Session Type: ACR Concurrent Abstract Session
Session Time: 11:00AM-12:30PM
Background/Purpose: Chronically elevated serum IP-10 (CXCL10) levels, and a prominent “interferon (IFN)-response gene signature” in patients with chronic neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE), CANDLE-like diseases or with gain-of-function mutations in TMEM173/STING with STING-associated vasculopathy with onset in infancy (SAVI), suggested modulation of IFN signaling might be a therapeutic option for patients with some autoinflammatory interferonopathies. The compassionate use program was developed to provide baricitinib (JAK1/JAK2 inhibitor) to CANDLE, CANDLE-like and SAVI patients who have no other comparable or satisfactory treatment options. Potential efficacy of treatment was assessed by a reduction in mean Autoinflammatory Diary Scores (ADS) to < 0.5 (CANDLE and CANDLE-like pt.) and to <1.0 (SAVI pt.) and reduction of steroid doses to <0.15mg/kg/day or by at least 50% reduction from baseline.
Methods: Paired t-tests were used to compare mean ADS and prednisone doses at the last clinic visit to baseline data
Results: Between October 2011 and March 4th, 2016, 18 patients (pt.) have been treated (mean duration 2.3 years, SD±1). 9 of 11 CANDLE pt. and 3 of 4 SAVI pt. achieved an ADS of < 0.5 and < 1.0 at the time of their last visit, respectively. None of 3 CANDLE-like pt. achieved an ADS of < 0.5 (mean ADS for all cohorts decreased from 1.5 ± 0.8 to 0.5 ± 0.5) (p< 0.005), 8 of 10 CANDLE pt. and 2 of 3 CANDLE-like pt. achieved a reduction in steroid doses > than 50% from baseline. 4 of 10 CANDLE pt. discontinued oral steroids completely and continued to have an ADS of <0.5. The only SAVI pt. on steroids at baseline continues at the same dose. Mean total prednisone dose decreased in patients receiving steroids at baseline from 0.7 mg/kg/day (0.2-1.8) to 0.2 mg/kg/day (0-0.8) (p< 0.005). The mean baricitinib dose at last patient visit was 6.9 ± 3.3 mg/day (0.2 mg/kg/day). 13 pt. reported at least 1 serious adverse event (SAE), infection being the most common. 2 CANDLE pt. have been discontinued due to SAEs (avascular necrosis; BK viremia and azotemia). Both pt. subsequently died: the first patient due to underlying liver and kidney disease 18 months after discontinuation of baricitinib, the second patient due to worsening interstitial lung disease with development of respiratory failure 4 months after discontinuation of baricitinib and initiation of another JAK inhibitor. 1 pt. required temporary interruption of baricitinib due to neutropenia, and 4 other pt. had their dose electively reduced after testing positive for BK viremia; patients were asymptomatic. The most common adverse events were upper respiratory infections, cough, and BK viruria (baseline BK virus screening was not performed).
Conclusion: Preliminary efficacy and safety data in 18 patients with autoinflammatory type I Interferonopathies treated with baricitinib are encouraging and suggest that targeting IFN signaling with a JAK1/JAK2 inhibitor may be a successful therapeutic strategy. Monitoring BK viral titers in blood and urine, in addition to other measures of safety and efficacy, may be important in dose selection and the benefit-risk assessment of baricitinib for these patients.
To cite this abstract in AMA style:Montealegre Sanchez GA, Reinhardt A, Brogan P, Chapelle DC, Kim H, Judd S, Kost B, O'Brien M, Goodspeed W, Colbert RA, Waldman M, Stone DL, Gao L, Dare J, Schalm S, Klausmeier TL, Murias S, Berkun Y, Brown D, Carter JD, Eroglu FK, Zlotogorski A, Hashkes P, Wittkowski H, Ramsey S, Ozen S, Almeida de Jesus A, Goldbach-Mansky R. Preliminary Response to JAK1/2 Inhibition with Baricitinib in “Candle”,“Savi” and “Candle-like” Diseases. a New Therapeutic Approach for Type I IFN Mediated Autoinflammatory Diseases [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/preliminary-response-to-jak12-inhibition-with-baricitinib-in-candlesavi-and-candle-like-diseases-a-new-therapeutic-approach-for-type-i-ifn-medi/. Accessed May 22, 2019.
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