Abstract
ObjectivesFatigue is a major cause of disability in primary Sjögren's syndrome (pSS). Fatigue has similarities with sickness behaviour in animals; the latter mediated by pro-inflammatory cytokines, in particular interleukin (IL)-1, acting on neuronal brain cells. We hypothesised that IL-1 inhibition might improve fatigue in pSS patients; thus, we examined the effects and safety of an IL-1 receptor antagonist (anakinra) on fatigue.MethodsTwenty-six pSS patients participated in a double-blind, placebo-controlled parallel group study. Patients were randomised to receive either anakinra or a placebo for four weeks. Fatigue was evaluated by a fatigue visual analogue scale and the Fatigue Severity Scale. The primary outcome measure was a group-wise comparison of the fatigue scores at week 4, adjusted for baseline values. Secondary outcome measures included evaluation of laboratory results and safety. The proportion of patients in each group who experienced a 50% reduction in fatigue was regarded as a post-hoc outcome. All outcomes were measured at week 4.ResultsThere was no significant difference between the groups in fatigue scores at week 4 compared to baseline after treatment with anakinra. However, six out of 12 patients on anakinra versus one out of 13 patients on the placebo reported a 50% reduction in fatigue VAS (p = 0.03). There were two serious adverse events in each group.ConclusionsThis randomised, double-blind, placebo-controlled trial of IL-1 blockade did not find a significant reduction in fatigue in pSS in its primary endpoint. A 50% reduction in fatigue was analysed post-hoc, and significantly more patients on the active drug than on placebo reached this endpoint. Although not supported by the primary endpoint, this may indicate that IL-1 inhibition influences fatigue in patients with pSS.Trial registrationClinicalTrials.gov NCT00683345
Highlights
Primary Sjogren’s syndrome is a chronic autoimmune disease with an estimated prevalence of 0.05%–0.5% [1,2]
We recently demonstrated that increased activation in the IL-1 system, as detected by raised levels of IL-1 receptor antagonist (IL-1Ra) in cerebrospinal fluid (CSF), is associated with more fatigue in Primary Sjogren’s syndrome (pSS) [7]
There was no significant difference between the groups in fatigue score at week 4 when adjusting for baseline values, p = 0.19 (ANCOVA)
Summary
Primary Sjogren’s syndrome (pSS) is a chronic autoimmune disease with an estimated prevalence of 0.05%–0.5% [1,2]. The majority of patients have autoantibodies against the ribonuclein particles SSA/Ro and/or SSB/La. Patients frequently have extraglandular manifestations such as muscle and joint pain, neuropathy, and fatigue [4]. Fatigue is a major cause of disability [5]. It was reported that 85% of pSS patients experience fatigue, and 40% of the patients report fatigue as their most severe symptom [6]. It is well known that mood disorders influence fatigue, but in pSS fatigue occurs in non-depressed as well as depressed individuals [7,8]. Other factors influencing fatigue in pSS are pain, sleep disorders, learned helplessness, and possibly neuroendocrine disturbances and autonomic dysfunction [9]
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