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JAAD Case Rep
JAAD Case Rep
JAAD Case Reports
2352-5126
Elsevier

S2352-5126(24)00261-3
10.1016/j.jdcr.2024.06.033
Case Report
Successful treatment of refractory amyopathic dermatomyositis with upadacitinib in prior JAK inhibitor failure
Sohn Alice BS a
Bouché Nicole BS b
Lewitt George Michael MD c
Song Eingun James MD Eingun.Song@frontierdermpartners.com
a∗
a Frontier Dermatology, Mill Creek, Washington
b Elson S. Floyd College of Medicine, Spokane, Washington
c Illinois Dermatology Institute, Chicago, Illinois
∗ Correspondence to: Eingun James Song, MD, Frontier Dermatology, 15906 Mill Creek Blvd #105, Mill Creek, WA 98012. Eingun.Song@frontierdermpartners.com
08 7 2024
9 2024
08 7 2024
51 9799
© 2024 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.
2024
American Academy of Dermatology, Inc.
https://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Key words

biologics
clinical research
dermatomyositis
drug response
general dermatology
immunodermatology
Medical Dermatology
upadacitnib
Abbreviations used

ADM amyopathic dermatomyositis

DM dermatomyositis

IFN interferon

JAK Janus kinase
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pmcIntroduction

Dermatomyositis (DM) is a chronic idiopathic inflammatory condition involving the skin and muscles that classically presents with a heliotrope rash and Gottron’s papules.1 Intravenous immune globulin is currently the only FDA-approved treatment for DM. Other treatments include photoprotection, topical corticosteroids, antimalarials, and traditional systemic immunosuppressants.1 Unfortunately, many patients are treatment refractory, highlighting the need for additional effective and safe therapies.

Recent studies have demonstrated upregulation of the type 1 interferon (IFN) pathway to be associated with DM. Indeed, treatment with IFN beta-1a therapy for multiple sclerosis has been reported to trigger DM,2 while inhibiting IFN signaling has been shown to be beneficial in DM.1,3,4 Because type 1 IFNs signal through the Janus kinase (JAK) pathway, JAK inhibitors have been used off-label to treat DM.5 Upadacitinib is an oral JAK-1 (JAK1) inhibitor that has been approved for the treatment of multiple immune-mediated inflammatory diseases including rheumatoid arthritis, psoriatic arthritis, and atopic dermatitis. Herein, we report a case of amyopathic DM (ADM) refractory to baricitinib but experienced significant improvement upon treatment with upadacitinib.

Case report

A 66-year-old woman presented to our clinic for evaluation of a long-standing, widespread, pruritic eruption involving her scalp, trunk, arms, and legs. On examination, she had erythematous to violaceous psoriasiform patches and plaques involving most of the scalp, neck, chest, back, extensor arms, hands, and thighs (Fig 1). Histopathology showed an interface dermatitis consistent with DM (Fig 2). Her workup was notable for a positive antinuclear antibody 1:160 with a speckled pattern and anti-Jo1 antibody (negative for transcriptional intermediary factor 1-γ, nuclear matrix protein 2, and anti-melanoma differentiation-associated gene 5). Age-appropriate cancer screening was negative and baseline pulmonary function tests were within normal limits. The patient demonstrated 5/5 muscle strength with normal muscle enzymes and was subsequently diagnosed with ADM.Fig 1 Initial presentation before treatment.

Fig 2 Hematoxylin and eosin (10× magnification) demonstrating a mild lichenoid lymphocytic infiltrate with prominent interface vacuolar change.

The patient was initially treated with topical corticosteroids, hydroxychloroquine, and methotrexate with minimal improvement. The patient demonstrated the most improvement with baricitinib 4 mg daily, but still had significant itching and skin disease after 3 months of treatment.

Decision was made to try off-label use of upadacitinib 30 mg daily, which resulted in substantial improvement in skin clearance and itch reduction following 3 months of treatment (Fig 3). Patient tolerated the medication well without any notable laboratory changes. As of today’s writing, the patient has been on upadacitinib for 6 months and continues to be almost clear.Fig 3 Three months after treatment with upadacitinib 30 mg daily.

Discussion

Enhanced type 1 IFN signaling has been shown to be involved in a number of autoimmune diseases, including DM.4,6 Given the obligate role of the JAK pathway in IFN signaling, JAK inhibitors have been used off-label to treat DM, with tofactinib and baricitinb being the most frequently reported.1 Brepocitinib, a dual tyrosine kinase 2 and JAK1 inhibitor, is currently being evaluated in phase III clinical trials for adults with DM and is poised to be the first JAK inhibitor approved for DM.7

While there is less published data with upadacitinib, Beckett et al recently reported a case series of 10 patients with myositis who were successfully treated with upadacitinib (5 patients with classic DM, 3 with ADM, and 2 with antisynthetase syndrome). Those diagnosed with classic DM and ADM experienced significant improvement of their cutaneous symptoms upon treatment with upadacitinib.8

