https://doi.org/10.4081/reumatismo.2025.1718
Small molecules in idiopathic inflammatory myopathies: a systematic review and a multicenter case series about Janus kinase inhibitors and apremilast
Submitted: 26 February 2024
Accepted: 6 August 2024
Published: 13 January 2025
Accepted: 6 August 2024
Abstract Views: 119
PDF: 43
SUPPLEMENTARY MATERIAL: 5
SUPPLEMENTARY MATERIAL: 5
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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Objective. Idiopathic inflammatory myopathies (IIM) are rare autoimmune diseases that primarily affect striated muscles; skin, joints, and lungs may be involved with different degrees of severity. Traditional treatment relies on high-dose glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs.
Methods. A growing amount of evidence is demonstrating the potential role of novel treatments in the management of IIM. We report our experience with Janus kinase inhibitors (JAKi) in these conditions and review the current evidence for the use of small molecules in real-life clinical practice.
Results. A total of 41 papers were retrieved from PubMed, 37 papers concerning IIM and JAKi, and 4 papers concerning IIM and apremilast.
Conclusions. An overall good efficacy was evidenced in IIM-associated skin lesions, including rash, ulcers, and calcinosis. If present, muscle and joint involvement demonstrated a good response to therapy, while it was not possible to draw any conclusion about dysphagia. No life-threatening adverse events were reported.
Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, Visser M de, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis 2017; 76: 1955-64.
DOI: https://doi.org/10.1136/annrheumdis-2017-212786
Pipitone N, Salvarani C. Treatment of inflammatory myopathies. Expert Rev Clin Immunol 2018; 14: 607-21.
DOI: https://doi.org/10.1080/1744666X.2018.1491307
Pipitone N, Salvarani C. Up-to-date treatment and management of myositis. Curr Opin Rheumatol 2020; 32: 523-7.
DOI: https://doi.org/10.1097/BOR.0000000000000745
Chiapparoli I, Galluzzo C, Salvarani C, Pipitone N. A glance into the future of myositis therapy. Ther Adv Musculoskelet Dis 2022; 14: 1759720X2211002.
DOI: https://doi.org/10.1177/1759720X221100299
Grazzini S, Rizzo C, Conticini E, D’Alessandro R, La Barbera L, D’Alessandro M, et al. The role of bDMARDs in idiopathic inflammatory myopathies: a systematic literature review. Autoimmun Rev 2023; 22: 103264.
DOI: https://doi.org/10.1016/j.autrev.2022.103264
Conticini E, Falsetti P, Al Khayyat SG, Baldi C, Bellisai F, Bardelli M, et al. A novel grey scale and Power Doppler ultrasonographic score for idiopathic inflammatory myopathies: Siena Myositis Ultrasound Grading Scale. Rheumatology 2021; 61: 185-94.
DOI: https://doi.org/10.1093/rheumatology/keab340
You H, Xu D, Zhao J, Li J, Wang Q, Tian X, et al. JAK inhibitors: prospects in connective tissue diseases. Clin Rev Allergy Immunol 2020; 59: 334-51.
DOI: https://doi.org/10.1007/s12016-020-08786-6
Moghadam-Kia S, Charlton D, Aggarwal R, Oddis C V. Management of refractory cutaneous dermatomyositis: potential role of Janus kinase inhibition with tofacitinib. Rheumatology 2019; 58: 1011-5.
DOI: https://doi.org/10.1093/rheumatology/key366
Ll Wilkinson MG, Deakin CT, Papadopoulou C, Eleftheriou D, Wedderburn LR. JAK inhibitors: a potential treatment for JDM in the context of the role of interferon-driven pathology. Pediatr Rheumatol Online J 2021; 19: 146.
DOI: https://doi.org/10.1186/s12969-021-00637-8
Paik JJ, Christopher-Stine L. A case of refractory dermatomyositis responsive to tofacitinib. Semin Arthritis Rheum 2017; 46: e19.
