Background Hydroxychloroquine (HQ, Plaquenil) is often prescribed in patients with primary Sjögren’s syndrome (pSS). However, except a crossover trial, no controlled trial has ever evaluated HQ versus placebo.
Methods 120 patients with pSS were randomly assigned to receive HQ (400 mg/j) or placebo for 24 weeks (controlled phase) and were all prescribed HQ between week 24 and week 48 (open extension). All patients fulfilled the AECG criteria. A favorable overall response (primary outcome criteria) was defined as the patient having >or= 30% improvement between weeks 0 and 24 in the values on 2 of the 3 patient’s VAS evaluating dryness, pain and fatigue. Secondary end points were the evolution of the ESSDAI, the ESSPRI, Schirmer’s test and unstimulated salivary flow, serum gammaglobulin levels, and of SF-36, HAD, PROFAD, and SSI. Serum interferon-regulated chemokines (CXCL10, CCL2 and CCL19) were assessed at baseline and W24 in the 45 patients with available serum.
Results Baseline characteristics of the 120 patients were as following: mean age 55.9 years, 91.7% of women, median disease duration: 5 years, anti-SSA positivity : 55.1%, patients with systemic involvement at enrollment: 30%. At 6 months, 19.2% of patients receiving placebo and 19.6% of patients treated with HQ had a favorable overall response (p = 0.9). At 12 months, 18.8% of patients treated for 6 months with placebo, then 6 months with HQ and 32.1% patients treated with 12 months with HQ were responders (p= 0.1). No significant difference was observed in any of the secondary outcome criteria. No significant difference was observed in patients with anti-SSA autoantibodies, high IgG levels, or systemic involvement. In patients treated with HQ, a trend towards a decrease of serum IgG was observed, as well as a significant decrease of IgM. In patients with HQ, a decrease in serum CXCL10 (from 50.5 to 35.8 pg/ml vs from 27.7 to 38.7 pg/ml under placebo, p=0.001) and CCL19 (from 241.6 to 160.9 pg/ml vs from 142.3 to 131.1 pg/ml, p=0.3), but not CCL2, was observed. In the HQ arm, all except 1 had detectable blood levels of HQ at 6 months. Baseline levels of HQ or of IFN-regulated chemokines were not associated with a favorable overall response. Tolerance of HQ was comparable to placebo.
Conclusions The results of this controlled trial did not show any evidence of short term efficacy of HQ in pSS. HQ induced a decrease in serum level of CXCL10 and CCL19, 2 IFN-induced chemokines but no association with response to HQ could be identified in any subgroup of patients.
Disclosure of Interest None Declared