Background/Purpose: Juvenile dermatomyositis (JDM) is a systemic autoimmune disease with a prominent interferon (IFN) signature. Treatment often requires prolonged high-dose steroids and other immunosuppressive medications. In a compassionate use program, we assessed efficacy and safety of baricitinib (JAK 1/2 inhibitor) in active refractory JDM.

Methods: Active (based on ≥3 core set measures (CSM)) and refractory (use of high dose steroids and ≥2 other medications, including ≥1 biologic therapy) patients with JDM were enrolled after washing out biologic agents other than IVIG. Baricitinib was dosed based on weight and renal function. Primary outcome was reduction in symptom daily diary score (DDS) of weakness, fatigue, musculoskeletal pain, and rash. Other assessments included International Myositis Assesment and Clinical Studies (IMACS) disease activity CSMs and Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI). Peripheral 28 gene inteferon-regulated gene (IRG) score and serum CXCL10 (IP-10) were assessed. Paired t-test was used to compare baseline to 24 weeks. Safety and tolerability were also assessed.

Results: Four JDM patients (5.8-20.7 years old) were enrolled (NCT01724580).Patients received baricitinib 4-8 mg/day PO divided BID. After 24 weeks, DDS reduced from a mean of 2.0 (range 1.1-2.3) to 1.0 (0.7-1.1; mean decrease 49%, p=0.02) (Figure or Fig 1A). Physician global activity visual analog scale (VAS) decreased from a mean of 5.1 (3.5-7.4) to 3.9 (3.0-6.1; 24% decrease, p=0.04) (Fig 1B). Extramuscular global activity VAS decreased from mean 5.1 (3.0-7.3) to 3.6 (1.0-5.0; mean 34% decrease, p=0.03). CDASI activity score reduced from mean 43 (27-53) to 26 (14-48; mean improvement 41%, p=0.04) (Fig 1C). In 2/4 with baseline weakness, manual muscle testing (MMT8) increased from 108 to 135 and 116 to 142 (mean improvement 24%) (Fig 1D). By the ACR-EULAR JDM response criteria, the Total Improvement Score (TIS) was mean 39, range 17.5-62.5. In 2 pts with baseline weakness, the TIS improved moderately, with a change of 55 and 62.5. Two patients reduced prednisone (21 to 15 and 10 to 7.5 mg/day); 2 patients’ doses remained unchanged (5 and 10 mg/day). Baricitinib was generally well tolerated. One patient had an increase in plasma BK viral titer; the other 3 patients were negative for BK virus in blood and urine. No adverse events required holding/discontinuing baricitinib. IRG score was significantly lower at 24 weeks (p value < 0.01) and serum IP-10 at 12 weeks was trending lower (p= 0.056).

Conclusion: Preliminary data on the use of baricitinib (JAK 1/2 inhibitor) in 4 refractory JDM patients are encouraging, showing improvement in symptom DDS as well as in validated measures of rash (4/4) and strength (2/2 with baseline weakness), and other CSMs. Patients with baseline weakness met clinically significant moderate improvement by the ACR-EULAR response criteria. A corresponding decrease in IRG and trend down in IP-10 was observed. Baricitinib was generally well tolerated and further evaluation in JDM should be considered.

Disclosures: Baricitinib provided by Eli Lilly and Company, expanded access program sponsor. Other support: IRP of NIH, NIAMS, NIEHS, CC.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/preliminary-response-to-janus-kinase-jak-inhibition-with-baricitinib-in-refractory-juvenile-dermatomyositis/