DOI: https://doi.org/10.1016/j.semarthrit.2016.08.009
Hornig J, Weinhage T, Schmidt LH, Buerke B, Schneider U, Pavenstädt H, et al. Response of dermatomyositis with lung involvement to Janus kinase inhibitor treatment. Z Rheumatol 2018; 77: 952-7. [Article in German].
DOI: https://doi.org/10.1007/s00393-018-0565-8
Kurtzman DJB, Wright NA, Lin J, Femia AN, Merola JF, Patel M, et al. Tofacitinib citrate for refractory cutaneous dermatomyositis: an alternative treatment. JAMA Dermatol 2016; 152: 944-5.
DOI: https://doi.org/10.1001/jamadermatol.2016.0866
Wendel S, Venhoff N, Frye BC, May AM, Agarwal P, Rizzi M, et al. Successful treatment of extensive calcifications and acute pulmonary involvement in dermatomyositis with the Janus-Kinase inhibitor tofacitinib – a report of two cases. J Autoimmun 2019; 100: 131-6.
DOI: https://doi.org/10.1016/j.jaut.2019.03.003
Ishikawa Y, Kasuya T, Fujiwara M, Kita Y. Tofacitinib for recurrence of antimelanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis after remission: a case report. Medicine 2020; 99: e21943.
DOI: https://doi.org/10.1097/MD.0000000000021943
Ohmura S, Yamabe T, Naniwa T. Successful dose escalation of tofacitinib for refractory dermatomyositis and interstitial lung disease with anti-melanoma differentiation-associated gene 5 antibodies. Mod Rheumatol Case Rep 2021; 5: 76-81.
DOI: https://doi.org/10.1080/24725625.2020.1816674
Navarro-Navarro I, Jiménez-Gallo D, Rodríguez-Mateos ME, Rodríguez-Hernández C, Linares-Barrios M. Treatment of refractory anti-NXP2 and anti-TIF1γ dermatomyositis with tofacitinib. J Dtsch Dermatol Ges 2021; 19: 443-7.
DOI: https://doi.org/10.1111/ddg.14276_g
Crespo Cruz A, del Boz J, Romero Gómez C. Good response to tofacitinib in refractory amyopathic dermatomyositis. Actas Dermosifiliogr 2021; 112: 374-6.
DOI: https://doi.org/10.1016/j.adengl.2021.01.034
Hosokawa Y, Oiwa H. A case of refractory interstitial lung disease in anti-MDA5-positive dermatomyositis that improved after switching to tofacitinib. J Clin Rheumatol 2021; 27: S661-2.
DOI: https://doi.org/10.1097/RHU.0000000000001645
Shneyderman M, Ahlawat S, Christopher-Stine L, Paik JJ. Calcinosis in refractory dermatomyositis improves with tofacitinib monotherapy: a case series. Rheumatology 2021; 60: e387-8.
DOI: https://doi.org/10.1093/rheumatology/keab421
Paik JJ, Casciola-Rosen L, Shin JY, Albayda J, Tiniakou E, Leung DG, et al. Study of tofacitinib in refractory dermatomyositis: an open-label pilot study of ten patients. Arthritis Rheumatol 2021; 73: 858-65.
DOI: https://doi.org/10.1002/art.41602
Paik JJ, Shneyderman M, Gutierrez-Alamillo L, Albayda J, Tiniakou E, Perin J, et al. Long-term extension study of tofacitinib in refractory dermatomyositis. Arthritis Rheumatol 2022; 74: 371-2.
DOI: https://doi.org/10.1002/art.41944
Robert M, Gallay L, Garnier L, Pescarmona R, Hot A. Contribution of the interferon score in the management of an anti-NXP2 dermatomyositis patient with calcinosis successfully treated with tofacitinib. Joint Bone Spine 2023; 90: 105532.
DOI: https://doi.org/10.1016/j.jbspin.2023.105532
Luo M, Chen L, He H, He F. Treatment of MDA5-positive dermatomyositis complicated by gangrenous cholecystitis with tofacitinib. Eur J Med Res 2022; 27: 68.
