Background/Purpose: Polymyalgia rheumatica (PMR) is a common condition of unknown etiology with a lifetime risk of 2.43% in women and 1.66% in men.¹ PMR is characterized by pain and stiffness in the neck, shoulders and/or pelvic girdle, and is more severe in the morning with a duration >1 hour in most patients. It is generally agreed that the absence of a prompt response to a moderate glucocorticoid (GC) dose (15 mg prednisone daily) indicates a diagnosis other than PMR.² This higher dose of a GC is associated with more adverse drug effects than lower doses.³ Blood concentrations of interleukin (IL) -6 increase during the night and peak in the early morning hours in parallel with PMR patients’ pain and stiffness.⁴ A timed (delayed) release prednisone preparation (DR GC) was developed to target treatment to the nighttime increase in IL-6.⁵ It has been shown that this formulation provides better control of rheumatoid arthritis symptoms than the same dose of conventional immediate release prednisone (IR GC) taken in the morning and possibly permit a lower initial dose.⁶

Methods: In this preliminary 4-week, randomized, controlled, open-label two period trial, conducted in collaboration with OMERACT, patients with PMR responsive to GC received one of 3 nighttime doses of DR GC (4 mg, 7 mg or 10 mg) for 2 weeks followed by treatment with 15 mg IR GC in the morning for 2 weeks. The primary outcome was the change from baseline in the severity of morning stiffness (measured on a 10-point visual analog scale [VAS]) with DR GC vs that with IR GC with each patient as their own control. Pain was also evaluated using a 10-point VAS.

Results:

A total of 8 patients were enrolled (n=3 for 4 mg DR GC, 1 for 7 mg DR GC, 4 for 10 mg DR GC) and all completed the trial. The mean baseline value for morning stiffness was 5.2, and changes from baseline with 4, 7 and 10 mg DR GC were -4.5, -1.0, and -3.1, respectively. Those for 15 mg IR GC in the patients who received 4, 7, or 10 mg DR GC during the first treatment period were -4.2, -2.5, and -3.9. The mean baseline pain score was 5.2 and the reductions from baseline with 4, 7, and 10 mg DR GC were -4.4, -0.8, and -2.7, respectively. Those for 15 mg IR GC in the patients who received 4, 7, or 10 mg DR GC during the first treatment period were -4.3, -2.0, and -3.6. Two patients treated with 10 mg DR GC experienced mild adverse events (1 mild skin tear and 1 decrease in vitamin D). No adverse events were reported during treatment with 15 mg IR GC.

Conclusion: Results of this small-scale study indicated that a low-dose DR GC has effects on PMR-associated pain and stiffness similar to those of 15 mg IR GC. The efficacy of low-dose DR GC may improve the long-term safety of PMR treatment. These data warrant consideration for initiation of a larger study evaluating the efficacy and safety of DR GC in this patient population.

1. Crowson CS, et al. Arthritis Rheum 2011;63:633-9.
2. Unwin B, et al. Am Fam Physician 2006;74:1547-1554.
3. DaSilva JAP, et al. Ann Rheum Dis 2006;65(3):285-293.
4. Zakout S, et al. Ann Rheum Dis 2012;71(Suppl 3):643.
5. RAYOS (prednisone) delayed-release tablets. Horizon Pharma. http://www.rayosrx.com/hcp/pharma-dosing.php
6. Buttgereit F, et al. Lancet 2008;371:205-214.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-randomized-open-label-dose-ranging-study-of-oral-delayed-release-prednisone-in-patients-with-untreated-polymyalgia-rheumatica/