Janus kinase (JAK) inhibition with baricitinib in refractory juvenile dermatomyositis

Kim, Susan; Dill, Samantha; O’Brien, Michelle; Vian, Laura; Li, Xiaobai; Manukyan, Manuk; Jain, Minal; Adeojo, Lilian W; George, Jomy; Pérez, Milagros Bernal; Grom, Alexei A.; Sutter, Michelle De; Feldman, Brian M.; Yao, Lawrence; Millwood, Michelle; Brundidge, April; Pichard, Dominique C.; Cowen, Edward W.; Shi, Yingying; Lu, Shajia; Tsai, Wanxia Li; Gadina, Massimo; Rider, Lisa G.; Colbert, Robert A.

doi:10.1136/annrheumdis-2020-218690

Cited by 60 publications

(54 citation statements)

References 6 publications

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“…This approach limits the cumulative glucocorticoid exposure and potential longterm adverse events. As increasing numbers of other immunomodulatory agents are investigated in the treatment of JDM (37)(38)(39), ideally cumulative steroid exposure will continue to decrease. JDM (Juvenile Dermatomyositis), IVMP (intravenous pulse methylprednisolone), CARRA (Childhood Arthritis and Rheumatology Research Alliance), MRI (magnetic resonance imaging), IVIG (intravenous immune globulin), PRINTO (Paediatric Rheumatology International Trials Organization)…”

Section: Resultsmentioning

confidence: 99%

Favorable Outcomes with Reduced Steroid Use in Juvenile Dermatomyositis

Orandi

Fotis

Lai

et al. 2021

Preprint

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Background High-intensity glucocorticoid regimens are commonly used to induce and maintain remission in Juvenile Dermatomyositis (JDM) but are associated with several adverse side-effects. Eminence-based treatment guidelines from CARRA and SHARE both advocate induction of intravenous pulse steroids followed by high dose oral steroids (2 mg/kg) tapered over 12 months. This study compares the time to disease control with reduced glucocorticoid dosing. Methods We retrospectively reviewed the records at a single tertiary-care children’s hospital of patients with JDM between 2000 and 2014 who had a minimum of 2 years of follow-up. The primary outcome measure was time to control of muscle and skin disease. Additional outcome measures included glucocorticoid dosing, effect of treatment on height, frequency of calcinosis and complications from treatment. Results Of the 69 patients followed during the study period, 31 fulfilled inclusion criteria. Median length of follow-up was 4.58 years, (3–7.5). Myositis control was achieved in a median of 7.1 months (range 0.9–63.4). Cutaneous disease control was achieved in a median of 16.7 months (range 4.3–89.5). The median starting dose of glucocorticoids was 0.85 mg/kg/day, (range 0.5–1.74). The median duration of steroid treatment was 9.1 months, (range 4.7–17.4), while the median duration of any pharmacotherapy was 29.2 months (range 10.4 to 121.3). Sustained disease control off medications was achieved in 21/31 (68%) patients by the end of review. Persistent calcinosis was identified in only one patient (3%). Conclusion Current accepted treatment paradigms for JDM include oral glucocorticoids beginning at 2 mg/kg/d reduced over 12 months; however, our results suggest that treatment using reduced doses and durations with early use of steroid-sparing agents are comparably effective in achieving favorable outcomes in JDM.

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Section: Resultsmentioning

confidence: 99%

Favorable Outcomes with Reduced Steroid Use in Juvenile Dermatomyositis

Orandi

Fotis

Lai

et al. 2021

Preprint

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“…However, a randomized control trial would be necessary to definitively determine if lower dose steroids are sufficient or if higher dose regiments are needed in JDM. As increasing numbers of other immunomodulatory agents are investigated in the treatment of JDM [ 39 – 41 ], ideally cumulative steroid exposure will continue to decrease.…”

