Infliximab plus Prednisone or Placebo plus Prednisone for the Initial Treatment of Polymyalgia Rheumatica

A Randomized Trial

1 May 2007 | Volume 146 Issue 9 | Pages 631-639

Background: A reliable alternative to steroids for treating polymyalgia rheumatica has not yet been identified. Although infliximab has been used occasionally in steroid-resistant cases, its efficacy has not been demonstrated in a controlled study.

Objective: To compare the efficacy of prednisone plus infliximab with that of prednisone plus placebo in patients with newly diagnosed polymyalgia rheumatica.

Design: Randomized, placebo-controlled trial.

Setting: 7 rheumatology clinics in Italy.

Patients: 51 patients with newly diagnosed polymyalgia rheumatica. Patients with associated giant cell arteritis and those who had been previously treated with steroids or biological or immunosuppressive agents were excluded.

Intervention: Initial therapy with oral prednisone tapered from 15 mg/d to 0 mg/d over 16 weeks according to a standard protocol, plus infusions of placebo or infliximab, 3 mg/kg of body weight, at weeks 0, 2, 6, 14, and 22.

Measurements: The primary efficacy end point was the proportion of patients without relapse or recurrence through week 52. Secondary outcomes were the proportion of patients no longer taking prednisone, the number of relapses and recurrences, the duration of prednisone therapy, and the cumulative prednisone dose.

Results: Four patients (3 in the infliximab group and 1 in the placebo group) did not complete the trial. The proportion of patients who were free of relapse and recurrence at 52 weeks did not differ between groups (6 of 20 patients [30%] in the infliximab group vs. 10 of 27 patients [37%] in the placebo group; adjusted risk difference, –3 percentage points [95% CI, –31 to 24 percentage points]; P = 0.80). In a sensitivity analysis that included dropouts, the best-case scenario yielded a difference of 5 percentage points (CI, –21 to 31 percentage points) between the groups. The secondary outcomes at weeks 22 and 52 did not differ between the groups.

Limitations: The study had a small sample and a short follow-up. A low dosage of infliximab was used, and the prednisone dosage was rapidly tapered.

Conclusions: Although too small to be definitive, the trial provides evidence that adding infliximab to prednisone for treating newly diagnosed polymyalgia rheumatica is of no benefit and may be harmful. If there is benefit, it is unlikely to be large.

Australian Clinical Trials Registry number: ACTRN012606000205538.

Editors' Notes Context Some patients with polymyalgia rheumatica have a chronic relapsing course and require long-term glucocorticoid therapy, which can lead to adverse effects. A small case series suggested that infliximab had a glucocorticoid-sparing effect. Contribution Researchers randomly assigned patients with newly diagnosed polymyalgia rheumatica to a prednisone taper plus placebo or infliximab, 3 mg/kg of body weight, at weeks 0, 2, 6, 14, and 22. They found no difference in relapse- and recurrence-free survival at 52 weeks. Caution The study was too small to definitively identify harms or small benefits. Implication Infliximab is unlikely to cause large improvements in polymyalgia rheumatica outcomes when added to a glucocorticoid taper. —The Editors

 

Author and Article Information

From the Arcispedale S. Maria Nuova, Reggio Emilia, Italy; Policlinico di Modena, Modena, Italy; Ospedale S. Chiara, Trent, Italy; Policlinico S. Salvatore, L'Aquila, Italy; Ospedale Maggiore, Parma, Italy; Università di Genova, Genoa, Italy; Università di Perugia, Perugia, Italy; Ospedale di Prato, Prato, Italy; Istituto di Ricovero e Cura a Carattere Scientifico, Fondazione Policlinico San Matteo, Pavia, Italy; and Mayo Clinic, Rochester, Minnesota.

Acknowledgment: The authors thank Giuseppe Germanò, MD, at the Arcispedale S. Maria Nuova, Reggio Emilia, Italy, for help in recruiting patients.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Carlo Salvarani, MD, Servizio di Reumatologia, Arcispedale S. Maria Nuova, Viale Risorgimento N 80, 42100 Reggio Emilia, Italy; e-mail, salvarani.carlo{at}asmn.re.it.

Current Author Addresses: Drs. Salvarani, Macchioni, Catanoso, and Boiardi: Arcispedale S. Maria Nuova, Viale Risorgimento N 80, 42100 Reggio Emilia, Italy.

Dr. Manzini: Policlinico di Modena, Via del Pozzo N 71, 41100 Modena, Italy.

Dr. Paolazzi: Ospedale S. Chiara, Largo Medaglie d'Oro N 9, 38100 Trent, Italy.

Dr. Trotta: Policlinico S. Salvatore, Via Vetoio, Coppito, 67100 L'Aquila, Italy.

Dr. Manganelli: Ospedale Maggiore, Via Gramsci N 14, 43100 Parma, Italy.

Dr. Cimmino: Ospedale S. Martino, Viale Benedetto XV N 6, 16132 Genoa, Italy.

Dr. Gerli: Policlinico Monteluce, Via Brunamonti, 06122 Perugia, Italy.

Dr. Cantini: Ospedale di Prato, Piazza Ospedale N 1, 59100 Prato, Italy.

Dr. Klersy: Policlinico S. Matteo, Piazzale Golgi 2, 27100 Pavia, Italy.

Dr. Hunder: Mayo School of Medicine, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905.

Author Contributions: Conception and design: C. Salvarani, P.L. Macchioni, M.G. Catanoso, L. Boiardi, F. Cantini, G.G. Hunder.

Analysis and interpretation of the data: C. Salvarani.

Drafting of the article: C. Salvarani.

Critical revision of the article for important intellectual content: P.L. Macchioni, M. Cimmino, L. Boiardi, G.G. Hunder.

Final approval of the article: C. Salvarani, P.L. Macchioni, C. Manzini, G. Paolazzi, A. Trotta, P. Manganelli, M. Cimmino, R. Gerli, M.G. Catanoso, L. Boiardi, F. Cantini, C. Klersy, G.G. Hunder.

Provision of study materials or patients: P.L. Macchioni, C. Manzini, G. Paolazzi, A. Trotta, P. Manganelli, M. Cimmino, R. Gerli, M.G. Catanoso.

Statistical expertise: C. Klersy.

Collection and assembly of data: C. Salvarani, P.L. Macchioni, L. Boiardi.

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