Background/Purpose:

Hydroxychloroquine (HQ, Plaquenil) is often prescribed in patients with primary Sjögren’s syndrome (pSS), notably for arthralgias, synovitis or purpura, but also only for dryness and fatigue. Thus, at enrollment in the “Assessment of Systemic Signs and Evolution of primary Sjögren’s Syndrome”’ (ASSESS) prospective cohort, 56% of the 395 patients had been or were treated with HQ. However, except a crossover trial which included 19 patients, no controlled trial has ever evaluated HQ versus placebo.  We therefore conducted a multicenter, randomized, double-blind, placebo-controlled trial (NCT00632866, Randomized Evaluation of hydroxychloroQUine in primary sJOgren’s syndrome, JOQUER).  

Methods:

A total of 120 patients with pSS were randomly assigned to receive HQ (400 mg/j) or placebo and were followed up for 24 weeks. All patients fulfilled the European American consensus group criteria. A favorable overall response (primary outcome criteria) was defined as the patient having at least a 30% improvement between weeks 0 and 24 in the values on 2 of  3 patient’s  visual analogic scales (VAS) evaluating dryness, pain and fatigue. Secondary end points were the evolution of Eular Sjögren’s Syndrome Disease Activity Index (ESSDAI), Eular Sjögren’s Syndrome Patient-Related Index (ESSPRI), dryness (Schirmer’s test and unstimulated salivary flow), serum gammaglobulin levels, and of questionnaires of quality of life and symptoms  (SF-36, HAD, PROFAD, SSI).   

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%, median ESSDAI: 2, proportion of patients with systemic involvement at enrollment: 30%, median ESSPRI: 6.3.

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). No significant difference was observed in the evolution of systemic disease activity, dryness, symptoms and quality of life. No significant difference was observed in patients with anti-SSA autoantibodies, high IgG levels, or systemic involvement at enrollment. In patients treated with HQ, a trend towards a decrease of serum IgG was observed (from 14.5 at enrollment to 13.4g/l at week 24 in the HQ arm and from 14.2 to 14.0 g/l in the placebo arm (p= 0.1), as well as a significant decrease of IgM (from 1.3 to 1.1 g/l under HQ and stable level at 1.4 g/l under placebo, p= 0.01).  In the HQ arm, all except 1 of the evaluated patients had detectable blood levels of HQ at 6 months. Tolerance of HQ was comparable to placebo.

Conclusion:

The results of this randomized, double-blind, placebo-controlled trial, did not show any evidence of short term efficacy of hydroxychloroquine in pSS. Analyzes are ongoing to determine whether HQ could have a therapeutic interest in some patients with an interferon signature.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/inefficacy-of-hydroxychoroquine-in-primary-sjogrens-syndrome-results-of-the-joquer-randomized-placebo-controlled-trial-in-primary-sjogrens-syndrome/