DOI: https://doi.org/10.1186/s40001-022-00693-0
Castillo R, Albayda J. Refractory alopecia universalis associated with dermatomyositis successfully treated with tofacitinib. Mod Rheumatol Case Rep 2022; 6: 199-202.
DOI: https://doi.org/10.1093/mrcr/rxac012
Plante J, Eason C, Santa Lucia G, Robinson I, Elston D. A retrospective review of tofacitinib in the treatment of refractory dermatomyositis. J Drugs Dermatol 2022; 21: 1133-4.
Min MS, Alsarheed A, Kassamali B, Mazori DR, Schaefer M, Merola JF, et al. Tofacitinib as treatment for refractory dermatomyositis: a retrospective study from 2 academic medical centers. J Am Acad Dermatol 2022; 86: 423-5.
DOI: https://doi.org/10.1016/j.jaad.2021.07.003
Wang Y, Luo J, Lv X, Li Y, An Q, Mo L, et al. Tofacitinib for new-onset adult patients with anti-melanoma differentiation-associated 5 gene antibody positive dermatomyositis. Clin Rheumatol 2023; 42: 1847-53.
DOI: https://doi.org/10.1007/s10067-023-06567-y
Pineton De Chambrun M, Hervier B, Chauveau S, Tandjaoui-Lambiotte Y, Combes A, Uzunhan Y. Tofacitinib in antisynthetase syndrome-related rapidly progressive interstitial lung disease. Rheumatology 2020; 59: e142-3.
DOI: https://doi.org/10.1093/rheumatology/keaa323
Conca W, Weheba I, Abouzied ME, Abdelsayed A, Aleyouni Y, Al‐Mutairy E, et al. Iacta Alea Est: the inexorable advance of tofacitinib in the treatment of dermatomyositis-associated rapidly progressive interstitial lung disease. A case report. Front Pharmacol 2020; 11: 585761.
DOI: https://doi.org/10.3389/fphar.2020.585761
Tseng C-W. Tofacitinib treatment in anti-glycyl-tRNA synthetase antibody interstitial lung disease – a case report. Int J Rheum Dis 2023; 26: 781-5.
DOI: https://doi.org/10.1111/1756-185X.14516
Babaoglu H, Varan O, Atas N, Satis H, Salman R, Tufan A. Tofacitinib for the treatment of refractory polymyositis. J Clin Rheumatol 2019; 25: e141-2.
DOI: https://doi.org/10.1097/RHU.0000000000000807
Takanashi S, Kaneko Y, Takeuchi T. Tofacitinib in interstitial lung disease complicated with anti-MDA5 antibody-positive dermatomyositis: a literature review. Mod Rheumatol 2021; 32: 231-7.
DOI: https://doi.org/10.1080/14397595.2021.1906505
Shirai T, Machiyama T, Sato H, Ishii T, Fujii H. Intensive induction therapy combining tofacitinib, rituximab and plasma exchange in severe anti-melanoma differentiation-associatedprotein-5 antibody-positive dermatomyositis. Clin Exp Rheumatol 2023; 41: 291-300.
DOI: https://doi.org/10.55563/clinexprheumatol/8kulbf
Ida T, Furuta S, Takayama A, Tamura J, Hayashi Y, Abe K, et al. Efficacy and safety of dose escalation of tofacitinib in refractory anti-MDA5 antibody-positive dermatomyositis. RMD Open 2023; 9: e002795.
DOI: https://doi.org/10.1136/rmdopen-2022-002795
Hiraoka D, Ishizaki J, Horie K, Matsumoto T, Suemori K, Takenaka K, et al. A case of clinically amyopathic dermatomyositis that was refractory to intensive immunosuppressive therapy including tofacitinib, but successfully treated with plasma exchange therapy. Mod Rheumatol Case Rep 2022; 6: 194-8.
DOI: https://doi.org/10.1093/mrcr/rxab054
Fan L, Lyu W, Liu H, Jiang H, Chen L, Liu Y, et al. A retrospective analysis of outcome in melanoma differentiation–associated gene 5–related interstitial lung disease treated with tofacitinib or tacrolimus. J Rheumatol 2022; 49: 1356-64.
