Effect of etanercept in polymyalgia rheumatica: a randomized controlled trial

Abstract

IntroductionTo elucidate in polymyalgia rheumatica (PMR) the role of tumor necrosis factor (TNF) α and the therapeutic potential of blockade with soluble TNF-α receptor, we carried out the first randomized controlled trial with etanercept in PMR.MethodsTwenty newly diagnosed, glucocorticoid (GC) naïve patients with PMR and 20 matched non-PMR control subjects completed the trial. Subjects were randomized in a 1:1 ratio to monotherapy with etanercept (25 mg s.c. biweekly) or placebo (saline) for 14 days. Study outcomes were assessed at baseline and after 14 days. The primary outcome was the change in PMR activity score (PMR-AS). Secondary outcomes were: changes in erythrocyte sedimentation rate (ESR) and plasma levels of TNF-α and interleukin (IL) 6; patients' functional status (health assessment questionnaire) and cumulative tramadol intake during the trial.ResultsAt baseline, plasma TNF-α was higher in patients than in controls (P < 0.05). The concentration always increased with etanercept treatment (P < 0.05). In patients, etanercept decreased PMR-AS by 24% (P = 0.011), reflecting significant improvements in shoulder mobility, physician's global assessment and C-reactive protein, and insignificant (P > 0.05) improvements in duration of morning stiffness and patient's assessment of pain. In parallel, ESR and IL-6 were reduced (P < 0.05). Placebo treatment did not change PMR-AS, ESR and IL-6 (P > 0.05). Functional status did not change and tramadol intake did not differ between patient groups. In controls, no changes occurred in both groups.ConclusionsEtanercept monotherapy ameliorates disease activity in GC naïve patients with PMR. However, the effect is modest, indicating a minor role of TNF-α in PMR.Trial registrationClinicalTrials.gov (NCT00524381).

Tumor Necrosis Factor Inhibits Glucocorticoid Receptor Function in Mice

“…The strong pro-inflammatory nature of TNF␣ is also manifested in the pathogenesis of many inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel diseases, asthma, and psoriasis (2)(3)(4). Therefore, several of these pathologies are currently treated with TNF␣ inhibitors (5,6). However, these anti-TNF␣ molecules are very expensive, they cause many side effects, e.g.…”

Outcome Measures in Polymyalgia Rheumatica. A Systematic Review

“…The electronic search strategy yielded 868 articles, 43 of which were selected, on the basis of title and abstract, for further assessment/detailed review. Ultimately, 35 studies [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]42,43,44,45,46 met inclusion criteria for this systematic review (Figure 1). Agreement between the 2 reviewers was 96.6% and 100% for the first and second steps of article selection, respectively.…”

“…Table 1 shows the study design characteristics of included articles. Twelve of the included studies are randomized drug trials, controlled against either placebo or conventional PMR treatment [12][13][14][15][16][17][18][19][20][21]22,23 . Three are nonrandomized interventional studies or ones without clear information about randomization 24,25,26 .…”

“…Pain. Pain was used as an outcome in 17 studies 12,13,14,15,16,18,19,22,25,34,36,39,40,43,44,45,46 . A visual analog scale (VAS)…”

“…Morning stiffness. Stiffness, more commonly morning stiffness, was considered in almost all the included studies 13,14,15,16,18,19,20,21,22,24,25,26,27,28,30,33,34,35,36,37,38,40,43,44,45,46 . It was evaluated as an independent outcome in 11 studies 13,14,15,16,18,19,25,27,34,40,44 , and was included as a variable in composite disease activity scores or in the definition of relapse/recurrence/remission in an additional 15 studies 19,20,22,24,26,28,33,35,36,37,38,43,…”