Section: Discussionmentioning

confidence: 99%

Favorable outcomes with reduced steroid use in juvenile dermatomyositis

et al. 2021

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Background High-intensity glucocorticoid regimens are commonly used to induce and maintain remission in Juvenile Dermatomyositis but are associated with several adverse side-effects. Evidence-based treatment guidelines from North American and European pediatric rheumatology research societies both advocate induction with intravenous pulse steroids followed by high dose oral steroids (2 mg/kg/day), which are then tapered. This study reports the time to disease control with reduced glucocorticoid dosing. Methods We retrospectively reviewed the records at a single tertiary-care children’s hospital of patients diagnosed with Juvenile Dermatomyositis between 2000 and 2014 who had a minimum of 2 years of follow-up. The primary outcome measure was time to control of muscle and skin disease. Additional outcome measures included glucocorticoid dosing, effect of treatment on height, frequency of calcinosis, and complications from treatment. Results Of the 69 patients followed during the study period, 31 fulfilled inclusion criteria. Median length of follow-up was 4.58 years, (IQR 3–7.5). Myositis control was achieved in a median of 7.1 months (IQR 0.9–63.4). Cutaneous disease control was achieved in a median of 16.7 months (IQR 4.3–89.5). The median starting dose of glucocorticoids was 0.85 mg/kg/day, (IQR 0.5–1.74). The median duration of steroid treatment was 9.1 months, (IQR 4.7–17.4), while the median duration of any pharmacotherapy was 29.2 months (IQR 10.4 to 121.3). Sustained disease control off medications was achieved in 21/31 (68%) patients by the end of review. Persistent calcinosis was identified in only one patient (3%). Conclusion Current accepted treatment paradigms for Juvenile Dermatomyositis include oral glucocorticoids beginning at 2 mg/kg/day and reduced over a prolonged time period. However, our results suggest that treatment using reduced doses and duration with early use of steroid-sparing agents is comparably effective in achieving favorable outcomes in Juvenile Dermatomyositis.

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“…Recent reports highlight the beneficial effects of Janus kinase inhibitors (tofacitinib, ruxolitinib, baricitinib) in children and adults with both newly diagnosed and refractory DM [47,48]. A randomized phase IIa study is currently being conducted to assess the efficacy and safety of baricitinib in adult patients with IIM (EudraCT Number: 2019-003868-42).…”

Section: Janus Kinase Inhibitorsmentioning

confidence: 99%

“…Ostatnie doniesienia zwracają uwagę na korzystne efekty zastosowania inhibitorów kinaz janusowych (tofacytynibu, ruksolitynibu, baricytynibu) u dzieci i dorosłych zarówno z nowo rozpoznanym, jak i opornym na leczenie DM [47,48]. Aktualnie toczy się badanie fazy IIa z randomizacją oceniające skuteczność i bezpieczeństwo stosowania baricytynibu u dorosłych pacjentów chorujących na IIM (EudraCT Number: 2019-003868-42).…”

Section: Inhibitory Kinaz Janusowychunclassified

Dermatomyositis. Diagnostic and therapeutic recommendations of the Polish Dermatological Society

Reich¹,

Lis‐Święty²,

Krasowska³

et al. 2021

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Dermatomyositis is an autoimmune disease characterized by skin lesions and/or symptoms of myositis. In addition to the so-called classic dermatomyositis the following forms of dermatomyositis are distinguished based on the clinical presentation: pediatric, paraneoplastic, drug-induced and amyopathic. A number of disease-specific autoantibodies are identified in dermatomyositis (including anti-Mi2, anti-TIF1, anti-NXP2, anti-SAE or anti-MDA5), presence of which may be associated with a specific clinical phenotype. The diagnosis of the severity of muscle involvement is currently based mainly on physical examination, deviations in results of laboratory investigations, electromyographic examination and imaging examination, mainly with the use of magnetic resonance imaging. Systemic glucocorticosteroids administered as monotherapy or in combination with other immunosuppressants remain the mainstay of dermatomyositis treatment, and in the absence of satisfactory improvement, intravenous immunoglobulins are used. In addition, in case of interstitial lung disease, the use of cyclophosphamide may be necessary. The choice of a therapy, as well as the rate of dose reduction, depend on the dynamics of the disease, symptoms, diagnosed immunological disorders, as well as comorbidities and the drugs used. Each diagnostic and therapeutic decision must take into account the individual clinical data of the patient and current scientific reports.

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Janus kinase (JAK) inhibition with baricitinib in refractory juvenile dermatomyositis

Cited by 60 publications

References 6 publications

Favorable Outcomes with Reduced Steroid Use in Juvenile Dermatomyositis

Favorable Outcomes with Reduced Steroid Use in Juvenile Dermatomyositis

Favorable outcomes with reduced steroid use in juvenile dermatomyositis

Dermatomyositis. Diagnostic and therapeutic recommendations of the Polish Dermatological Society

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