DOI: https://doi.org/10.3899/jrheum.220367
Delvino P, Bartoletti A, Monti S, Biglia A, Montecucco C, Carducci M, et al. Successful treatment with baricitinib in a patient with refractory cutaneous dermatomyositis. Rheumatology 2020; 59: e125-7.
DOI: https://doi.org/10.1093/rheumatology/keaa184
Chen D, Huang W, Zhongjie W, Feifeng R, Luo L, Jun Z, et al. Good efficacy achieved by baricitinib in the treatment of anti-MDA5 antibody-positive dermatomyositis with alopecia areata. Rheumatology 2022;61: e221-3.
DOI: https://doi.org/10.1093/rheumatology/keac084
Fischer K, Aringer M, Steininger J, Heil J, Beissert S, Abraham S, et al. Improvement of cutaneous inflammation and panniculitis in patients with dermatomyositis by the Janus kinase inhibitor baricitinib. Br J Dermatol 2022; 187: 432-5.
DOI: https://doi.org/10.1111/bjd.21252
Landon-Cardinal O, Guillaume-Jugnot P, Toquet S, Sbeih N, Rigolet A, Champtiaux N, et al. JAK inhibitors for the treatment of adult dermatomyositis: a pilot study. J Am Acad Dermatol 2023; 88: 924-6.
DOI: https://doi.org/10.1016/j.jaad.2022.10.055
Zhao Q, Zhu Z, Fu Q, Shih Y, Wu D, Chen L, et al. Baricitinib for the treatment of cutaneous dermatomyositis: a prospective, open-label study. J Am Acad Dermatol 2022; 87: 1374-6.
DOI: https://doi.org/10.1016/j.jaad.2022.08.025
Hornung T, Janzen V, Heidgen F-J, Wolf D, Bieber T, Wenzel J. Remission of recalcitrant dermatomyositis treated with ruxolitinib. N Engl J Med 2014; 371: 2537-8.
DOI: https://doi.org/10.1056/NEJMc1412997
Ladislau L, Suárez-Calvet X, Toquet S, Landon-Cardinal O, Amelin D, Depp M, et al. JAK inhibitor improves type i interferon induced damage: proof of concept in dermatomyositis. Brain 2018; 141: 1609-21.
DOI: https://doi.org/10.1093/brain/awy105
Jalles C, Deroux A, Tardieu M, Lugosi M, Viel S, Benveniste O, et al. Severe MDA5 dermatomyositis associated with cancer and controlled by JAK inhibitor. Rev Med Interne 2020; 41: 421-4.
DOI: https://doi.org/10.1016/j.revmed.2020.02.015
Fetter T, Cuevas Rios G, Niebel D, Bieber T, Wenzel J. Unexpected hair regrowth in a patient with longstanding alopecia universalis during treatment of recalcitrant dermatomyositis with the janus kinase inhibitor ruxolitinib. Acta Derm Venereol 2020; 100: adv00144.
DOI: https://doi.org/10.2340/00015555-3481
Paul C, Cather J, Gooderham M, Poulin Y, Mrowietz U, Ferrandiz C, et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2). Br J Dermatol 2015; 173: 1387-99.
DOI: https://doi.org/10.1111/bjd.14164
Edwards CJ, Blanco FJ, Crowley J, Birbara CA, Jaworski J, Aelion J, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis 2016; 75: 1065-73.
DOI: https://doi.org/10.1136/annrheumdis-2015-207963
Keating GM. Apremilast: a review in psoriasis and psoriatic arthritis. Drugs 2017; 77: 459-72.
DOI: https://doi.org/10.1007/s40265-017-0709-1
Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol 2012; 83: 1583-90.
DOI: https://doi.org/10.1016/j.bcp.2012.01.001
Notarnicola A, Lapadula G, Natuzzi D, Lundberg IE, Iannone F. Correlation between serum levels of IL-15 and IL-17 in patients with idiopathic inflammatory myopathies. Scand J Rheumatol 2015; 44: 224-8.
