Polymyalgia rheumatica is a common inflammatory disorder. The principal laboratory abnormalities are a highly elevated erythrocyte sedimentation rate (ESR) and increased serum concentrations of C-reactive protein and interleukin 6 (IL-6). Severe complications include risk of blindness, stroke and aortic arch syndrome associated with giant cell arteritis. Although corticosteroids are universally accepted as the treatment of choice, no guidelines about the optimal dosage and duration of treatment have been developed. Weyand and associates studied 27 patients with polymyalgia rheumatica to determine whether clinical or laboratory parameters could be identified that would permit stratification of patients into subsets according to differences in corticosteroid requirements.
Patients began with a regimen of 20 mg of prednisone daily as a single morning dose, which was increased by 10 mg per day before a tapering schedule was begun. The dose was then tapered by 2.5 mg every two weeks for as long as the symptoms improved. This schedule resulted in a minimal treatment duration of 18 weeks. Prednisone was increased by 5 mg per day if active disease returned. Prednisone adjustments after the third flare were decided on an individual basis. All patients were followed for a minimum of six months after discontinuation of prednisone to identify possible disease relapse.
The patients' responses to initial and subsequent therapy were assessed, as well as the total amount of corticosteroids required during follow-up. Analysis of the clinical and laboratory responses showed that the patients could be classified into three distinct subsets. Subset A included patients who had an excellent response to initial therapy and required corticosteroid treatment for less than one year; subset B included patients who had a satisfactory response to initial therapy but a long-term relapsing course that required corticosteroids for more than one year; subset C included patients who responded only partially to the initial corticosteroid dose and also required corticosteroids for longer than one year.
Pretreatment levels of pain were the lowest in subset A and the highest in subset C. On initiation of therapy, patients in these two groups demonstrated excellent improvement. Patients in subset C had initial pain reduction but, despite an increase to 30 mg of prednisone, pain levels remained elevated for the first year. Disease flares were infrequent in subset A and were a typical feature in subsets B and C.
Steroid requirements differed between subsets B and C in the early phase of the disease and continued into the second half of the first year of treatment, suggesting that disease activity during the early and chronic phases of the disease were distinct in these two patient populations. This trend did not continue over the subsequent third six-month period. Therapy was stopped in patients in subset C in a pattern similar to patients in subset B.
The clinical course was correlated with ESRs and IL-6 concentrations. The median ESR measurement before prednisone therapy was the lowest (39 mm per hour) in patients in subset A. In addition to an initially low IL-6 level, these measurements distinguished patients in subset A from all other patients. The data suggest that low ESRs and IL-6 concentrations in untreated patients correlate with a benign disease course. On initiation of therapy, patients responded with a prompt normalization of the ESR. Even in subset C, the ESR improved with a reduction of median ESR from 49 to 22 mm per hour. In contrast, production of IL-6 remained elevated in the subset C patients who were classified as partial responders.
Results indicated that pretreatment ESR levels were helpful in identifying patients who required low doses of corticosteroid therapy for less than one year. Additionally, the response pattern of IL-6 to corticosteroid therapy could identify patients with a chronic relapsing course and those for whom an initial dose of 20 mg of prednisone was not sufficient treatment.
The authors conclude that patients with polymyalgia rheumatica varied in their initial response to treatment, which predicted their course and the ability to reduce steroid intake during the chronic phase of the disease. The most unexpected finding was the high proportion of patients (26 percent) who did not respond adequately to the initial dosage of prednisone. A significant number of patients with polymyalgia rheumatica may be under-treated with an initial dosage of 20 mg per day. Pretreatment measurements of ESR and non-responsiveness of IL-6 to corticosteroid therapy are helpful in identifying patients with different treatment requirements.