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INTRODUCTION: Although synthetic and biologic disease-modifying antirheumatic drugs are available, many patients with rheumatoid arthritis have a difficult-to-control disease and need other treatment options. Repository corticotropin injection (RCI) may alleviate symptoms and exacerbations in patients with refractory disease. METHODS: Nine patients with refractory rheumatoid arthritis were included in this study. Patients were maintained on their baseline therapies with a minimum of 7.5 mg prednisone daily. RCI was given daily at 40 U for 7 days. Patients who had an adequate disease response were given 40 U twice weekly through Week 12. For patients who had inadequate disease response, the dose was increased to 80 U daily for 7 days, followed by 80 U twice weekly through Week 12. RESULTS: The primary endpoint was >1.2 point reduction in the Disease Activity Score 28 using C-reactive protein (DAS28-CRP) at Week 12. Secondary endpoints were improvements in Health Assessment Questionnaire-Disease Index and Functional Assessment of Chronic Illness Therapy scores. Six of the nine patients met the primary endpoint. The average change in DAS28-CRP from baseline to Week 12 was numerically greater with 40 U than with 80 U RCI. Functional Assessment of Chronic Illness Therapy and Health Assessment Questionnaire-Disease Index improved as early as Week 1, and the improvements remained throughout treatment. CONCLUSION: There was no association between cortisol levels and low-dose RCI response. No serious adverse events occurred. RCI produced a clinically meaningful reduction in markers of disease activity, improved health-related quality of life, and a favorable safety profile. The response rate to RCI was substantial and shows promise in this difficult-to-treat population.
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OBJECTIVE: Applying population research to individual treatment requires understanding the connections between patient-specific characteristics, population-based studies, and treatment responses. Conducting practice-based research using individual-focused (N-of-1) trials may aid this process. We combined N-of-1 trials to compare fibromyalgia therapies and to assess the feasibility and outcomes of this approach for practice-based effectiveness research. METHODS: Community- and center-based rheumatologists enrolled patients with fibromyalgia syndrome in randomized, double-blind, multi-crossover, N-of-1 trials comparing amitriptyline and the combination amitriptyline and fluoxetine. Fibromyalgia Impact Questionnaire outcomes were used for the individuals' treatment and combined across patients for sample-based analyses. Outcomes were compared with results from more standard trial designs. RESULTS: Eight rheumatologists enrolled 58 patients in N-of-1 trials. Most physicians and patients had not previously participated in clinical trials. Using several analytic methods, the pooled results showed a better outcome score (mean difference: -6.1 +/- 2.0 to -8.0 +/- 3.7 points) in patients taking combination therapy. These population results are similar to published outcomes from a more traditional crossover trial. Neither practice type nor patient characteristics were significantly associated with the observed treatment-effect variation. Most participants, irrespective of selected treatment, felt their individual N-of-1 trials were helpful. CONCLUSION: Implementation of the combined N-of-1 methodology is feasible in rheumatology practices and results confirm greater fibromyalgia improvement with combination therapy. This research approach broadens participation, although our trials' specifics likely influenced enrollment eligibility. In addition to individual benefits, combining N-of-1 trial data provides population research benefits. This patient-focused approach should be further explored to bridge research and practice.
