Primary Sjögren’s syndrome: Extraglandular manifestations and hydroxychloroquine therapy

Abstract

The use of hydroxychloroquine (HCQ) in Primary Sjögren's Syndrome (pSS) has been assessed in different studies over the last years, with conflicting results regarding its efficacy in sicca syndrome and extraglandular manifestations (EGM). The goal of this study was to compare the incidence rate of EGM in pSS patients with and without HCQ therapy.We performed a multicenter retrospective study, including patients with pSS (European classification criteria) with at least 1 year of follow-up. Subjects with concomitant fibromyalgia, autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis were excluded. Demographics and pSS characteristics were recorded. The EGM were defined by EULAR-SS disease activity index (ESSDAI). Patients were divided into two groups according to their use or not of HCQ therapy. We evaluated the use of HCQ and its relationship to EGM. HCQ therapy was defined as the continuous use of the drug for at least 3 months. A descriptive analysis of demographics and pSS characteristics was performed. We compared the incidence of EGM between groups defined by HCQ therapy using chi test or Fisher's exact test. A total of 221 patients were included (97.3% women), mean age, 55.7 years (SD 14). Mean age at diagnosis, 48.8 years (SD 15); median disease duration, 60 months (IQR 35-84). One hundred and seventy patients (77%) received HCQ. About half of the patients had at least one EGM during the course of the disease, 20% of them developed an EGM before the onset of the sicca syndrome and 26% simultaneously with dryness symptom. Overall, EGM were less frequent in those on HCQ therapy (36.5% vs 63.5%, p < 0.001). Considering each EGM individually, the following manifestations were more frequent in the non-treated group: arthritis (p < 0.001), fatigue (p < 0.001), purpura (p = 0.01), Raynaud phenomenon (p = 0.003), and hypergammaglobulinemia (p = 0.006). Immunosuppressive treatment was indicated on 28 patients (12.7%), 13 of which were receiving also HCQ. The first reason for those treatments was the presence of arthritis in 12/28 patients (42.8%), and the drug used in all the cases was methotrexate. Only three patients required immunosuppressive therapy with cyclophosphamide, due to the presence of glomerulonephritis, vasculitis, and interstitial lung disease. None of the patients received biologic therapy. The lower incidence of EGM was observed in patients on HCQ therapy supports its efficacy in pSS. However, further large scale prospective studies are needed to confirm these findings.

Efficacy and safety of abatacept in active primary Sjögren’s syndrome: results of a phase III, randomised, placebo-controlled trial

“…8 There are currently no approved diseasemodifying treatments for pSS. Small, open-label, uncontrolled and controlled clinical efficacy studies of methotrexate, 9 leflunomide, 10 hydroxychloroquine, 11 rituximab, [12][13][14] epratuzumab (B-celltargeted agents), 15 belimumab (B-cell-activating factor-blocking agent) 16 What does this study add? ► Abatacept treatment did not result in significant clinical efficacy versus placebo in this randomised controlled trial, but it showed evidence of disease-relevant biological activity.…”

Pulmonary and Bronchiolar Involvement in Sjogren's Syndrome

“…292 EGMs were less frequent in those treated with HCQ (36.5 vs. 63.5%, p < 0.01). 292 Furthermore, the following manifestations were more common in the untreated group: arthritis (p < 0.001); fatigue (p < 0.01); purpura p ¼ 0.01); RP (p ¼ 0.003); and hypergammaglobulinemia (p ¼ 0.006). Immunosuppressive agents were used in 28 (12.7%), 13 of who were receiving HCQ.…”

“…Optimal treatment of SS is controversial, as a paucity of RCTs has been done. 289 Corticosteroids (CS), immunosuppressive agents (IA), 290 disease modifying antirheumatic drugs (DMARD), 2,290 and hydroxychloroquine (HCQ) [291][292][293] are often used 294 (►Table 3), but appropriate indications have not been ascertained. Unequivocal responses to systemic CS or IA have been noted in some patients with SS and extraglandular involvement.…”

“…296 Topical agents are typically used for ophthalmologic manifestations 68,297 ; HCQ is also often used in that context. 291,292 In a multicenter retrospective study of 221 patients with pSS, HCQ was used in 177 (77%). 292 EGMs were less frequent in those treated with HCQ (36.5 vs. 63.5%, p < 0.01).…”

“…291,292 In a multicenter retrospective study of 221 patients with pSS, HCQ was used in 177 (77%). 292 EGMs were less frequent in those treated with HCQ (36.5 vs. 63.5%, p < 0.01). 292 Furthermore, the following manifestations were more common in the untreated group: arthritis (p < 0.001); fatigue (p < 0.01); purpura p ¼ 0.01); RP (p ¼ 0.003); and hypergammaglobulinemia (p ¼ 0.006).…”