- Indian Rheumatology association
Devang B Pandya
Consultant Paediatric Rheumatologist & Immunologist, Krish Superspeciality Clinic, Ahmedabad
Recently, there has been an emerging interest of interferon in the pathogenesis of Juvenile Dermatomyositis (JDM). JAK inhibitors have yielded satisfactory responses in treating interferonopathies and refractory JDM.
Zhang et al, included 83 children (age < 18 years) who received tofacitinib (>/=3months) in view of active skin disease, muscle disease or failure with previous cDMARDs or biologics. Efficacy of tofacitinib has been established using International Myositis Assessment and Clinical Studies Group (IMACS) complete clinical response which is defined as more than 6 months of inactive disease (e.g., normal muscle strength, no skin rashes, and normal kinase under myositis treatment). Sixteen (18.2%), 42(47.7%) and 37(42.0%) patients reached IMACS-defined complete clinical response after 6, 9 and 12 months respectively. In general, 44 (50%) refractory patients reached complete clinical response at the last follow up. Two (2.3%) of them had escalation in their background medications. Median dose of Glucocorticoids (GC) was 0.05mg/kg and 10/83(12%) were off-GC. Fifty-three (60.2%) patients presented with pulmonary involvement recovered with no respiratory symptoms and had a reduction in the size or number of lesions under high-resolution computerized tomography (HRCT) scans of lung. Fifteen patients (75%) presented with calcinosis showed a reduction in the size or number, five patients (25%) showed complete resolution and three (3.4%) patients developed new lesions after starting tofacitinib. Only one patient had herpes zoster infection in 9 months after initiation. After drug withdrawal, herpes recovered and tofacitinib was given again.
This study shows the potential benefits & safety of JAK inhibitor – Tofacitinib in refractory JDM in all components: Skin , Muscle , Calcinosis and Lung involvement.
There is no universal therapeutic agent for Auto inflammatory diseases (AIDs) and treatment options are very much limited. Another dilemma is a few effective targeted biological agents like IL-1 inhibitors and others are either unavailable or non-affordable in an Indian setting. Thalidomide has a promising real world data in systemic juvenile idiopathic arthritis (sJIA) from India which is again a polygenic auto inflammatory disease with similar pathogenesis.
This study from China included 16 children (<18 years) with active inflammation despite glucocorticoids(GC), immunosuppressive (IS) or biologics. All patients who completed 3 months run-in period, were given Thalidomide (1-2mg/kg/day, max 50mg) for 12 months without altering their background medications. Four children out of 16 were withdrawn from the study at first 3 months interval due to no clinical benefit, or side effects or required escalation in their background medications. Efficacy was measured in terms of clinical improvement (predominantly fever, rash and others as per particular disease), reduction in inflammatory markers and de-escalation of background medications at 12 months. Clinical improvement was noted in 10/12 (83.3%) children. Reduction in values of CRP & ESR was significant (P=0.002, 0.014) from baseline. Three out of 12 (25.0%) patients were off GC and IS and 1/12 (8.3%) patient discontinued the biologic agent. None of these 12 patients had adverse events such as peripheral neuropathy and somnolence. The small sample size, retrospective design, efficacy parameters and heterogeneity in the study group are important limitations of the study.
