Effect of etanercept in polymyalgia rheumatica: a randomized controlled trial

Abstract

Introduction: To 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.

Methods: Twenty 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.

Results: At 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.

Conclusions: Etanercept 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 registration: ClinicalTrials.gov (NCT00524381).

Figures

Figure 1

Flow of patients and controls through the trial. This includes randomization, withdrawal numbers and reasons, and number of participants, who completed the study.

Figure 2

Primary outcome. Polymyalgia rheumatica activity score (PMR-AS) in 20 patients with PMR and 20 non-PMR control subjects at baseline (black bars) and after (white bars) 14 days of treatment with etanercept or placebo. PMR-AS is calculated from the blood level of C-reactive protein, duration of morning stiffness, subject's assessment of pain (visual analog score (VAS)), physician's global assessment (VAS), and the subject's ability to elevate the arms (see text). Δ all values in control subjects significantly different (P < 0.0001 to 0.01) from values in patients.

Figure 3

Clinical and paraclinical measurements in patients with polymyalgia rheumatica at baseline (black bars) and after (white bars) 14 days of treatment with etanercept or placebo. C-reactive protein (CRP), patients' ability to elevate the arms (E, 3 to 0: 3 = no elevation possible; 2 = elevation possible below shoulder height; 1 = elevation possible above shoulder height; 0 = full elevation possible), the physician's global assessment (visual analog score, VAS), and erythrocyte sedimentation rate (ESR).

Figure 4

Plasma IL-6 concentrations in patients with polymyalgia rheumatica (PMR) and non-PMR control subjects at baseline (black bars) and after (white bars) 14 days of treatment with etanercept or placebo. Δ all values in control subjects significantly different (P < 0.01 to 0.001) from values in patients.

Figure 5

Plasma TNF-α concentrations in patients with polymyalgia rheumatica (PMR) and non-PMR control subjects at baseline (black bars) and after (white bars) 14 days of treatment with etanercept or placebo.