Rapamycin Vs. Placebo for the Treatment of Inclusion Body Myositis: Improvement of the 6 Min Walking Distance, a Functional Scale, the FVC and Muscle Quantitative MRI

Olivier Benveniste¹, Jean-Yves Hogrel², Melanie Annoussamy², Damien Bachasson², Aude Rigolet³, Laurent Servais², Joe-Elie Salem⁴, Baptiste Hervier³, Oceane Landon Cardinal⁵, Kuberaka Mariampillai¹, Jean-Sebastien hulot⁴, Pierre Carlier² and Yves Allenbach⁶, ¹Assistance Publique - Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Internal Medicine and Clinical Immunology, Hospital University Department: inflammation, immunopathology and biotherapy (DHU i2B), Paris, France, Paris, France, ²Institute of Myology, Paris, France, ³Internal Medicine, Pitié-Salpêtrière University Hospital, Paris, France, ⁴INSERM, CIC-1421, Paris, France, ⁵Internal Medicine, Assistance Public - Hopitaux de Paris, Pitié-Salpêtrire University Hospital, Paris, France, ⁶Internal Medicine, Assistance Public - Hopitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: October 19, 2017

Keywords: Late-Breaking 2017, Myositis

Session Information

Date: Tuesday, November 7, 2017

Title: ACR Late-Breaking Abstract Session

Session Type: ACR Late-breaking Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose:

Inclusion body Myositis (IBM) is the most frequent myositis in patients over 50 years old. Conventional immunosuppressive drugs are today ineffective or even aggravate muscle deficits. Rapamycin is a mTOR inhibitor used in organ transplantation. Potentially, rapamycin can deplete T effector cells, preserve T regulatory cells and induce autophagy (protein degradation), all parameters impaired during IBM.

Methods:

RAPAMI is a prospective, randomized, controlled, double blind, monocentric, phase IIb trial evaluating the efficacy of rapamycin against placebo (NCT02481453). The primary endpoint was stabilization of maximal voluntary quadriceps isometric strength assessed with a dynamometer (Biodex System3 pro). Secondary endpoints included safety, other muscle groups strength, distance walked in 6 minutes (6MWD), pulmonary functional tests, functional scales, and muscle quality assessed by quantitative nuclear resonance magnetic exams (NRM).

Results:

Forty-four patients were treated by oral rapamycin (2 mg/d, n=22) or placebo (n=22) during 12 months (M12). Twelve months after the initiation of the treatment, the quadriceps strength decreased significantly and similarly in both groups (mean relative change: -11.07% vs. -12.36 %). Nevertheless, in comparison to the placebo group, 6MWD was unchanged (mean change: -4.1 m vs. -38.5 m, p=0.035), IBM weakness composite index was less degraded (11.91% vs. 24.26%, p=0.038) and forced vital capacity significantly improved (mean relative change: +12.3% vs. 1.6%, p=0.016). Additionally, NRM showed significant less fat muscle replacement (difference between M12 and baseline in %) in quadriceps (1.7 vs. 4.4, p=0.025) or hamstrings (0.9 vs. 7.3, p=0.027). Finally in NRM, the loss between M12 and baseline of contractile cross-sectional area (mm²) was less pronounced in quadriceps (-3.7 vs. -10.7, p=0.005).

Conclusion: Even if the primary endpoint was not reached, these first results showed coherent data in favor of rapamycin. Notably for the first time in a RCT, an improvement of the 6MWD is observed during IBM.

Disclosure: O. Benveniste, None; J. Y. Hogrel, None; M. Annoussamy, None; D. Bachasson, None; A. Rigolet, None; L. Servais, None; J. E. Salem, None; B. Hervier, None; O. Landon Cardinal, None; K. Mariampillai, None; J. S. hulot, None; P. Carlier, None; Y. Allenbach, None.

To cite this abstract in AMA style:

Benveniste O, Hogrel JY, Annoussamy M, Bachasson D, Rigolet A, Servais L, Salem JE, Hervier B, Landon Cardinal O, Mariampillai K, hulot JS, Carlier P, Allenbach Y. Rapamycin Vs. Placebo for the Treatment of Inclusion Body Myositis: Improvement of the 6 Min Walking Distance, a Functional Scale, the FVC and Muscle Quantitative MRI [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/rapamycin-vs-placebo-for-the-treatment-of-inclusion-body-myositis-improvement-of-the-6-min-walking-distance-a-functional-scale-the-fvc-and-muscle-quantitative-mri/. Accessed .

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