Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease

Chen, Zhiwei; Wang, Xiaodong; Ye, Shuang

doi:10.1056/nejmc1900045

Cited by 290 publications

(188 citation statements)

References 4 publications

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“…Successful use of tofacitinib has recently been described for ILD associated with anti-melanoma differentiation-associated protein 5 (anti-MDA5)-positive amyopathic dermatomyositis [172,173].…”

Section: Targeted Synthetic Disease-modifying Antirheumatic Drugs (Tsmentioning

confidence: 99%

Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows

Cassone

Manfredi

Vacchi

et al. 2020

JCM

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Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease affecting 0.5–1% of the population worldwide. Interstitial lung disease (ILD) is a serious pulmonary complication of RA and it is responsible for 10–20% of mortality, with a mean survival of 5–8 years. However, nowadays there are no therapeutic recommendations for the treatment of RA-ILD. Therapeutic options for RA-ILD are complicated by the possible pulmonary toxicity of many disease modifying anti-rheumatic drugs (DMARDs) and by their unclear efficacy on pulmonary disease. Therefore, joint and lung involvement should be evaluated independently of each other for treatment purposes. On the other hand, some similarities between RA-ILD and idiopathic pulmonary fibrosis and the results of the recent INBIULD trial suggest a possible future role for antifibrotic agents. From this perspective, we review the current literature describing the pulmonary effects of drugs (immunosuppressants, conventional, biological and target synthetic DMARDs and antifibrotic agents) in patients with RA and ILD. In addition, we suggest a framework for the management of RA-ILD patients and outline a research agenda to fill the gaps in knowledge about this challenging patient cohort.

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Section: Targeted Synthetic Disease-modifying Antirheumatic Drugs (Tsmentioning

confidence: 99%

Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows

Cassone

Manfredi

Vacchi

et al. 2020

JCM

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“…On the faith of a small case series of four patients, basiliximab, a monoclonal antibody targeting CD25+ activated T cells, could improve patients' survival (105). Similarly, JAK-inhibitors (in this case tofacitinib), which blocks interferon pathways and other proinflammatory cytokine pathways, has shown a promising survival rate improvement (17,106).…”

Section: Biologicsmentioning

confidence: 99%

Inflammatory Myopathy-Related Interstitial Lung Disease: From Pathophysiology to Treatment

Hervier

Uzunhan

2020

Front. Med.

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Inflammatory myopathies (IM) are auto-immune connective tissue diseases characterized by muscle involvement and by extramuscular manifestations. As such, pulmonary manifestations, which mainly include interstitial lung disease (ILD), often darken two out of four distinct IM, namely dermatomyositis and overlapping myositis. Being the initiation site of the disease and being the leading cause of morbidity and mortality, ILD is of major importance in this context. ILD has a heterogeneous expression among the patients, with various onset mode, various radiological pattern, various severity and finally with different prognoses, which are particularly difficult to predict at the time of IM diagnosis. Therefore, ILD is a challenging issue. Treatments are based on steroids and immunosuppressive or targeted therapies. Their respective place is yet poorly codified however and remains often based on clinician expertise. Dedicated clinical trials are lacking to date and are also difficult to build, due to difficulty of constituting large and homogeneous patient groups and to rigorously evaluate disease outcomes. Indeed, pulmonary function tests alone are being regularly defeated in IM, in which respiratory muscles are often involved. Composite scores, bringing together several lung parameters, should thus be developed and validated in the future, to better assess the disease response to treatment. This review aims to describe the current knowledge of IM immuno-pathogenesis, the clinical features associated with IM related-ILD, focusing of both severity and prognosis, and the actual therapeutic approaches.

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“…The efficacy of TOF for anti-MDA5 Ab-positive cADM including refractory cases has been reported previously. [ 4 , 5 ] It has also been suggested that TOF may suppress T cell-derived pro-inflammatory and fibrosis-promoting effects in vitro, and is expected to have a therapeutic effect on intractable ILD associated with cADM. [ 7 ] It is suggested that interferon-gamma (IFN-γ) is deeply involved in the etiology of life-threatening DM with ILD, and TOF, which has an effect of suppressing IFN-γ production from T cells, may be effective for refractory DM with ILD.…”

Section: Discussionmentioning

confidence: 99%

“…[ 2 ] The efficacy of combination therapy with CS and tofacitinib (TOF) has also been reported, and TOF has attracted attention as a useful therapeutic option for cADM-associated ILD. [ 4 ] Moreover, it has been reported that TOF could be effective for refractory anti-MDA5 Ab-positive cADM with ILD. [ 5 ] Although several treatment options have been considered for initial remission induction therapy, therapeutic strategies for relapse cases have not yet been established because there have been no large studies into the long-term prognosis and relapse rate of patients with anti-MDA5 Ab-positive DM after remission.…”

Section: Introductionmentioning

confidence: 99%

Tofacitinib for recurrence of antimelanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis after remission

Ishikawa¹,

Kasuya²,

Fujiwara³

et al. 2020

Medicine

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Rationale: Antimelanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab)-positive clinically amyopathic dermatomyositis (cADM) is frequently complicated with interstitial lung disease (ILD) and has a poor prognosis. Although the short-term prognosis of anti-MDA5 Ab-positive cADM is poor, it has been suggested that the recurrence rate is not higher than that of anti-MDA5 Ab-negative dermatomyositis. Combination therapy with corticosteroids, calcineurin inhibitors, and cyclophosphamide is the gold standard for the remission induction therapy at the onset. Recently, it has been reported that tofacitinib (TOF) could be effective for refractory anti-MDA5 Ab-positive cADM with ILD. Although initial remission induction therapy has been established, therapeutic strategies for relapse cases have not yet been established. Patient concerns: A 57-year-old woman who was diagnosed with anti-MDA5 Ab-positive cADM complicated with ILD. In October 2016, she was treated with prednisolone (PSL), tacrolimus (TAC), and cyclophosphamide (CY). These treatments were successful, and PSL could be tapered. However, she developed strong nausea and general fatigue as adverse events of CY. In April 2018, PSL was discontinued, and maintenance therapy was given with TAC. In July 2018, Gottron's sign and ILD recurred. Skin lesions on the finger were partially ulcerated and ILD was also worsening. We proposed a remission reinduction therapy including CY. However, she was rejected CY from experience with past adverse event of CY. Diagnosis: Based on skin lesions and chest computed tomography (CT) findings, the diagnosis was a recurrence of anti-MDA5 Ab-positive cADM with ILD. Interventions: Treatment by TOF 10 mg and PSL 22.5 mg (0.5 mg/kg equivalent) was introduced in November 2018. Outcomes: After introducing TOF and PSL, her skin lesions and chest CT findings of ILD gradually improved. Six months after the induction of TOF, the skin ulcer was epithelialized. One year after the introduction of TOF, PSL was decreased to 9 mg, and the disease activity did not re-exacerbate. Lessons: This case report is the first report suggesting the effectiveness of TOF for recurrent case of anti-MDA5 Ab-positive cADM with ILD. TOF might be an effective therapeutic option for treating recurrent case of anti-MDA5 Ab-positive cADM.

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Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease

Cited by 290 publications

References 4 publications

Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows

Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows

Inflammatory Myopathy-Related Interstitial Lung Disease: From Pathophysiology to Treatment

Tofacitinib for recurrence of antimelanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis after remission

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