Background Treatment with glucocorticoid (GC) is the preferred therapy for polymyalgia rheumatica (PMR), but half of the PMR patients experience a flare-up(s) of disease activity upon GC tapering or discontinuation. In addition, some patients show poor responses to the starting GC regimen.
Objectives We intended to compare clinical characteristics and therapeutic outcomes between GC responders and GC-resistant patients and to examine the effectiveness of tocilizumab (TCZ) on the GC-resistant PMR.
Methods We reviewed medical records of all patients who had been diagnosed as having PMR at our hospital between October 2007 and February 2013. All patients started with an initial dosage of 15 mg/day of prednisolone for 2-3 weeks, followed by reduction of the daily dose by 2.5 mg every 2 weeks till 10 mg/day, then by 1-2 mg every month till reaching the minimal maintenance dosage of 5 mg/day, as long as symptoms remained improved or remission persisted. The GC responders were defined as patients who had responded well to the initial GC regimen, tolerated reduction to the minimal maintenance dose, and thereafter controlled disease activity with 5 mg/day or less of prednisolone for at least 6 months. Remission was defined as achieving PMR activity score (PMR-AS) of 0-1.5. The flare-up was defined as an exacerbation or a reappearance of PMR symptoms associated with abnormal C-reactive protein levels (>0.5 mg/dl), erythrocyte sedimentation rates (>30 mm/hour), or both. PMR-AS was calculated according to the equation proposed by Leeb and Bird.
Results We identified 14 GC responders and 9 GC-resistant patients. All of these patients fulfilled the 2012 ACR/EULAR classification criteria for PMR. The GC responders achieved remission within 2-6 weeks. Among these patients, 7 maintained remission without prednisolone for more than 6 months. For the GC-resistant patients, the additional use of methotrexate (MTX, 5 cases), salazosulfapyridine (SSZ, 1 case), and TCZ (3 cases) was effective, though 13-39 weeks were required for achievement of remission. Baseline values of PMR-AS and its components, especially the ability to elevate the upper limbs (EUL), were significantly higher in the GC-resistant patients compared with the GC responders. We present 3 patients with GC-resistant PMR who received TCZ therapy. In case 1, a 55-year-old woman failed to control disease activity by treatment with prednisolone and additional MTX, but the use of TCZ produced remission. In case 2, a 67-year-old woman achieved remission by treatment with prednisolone and additional SSZ, but after 3 months of maintenance GC therapy, she experienced a flare. The addition of TCZ rapidly improved her PMR symptoms. Case 3 was TCZ-refractory PMR. Despite a 6-month TCZ therapy, a 73-year-old woman failed to achieve remission. However, the addition of MTX produced remission.
Conclusions The PMR-AS value at baseline may be helpful in dividing PMR patients into 2 groups with different treatment requirements. Alternative immunosuppressive agents should be considered for the GC-resistant PMR patients, which can decrease the cumulative GC exposure. Large controlled studies are required to develop guidelines for the optimal use of TCZ in GC-resistant PMR.
Leeb BF, Bird HA. Ann Rheum Dis 2004; 63: 1279-83.
Disclosure of Interest S. Mori Grant/research support: Chugai Pharmaceutical Co. Ltd. and Pfizer Japan Ltd., Y. Koga: None declared