Background Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, with basically symptomatic treatment and use of conventional DMARDs on off-label use. Cyclosporine A (CyA), an approved DMARD for treatment of different rheumatic disorders, is mainly used as local treatment of keratoconjunctivitis sicca in pSS, whereas reports on systemic effects are limited to small cohorts so far. Low-dose CyA has shown promising effects and good tolerability in other autoimmune disorders [1, 2, 3].
Objectives To investigate the effects of a reduced dosage of CyA on articular involvement in patients with pSS.
Methods For this investigator initiated single-center, open-label, non-controlled phase II trial 30 patients with pSS fulfilling the European-American Classification Criteria were included. Patients had to have active articular involvement defined as a minimum of 3 tender and/or 3 swollen joints. Oral NSAIDs and systemic steroids (<10mg/d prednisone equivalent) were permitted at stable doses. Primary endpoint was to evaluate the therapeutic effects of low-dose CyA (2mg/kg divided in two intakes a day) on articular involvement (reduction of tender and swollen joint counts) after 16 weeks of treatment.
Results 30 patients (29 female) with an average age of 55 years and mean disease duration of 6 years were included. In 20 patients at least one DMARD (not CyA) had failed prior to study entry. Treatment with low-dose CyA improved significantly articular involvement in patients with pSS. At week 16, Tender Joint Count (/68) decreased by 7 joints (from 16±13 to 9±11; p=0.002), Swollen Joint Count (/66) decreased by 2 joints (from 3±3 to 1±3; p<0.001) and DAS28 improved by 0.8 (from 5.0 to 4.2; p<0.001). Furthermore, a considerable treatment effect was observed on overall disease activity by the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) with a reduction from 5.5±3.4 to 3.8±4.3 (p=0.02). IgG-levels decreased by 0.5g/l (p=0.008). Ultrasonography of the three predominantly affected joints confirmed improvement of joint effusion and synovialitis at week 16. CRP, ESR, sicca-symptoms, HAQ, Patient's VAS-global assessment and -Pain decreased though without statistical significance. Overall, the treatment was well tolerated and adverse events were consistent with the known safety profile of CyA (e. g. hypertension, headache, discrete creatinine increase).
Conclusions This pilot-study indicates promising effects of low-dose CyA treatment on articular involvement and disease activity in patients with pSS. The safety profile was comparable to known side effects of CyA.
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Vescovi P et al. Sjogren's syndrome: clinical and therapeutic features. A review of the literature. Minerva stomatologica. 2004 Jan-Feb.
Zeidler HK et al. Progression of joint damage in early active severe rheumatoid arthritis during 18 months of treatment: comparison of low-dose cyclosporin and parenteral gold. British journal of rheumatology. 1998 Aug.
Acknowledgements This IIT was supported by Novartis Germany
Disclosure of Interest None declared