Our patient’s prior failure to baricitinib highlights the inherent differences among therapies even within the same class. Differences in JAK selectivity, the mode of target binding, drug metabolism, and tissue penetration may lead to differences in the clinical profile of a particular JAK inhibitor.9 Because type 1 IFN signaling is primarily mediated by JAK1/tyrosine kinase 2, selective JAK1 inhibitors such as upadacitinib may be more effective in DM.10 Furthermore, individual variations such as single-nucleotide polymorphisms that can affect signal transducer and activation of transcription isoforms and differential JAK expression at sites of inflammation may also account for treatment response differences.11 Indeed, studies have shown in rheumatoid arthritis that prior JAK inhibitor failure should not preclude switching to another JAK inhibitor.12

Being a single case report, there are limitations including sample size and short duration of follow-up. As with most cases of off-label usage, our patient’s insurance would not approve upadacitinib for her indication and therefore has been managed with samples. Longer-term data will be of utmost importance given the paraneoplastic association with DM and the increased risk of malignancy seen in high-risk rheumatoid arthritis patients treated with oral tofacitinib.13

Conflicts of interest

Dr Lewitt reports relationship with AbbVie, Amgen, Lilly, Janssen, Orthodermatologics, UCB, Novartis, Pfizer, Dermavant, Bristol Myers Squibb, Incyte, Arcutis, Sol-Gel, AoBiome, Galderma Laboratories, Leo, Novan, Derm-Tech, and Dermata-Therapeutics; Dr Song reports relationship with BMS, AbbVie, Eli Lilly, Janssen, Novartis, UCB, Pfizer, Amgen, Dermavant, Arcutis, Incyte, SUN, Boehringer Ingelheim, Sanofi & Regeneron, and Ortho-dermatologics. Drs Sohn and Bouché have no conflicts of interest to declare.

Funding sources: None.

Patient consent: The authors obtained written consent from patients for their photographs and medical information to be published in print and online and with the understanding that this information may be publicly available. Patient consent forms were not provided to the journal but are retained by the authors.

IRB approval status: Not applicable.
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References

1 Paik J.J. Lubin G. Gromatzky A. Mudd P.N. Ponda M.P. Christopher-Stine L. Use of JAK inhibitors in dermatomyositis: a systematic literature review Clin Exp Rheumatol 41 2 2023 348 358 10.55563/clinexprheumatol/hxin6o 35766013
2 Somani A.K. Swick A.R. Cooper K.D. McCormick T.S. Severe dermatomyositis triggered by interferon beta-1a therapy and associated with enhanced type I interferon signaling Arch Dermatol 144 10 2008 1341 1349 10.1001/archderm.144.10.1341 18936398
3 Ang P.S. Ezenwa E. Ko K. Hoffman M.D. Refractory dermatomyositis responsive to anifrolumab JAAD Case Rep 43 2023 27 29 10.1016/j.jdcr.2023.10.023 38162409
4 Baechler E.C. Bilgic H. Reed A.M. Type I interferon pathway in adult and juvenile dermatomyositis Arthritis Res Ther 13 6 2011 249 10.1186/ar3531 22192711
5 Min M.S. Alsarheed A. Kassamali B. Tofacitinib as treatment for refractory dermatomyositis: a retrospective study from 2 academic medical centers J Am Acad Dermatol 86 2 2022 423 425 10.1016/j.jaad.2021.07.003 34246697
6 Huard C. Gullà S.V. Bennett D.V. Coyle A.J. Vleugels R.A. Greenberg S.A. Correlation of cutaneous disease activity with type 1 interferon gene signature and interferon β in dermatomyositis Br J Dermatol 176 5 2017 1224 1230 10.1111/bjd.15006 27564228
7 Priovant Therapeutics, Inc. A phase 3, randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of oral brepocitinib in adults with dermatomyositis. clinicaltrials.gov https://clinicaltrials.gov/study/NCT05437263 2024
8 Beckett M. Dutz J. Huang K. Upadacitinib therapy in refractory inflammatory myositis: a case series of 10 patients RMD Open 10 1 2024 e003837 10.1136/rmdopen-2023-003837
9 Taylor P.C. Choy E. Baraliakos X. Differential properties of Janus kinase inhibitors in the treatment of immune-mediated inflammatory diseases Rheumatology 63 2 2024 298 308 10.1093/rheumatology/kead448 37624925
10 Traves P.G. Murray B. Campigotto F. Galien R. Meng A. Di Paolo J.A. JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib Ann Rheum Dis 80 7 2021 865 875 10.1136/annrheumdis-2020-219012 33741556
11 Tanaka Y. Luo Y. O'Shea J.J. Nakayamada S. Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach Nat Rev Rheumatol 18 3 2022 133 145 10.1038/s41584-021-00726-8 34987201
12 Amstad A. Papagiannoulis E. Scherer A. Comparison of drug retention of TNF inhibitors, other biologics and JAK inhibitors in RA patients who discontinued JAK inhibitor therapy Rheumatology (Oxford) 62 1 2022 89 97 10.1093/rheumatology/keac285 35579338
13 Ytterberg S.R. Bhatt D.L. Mikuls T.R. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis N Engl J Med 386 4 2022 316 326 10.1056/NEJMoa2109927 35081280
