Abatacept for the Treatment of Myositis-associated Interstitial Lung Disease

Summary

A randomized, controlled pilot trial to evaluate the efficacy and safety of subcutaneous Abatacept in treating interstitial lung disease associated with the anti-synthetase syndrome.

Timeline

Start

2018-01-01

Primary completion

2022-05-30

Completion

2023-07-30

Publications

• Background Kurasawa K, Nawata Y, Takabayashi K, Kumano K, Kita Y, Takiguchi Y, Kuriyama T, Sueishi M, Saito Y, Iwamoto I. Activation of pulmonary T cells in corticosteroid-resistant and -sensitive interstitial pneumonitis in dermatomyositis/polymyositis. Clin Exp Immunol. 2002 Sep;129(3):541-8. doi: 10.1046/j.1365-2249.2002.01933.x.
• Background Israel-Assayag E, Fournier M, Cormier Y. Blockade of T cell costimulation by CTLA4-Ig inhibits lung inflammation in murine hypersensitivity pneumonitis. J Immunol. 1999 Dec 15;163(12):6794-9.
• Background Jimenez-Alvarez L, Arreola JL, Ramirez-Martinez G, Ortiz-Quintero B, Gaxiola M, Reynoso-Robles R, Avila-Moreno F, Urrea F, Pardo A, Selman M, Zuniga J. The effect of CTLA-4Ig, a CD28/B7 antagonist, on the lung inflammation and T cell subset profile during murine hypersensitivity pneumonitis. Exp Mol Pathol. 2011 Dec;91(3):718-22. doi: 10.1016/j.yexmp.2011.09.010. Epub 2011 Sep 14.
• Background Murata K, Dalakas MC. Expression of the costimulatory molecule BB-1, the ligands CTLA-4 and CD28, and their mRNA in inflammatory myopathies. Am J Pathol. 1999 Aug;155(2):453-60. doi: 10.1016/s0002-9440(10)65141-3.
• Background Nagaraju K, Raben N, Villalba ML, Danning C, Loeffler LA, Lee E, Tresser N, Abati A, Fetsch P, Plotz PH. Costimulatory markers in muscle of patients with idiopathic inflammatory myopathies and in cultured muscle cells. Clin Immunol. 1999 Aug;92(2):161-9. doi: 10.1006/clim.1999.4743.
• Background Cutolo M, Soldano S, Montagna P, Sulli A, Seriolo B, Villaggio B, Triolo P, Clerico P, Felli L, Brizzolara R. CTLA4-Ig interacts with cultured synovial macrophages from rheumatoid arthritis patients and downregulates cytokine production. Arthritis Res Ther. 2009;11(6):R176. doi: 10.1186/ar2865. Epub 2009 Nov 23.
• Background Buch MH, Boyle DL, Rosengren S, Saleem B, Reece RJ, Rhodes LA, Radjenovic A, English A, Tang H, Vratsanos G, O'Connor P, Firestein GS, Emery P. Mode of action of abatacept in rheumatoid arthritis patients having failed tumour necrosis factor blockade: a histological, gene expression and dynamic magnetic resonance imaging pilot study. Ann Rheum Dis. 2009 Jul;68(7):1220-7. doi: 10.1136/ard.2008.091876. Epub 2008 Sep 4.
• Background Lumsden JM, Roberts JM, Harris NL, Peach RJ, Ronchese F. Differential requirement for CD80 and CD80/CD86-dependent costimulation in the lung immune response to an influenza virus infection. J Immunol. 2000 Jan 1;164(1):79-85. doi: 10.4049/jimmunol.164.1.79.
• Background Platt AM, Gibson VB, Patakas A, Benson RA, Nadler SG, Brewer JM, McInnes IB, Garside P. Abatacept limits breach of self-tolerance in a murine model of arthritis via effects on the generation of T follicular helper cells. J Immunol. 2010 Aug 1;185(3):1558-67. doi: 10.4049/jimmunol.1001311. Epub 2010 Jul 2.
• Background Mitsui T, Kuroda Y, Ueno S, Kaji R. The effects of FK506 on refractory inflammatory myopathies. Acta Neurol Belg. 2011 Sep;111(3):188-94.
• Background Ochi S, Nanki T, Takada K, Suzuki F, Komano Y, Kubota T, Miyasaka N. Favorable outcomes with tacrolimus in two patients with refractory interstitial lung disease associated with polymyositis/dermatomyositis. Clin Exp Rheumatol. 2005 Sep-Oct;23(5):707-10.
• Background Ando M, Miyazaki E, Yamasue M, Sadamura Y, Ishii T, Takenaka R, Ito T, Nureki S, Kumamoto T. Successful treatment with tacrolimus of progressive interstitial pneumonia associated with amyopathic dermatomyositis refractory to cyclosporine. Clin Rheumatol. 2010 Apr;29(4):443-5. doi: 10.1007/s10067-009-1358-x. Epub 2010 Feb 4.