DOI: https://doi.org/10.3109/03009742.2014.956141
Hassan AB, Fathi M, Dastmalchi M, Lundberg IE, Padyukov L. Genetically determined imbalance between serum levels of tumour necrosis factor (TNF) and interleukin (IL)-10 is associated with anti-Jo-1 and anti-Ro52 autoantibodies in patients with poly- and dermatomyositis. J Autoimmun 2006; 27: 62-8.
DOI: https://doi.org/10.1016/j.jaut.2006.06.003
Cerezo LA, Vencovský J, Šenolt L. Cytokines and inflammatory mediators as promising markers of polymyositis/dermatomyositis. Curr Opin Rheumatol 2020; 32: 534-41.
DOI: https://doi.org/10.1097/BOR.0000000000000744
Hatemi G, Mahr A, Ishigatsubo Y, Song Y-W, Takeno M, Kim D, et al. Trial of apremilast for oral ulcers in Behçet’s syndrome. N Engl J Med 2019; 381: 1918-28.
DOI: https://doi.org/10.1056/NEJMoa1816594
Bitar C, Maghfour J, Ho-Pham H, Stumpf B, Boh E. Apremilast as a potential treatment for moderate to severe dermatomyositis: a retrospective study of 3 patients. JAAD Case Rep 2019; 5: 191-4.
DOI: https://doi.org/10.1016/j.jdcr.2018.11.019
Charlton D, Moghadam-Kia S, Smith K, Aggarwal R, English JC, Oddis C V. Refractory cutaneous dermatomyositis with severe scalp pruritus responsive to apremilast. J Clin Rheumatol 2021; 27: S561-2.
DOI: https://doi.org/10.1097/RHU.0000000000000999
Konishi R, Tanaka R, Inoue S, Ichimura Y, Nomura T, Okiyama N. Evaluation of apremilast, an oral phosphodiesterase 4 inhibitor, for refractory cutaneous dermatomyositis: a phase 1b clinical trial. J Dermatol 2022; 49: 118-23.
DOI: https://doi.org/10.1111/1346-8138.16179
Bitar C, Ninh T, Brag K, Foutouhi S, Radosta S, Meyers J, et al. Apremilast in recalcitrant cutaneous dermatomyositis: a nonrandomized controlled trial. JAMA Dermatol 2022; 158: 1357-66.
DOI: https://doi.org/10.1001/jamadermatol.2022.3917
Ma C, Liu M, Cheng Y, Wang X, Zhao Y, Wang K, et al. Therapeutic efficacy and safety of JAK inhibitors in treating polymyositis/dermatomyositis: a single-arm systemic meta-analysis. Front Immunol 2024; 15: 1382728.
DOI: https://doi.org/10.3389/fimmu.2024.1382728
Beckett M, Dutz J, Huang K. Upadacitinib therapy in refractory inflammatory myositis: a case series of 10 patients. RMD Open 2024; 10: e003837.
DOI: https://doi.org/10.1136/rmdopen-2023-003837
Beckett M, Tan J, Bonnardeaux E, Dutz J, Shojania K, To F, et al. Tofacitinib therapy in refractory inflammatory myositis: a retrospective cohort study of 41 patients. Rheumatology 2024; 63: 1432-6.
DOI: https://doi.org/10.1093/rheumatology/kead404
Paik JJ, Lubin G, Gromatzky A, Mudd PN, Ponda MP, Christopher-Stine L. Use of Janus kinase inhibitors in dermatomyositis: a systematic literature review. Clin Exp Rheumatol 2023; 41: 348-58.
DOI: https://doi.org/10.55563/clinexprheumatol/hxin6o
How to Cite
Rizzo, C., Grazzini, S., Conticini, E., Chinoy, H., D’Alessandro, R., Camarda, F., … La Barbera, L. (2025). Small molecules in idiopathic inflammatory myopathies: a systematic review and a multicenter case series about Janus kinase inhibitors and apremilast. Reumatismo. https://doi.org/10.4081/reumatismo.2025.1718
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