven. As far as we know, long term impact has not previously been studied. More studies are required regarding this possibility.
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