• Background Takada K, Nagasaka K, Miyasaka N. Polymyositis/dermatomyositis and interstitial lung disease: a new therapeutic approach with T-cell-specific immunosuppressants. Autoimmunity. 2005 Aug;38(5):383-92. doi: 10.1080/08916930500124023.
• Background Wilkes MR, Sereika SM, Fertig N, Lucas MR, Oddis CV. Treatment of antisynthetase-associated interstitial lung disease with tacrolimus. Arthritis Rheum. 2005 Aug;52(8):2439-46. doi: 10.1002/art.21240.
• Background Guglielmo S, Bertinaria M, Rolando B, Crosetti M, Fruttero R, Yardley V, Croft SL, Gasco A. A new series of amodiaquine analogues modified in the basic side chain with in vitro antileishmanial and antiplasmodial activity. Eur J Med Chem. 2009 Dec;44(12):5071-9. doi: 10.1016/j.ejmech.2009.09.012. Epub 2009 Sep 15.
• Background Kerola AM, Nieminen TV, Kauppi MJ, Kautiainen H, Puolakka K, Virta LJ, Kerola T. Increased risk of levothyroxine-treated hypothyroidism preceding the diagnosis of rheumatoid arthritis: a nationwide registry study. Clin Exp Rheumatol. 2014 Jul-Aug;32(4):455-9. Epub 2014 Jun 6.
• Background Arabshahi B, Silverman RA, Jones OY, Rider LG. Abatacept and sodium thiosulfate for treatment of recalcitrant juvenile dermatomyositis complicated by ulceration and calcinosis. J Pediatr. 2012 Mar;160(3):520-2. doi: 10.1016/j.jpeds.2011.11.057. Epub 2012 Jan 13.
• Background Maeshima K, Kiyonaga Y, Imada C, Iwakura M, Hamasaki H, Haranaka M, Ishii K. Successful treatment of refractory anti-signal recognition particle myopathy using abatacept. Rheumatology (Oxford). 2014 Feb;53(2):379-80. doi: 10.1093/rheumatology/ket251. Epub 2013 Aug 6. No abstract available.
• Background Elhai M, Meunier M, Matucci-Cerinic M, Maurer B, Riemekasten G, Leturcq T, Pellerito R, Von Muhlen CA, Vacca A, Airo P, Bartoli F, Fiori G, Bokarewa M, Riccieri V, Becker M, Avouac J, Muller-Ladner U, Distler O, Allanore Y; EUSTAR (EULAR Scleroderma Trials and Research group). Outcomes of patients with systemic sclerosis-associated polyarthritis and myopathy treated with tocilizumab or abatacept: a EUSTAR observational study. Ann Rheum Dis. 2013 Jul;72(7):1217-20. doi: 10.1136/annrheumdis-2012-202657. Epub 2012 Dec 19.
• Background Mera-Varela A, Perez-Pampin E. Abatacept therapy in rheumatoid arthritis with interstitial lung disease. J Clin Rheumatol. 2014 Dec;20(8):445-6. doi: 10.1097/RHU.0000000000000084. No abstract available.
• Background Khanna D, Mittoo S, Aggarwal R, Proudman SM, Dalbeth N, Matteson EL, Brown K, Flaherty K, Wells AU, Seibold JR, Strand V. Connective Tissue Disease-associated Interstitial Lung Diseases (CTD-ILD) - Report from OMERACT CTD-ILD Working Group. J Rheumatol. 2015 Nov;42(11):2168-71. doi: 10.3899/jrheum.141182. Epub 2015 Mar 1.
• Aggarwal R, Pongtarakulpanit N, Sullivan DI, Moghadam-Kia S, Bae SS, Wilkerson J, Saygin D, Marder G, Venuturupalli S, Dellaripa PF, Danoff SK, Doyle T, Hunninghake GM, Lee JS, Fischer A, Falk J, Johnson C, Koontz D, Ascherman DP, Oddis CV. Abatacept for the treatment of myositis-associated interstitial lung disease. Rheumatology (Oxford). 2025 Dec 1;64(SI):SI156-SI168. doi: 10.1093/rheumatology/keaf218.
• Bae SS, Abtin F, Kim G, Markovic D, Chan C, Moghadam-Kia S, Oddis CV, Sullivan D, Marder G, Venuturupalli S, Dellaripa PF, Doyle TJ, Hunninghake GM, Falk J, Charles-Schoeman C, Tashkin DP, Goldin J, Aggarwal R. Relationship between high-resolution computed tomography quantitative imaging analysis and physiological and clinical features in antisynthetase syndrome-related interstitial lung disease. RMD Open. 2024 Nov 27;10(4):e004592. doi: 10.1136/rmdopen-2024-004592.
• Bae SS, Markovic D, Saygin D, Sullivan D, Yamaguchi K, Moghadam-Kia S, Oddis CV, Abtin F, Kim GHJ, Marder G, Venuturupalli S, Dellaripa PF, Danoff S, Doyle T, Hunninghake G, Lee JS, Falk J, Johnson C, Goldin J, Tashkin D, Charles-Schoeman C, Aggarwal R. Associations between 6-minute walk distance and physiologic measures and clinical outcomes in myositis-associated interstitial lung disease. Rheumatology (Oxford). 2025 Dec 1;64(SI):SI79-SI87. doi: 10.1093/rheumatology/keae477.

Drugs

Indications