Abatacept in the Treatment of Adult Dermatomyositis and Polymyositis: a Randomized, Treatment Delayed-Start Trial

Ingrid E. Lundberg¹, Anna Tjärnlund², Quan Tang³, Cecilia Wick², Maryam Dastmalchi⁴, Herman F Mann⁵, Jana Tomasová Studýnková⁵, Radka Chura⁶, Nicola J. Gullick⁷, Rosaria Salerno⁷, Eva Lindroos^3,8, Patrick Gordon⁶ and Jiri Vencovsky⁵, ¹Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden, ²Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden, ³Department of Medicine, Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden, ⁴Department of Medicine, Solna, Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden, ⁵Institute of Rheumatology, Prague, Czech Republic, ⁶Department of Rheumatology, King`s College Hospital NHS Foundation Trust, London, United Kingdom, ⁷Rheumatology, Department of Rheumatology, King`s College Hospital NHS Foundation Trust, London, United Kingdom, ⁸Department of Medicine, Rheumatology Unit, Karolinska University Hospital in Solna, Karolinska Institutet, Stockholm, Sweden., Stockholm, Sweden

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Abatacept, biopsies, Myositis, regulatory cells and treatment

Session Information

Date: Tuesday, November 10, 2015

Title: Muscle Biology, Myositis and Myopathies Poster II: Autoantibodies and Treatments in Inflammatory Myopathies

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

The aim of the study was to assess the effects of abatacept, a T cell blocking agent, on disease activity and on muscle biopsy features of adult patients with dermatomyositis (DM) or polymyositis (PM).

Methods:

Patients with DM or PM with persisting signs of active disease after treatment with glucocorticoids and ≥ one immune modulating drug for ≥ 3 months were enrolled in this randomized treatment delayed-start design trial to receive either active treatment with intravenous (10 mg/kg) infusions of abatacept or delayed start for 3 months. The primary endpoint was the number of responders, defined as improved according to the International Myositis Assessment and Clinical Studies (IMACS) Group definition of improvement (DOI), after treatment for 6 months. Secondary endpoints were the number of responders in the active treatment arm compared to the delayed onset arm at 3 months, and the efficacy after 6 months treatment on the individual components of the IMACS core set measures for the disease activity, and health-related quality of life assessed by SF-36. In 6 patients muscle biopsies were taken before and after 6 months of treatment and investigated by immunohistochemistry for inflammatory cell markers including CD3, and Foxp3 (regulatory T cells) and for cytokines. Each tissue section was evaluated coded and the degree of inflammation was evaluated by digital image analysis.

Results:

Among 20 randomized patients (9 DM, 11 PM; 13 female, 7 male), 17 were included in the analyses and 8 (47%) achieved the DOI after 6 months of active treatment. No differences between DM and PM or female and male patients were seen.

At 3 months after study start, 5 (50%) patients were responders after active treatment whereas only one (14%) patient in the delayed onset arm was defined as responder. After active treatment for 6 months (n=17), significant improvement was seen in muscle strength, assessed by the manual muscle test (MMT)-8, from (median) 70 to 73 (p=0.0082), in gastrointestinal disease activity from 3 to 0 (p=0.0156), and in muscle disease activity from 18 to 10 (p=0.0133). SF-36 physical was significantly improved from median 31 at start to 36 at end of treatment (p=0.0054). Eight adverse events were regarded as related to the drug (infections, flank pain and dizziness), of which 4 were mild and 4 were moderate. There were 3 serious AE, none of which was related to the drug. These included hospitalization due to fracture, worsening in muscle weakness and pre-existing basal cell cancer. The 6 patients with repeated muscle biopsies had a significant improvement in MMT-8 (p=0.03). There was a significant increase in positively stained area for Foxp3 whereas other markers were unchanged.

Conclusion:

In this pilot study, treatment of PM and DM patients with abatacept resulted in improved muscle performance and health-related quality of life in half of the patients. In patients with repeat muscle biopsies an increased frequency of Foxp3+ cells was recorded suggesting an effect of treatment on cells in muscle tissue.

Acknowledgement This research received funding support from Bristol-Myers Squibb.

Disclosure: I. E. Lundberg, Bristol-Myers Squibb, 2,Astra-Zeneca, 2,Novartis Pharmaceutical Corporation, 5,ATyr, 5,IDERA, 5,Servier, 5; A. Tjärnlund, None; Q. Tang, None; C. Wick, None; M. Dastmalchi, None; H. F. Mann, None; J. Tomasová Studýnková, None; R. Chura, None; N. J. Gullick, None; R. Salerno, None; E. Lindroos, None; P. Gordon, Bristol-Myers Squibb, 2; J. Vencovsky, Bristol-Myers Squibb, 2.

To cite this abstract in AMA style:

Lundberg IE, Tjärnlund A, Tang Q, Wick C, Dastmalchi M, Mann HF, Tomasová Studýnková J, Chura R, Gullick NJ, Salerno R, Lindroos E, Gordon P, Vencovsky J. Abatacept in the Treatment of Adult Dermatomyositis and Polymyositis: a Randomized, Treatment Delayed-Start Trial [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/abatacept-in-the-treatment-of-adult-dermatomyositis-and-polymyositis-a-randomized-treatment-delayed-start-trial/. Accessed .

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