Brief Report: A Prospective Open‐Label Phase IIa Trial of Tocilizumab in the Treatment of Polymyalgia Rheumatica

Abstract

Objective Interleukin-6 (IL-6) is a pivotal cytokine in the pathogenesis of polymyalgia rheumatica (PMR), yet the efficacy of IL-6 blockade with tocilizumab (TCZ) for the treatment of PMR is unknown. The aim of this study was to assess the efficacy and safety of TCZ in newly diagnosed PMR. Methods In a single-center open-label study, patients with newly diagnosed PMR who had been treated with glucocorticoids (GCs) for <1 month were treated monthly with intravenous (IV) TCZ 8 mg/kg for 1 year, with a rapid tapering of GCs according to standardized protocol. The primary end point was the proportion of patients in relapse-free remission without GC treatment at 6 months. Secondary outcome measures included duration of GC use and cumulative GC dose. Patients were followed up for 15 months. Results Ten patients were enrolled in the study. One patient withdrew after 2 months, leaving 9 patients in whom the primary end point was assessed. The primary end point of relapse-free remission without GC treatment at 6 months was achieved by all 9 of these patients. All patients who received TCZ treatment were able to discontinue GCs within 4 months of study entry. The cumulative mean ± SD prednisone dose was 1,085 ± 301 mg and the total duration of GC exposure was 3.9 ± 0.9 months. Remission persisted without relapse, in all 9 patients, throughout the entire 15-month study. Conclusion Our findings suggest that TCZ may be an effective, safe, and well-tolerated treatment for newly diagnosed patients with PMR, with a robust steroid-sparing effect.

Experience With Tocilizumab, an Interleukin 6 Inhibitor, Used for the Treatment of Giant Cell Arteritis With Severe Comorbidity

“…Вместе с тем при использовании нами короткого курса из двух инфузий ТЦЗ (суммарно 600 мг, 12,8 мг/кг) отмечен рецидив ГКА. Недавно опубли-кованы результаты открытого исследования IIA фазы у больных РПМА [26], в котором были эффективны курсы ТЦЗ со средней длительностью 3,9±0,9 мес. На фоне дан-ной терапии у всех 9 больных была достигнута ремиссия, что позволило отменить ГК примерно через 4 мес после назначения ТЦЗ.…”

Remission of Glucocorticoid-Resistant Polymyalgia Rheumatica achieved with Tocilizumab: 2 Case Reports

“…In resistant cases with elevated IL-6, there is greater occurrence of relapse and GC resistance. Elevation in plasma IL-6 and soluble IL-6 receptor levels is more sensitive for relapse than elevated acute phase reactants [16]. Female gender, advanced age and elevated ESR and CRP are risk factors for relapse/ recurrence and prolonged GC treatment [17].…”

“…TCZ, which is an IL-6 receptor monoclonal antibody, has been reported to be of benefi t to resistant PMR patients with concomitant giant cell arteritis (GCA) [16]. However, as there…”

Management of polymyalgia rheumatica in older people

“…53 The rationale for its use in PMR stems from the central role that IL‐6 is thought to play in PMR pathogenesis, as well as the successful use of tocilizumab in giant cell arteritis . The efficacy of tocilizumab for controlling symptoms and providing a steroid‐sparing effect in newly diagnosed PMR has been demonstrated in two open‐label trials, with Phase 3 trials now underway…”