Discussion
death, pneumonia, intracranial hemorrhage, TEAEs, infections, AGS, nontuberculous mycobacterium infection, polyomavirus infection, upper respiratory tract infections
PNEUMONIA, UPPER RESPIRATORY TRACT INFECTIONS, INTRACRANIAL HEMORRHAGE, INFECTIONS, PGA, AUTOINFLAMMATORY DISEASE, ASPERGILLUS INFECTION
Our study was the first that evaluated the efficacy and safety of baricitinib in Japanese patients with autoinflammatory interferonopathies, NNS/CANDLE, SAVI, or AGS. The overall reduction in mean DDS from baseline in patients with NNS/CANDLE or SAVI at the end of the primary treatment period and maintenance period demonstrated consistent efficacy. Decrease in PGA score and DSSS, consequently leading to decrease in corticosteroid use, reinforced the efficacy of baricitinib in patients with these rare autoinflammatory type I interferonopathies. Four (44.4%) of 9 patients had mild TEAEs, and infections were the most frequently reported. SAEs observed at the end of the primary treatment period were not reported at the end of the maintenance period, and 1 SAE was deemed related to the study drug. Two patients with NNS/CANDLE and SAVI discontinued study due to AE and death, respectively. The patient with SAVI had SAEs, including pneumonia due to aspergillus infection and nontuberculous mycobacterium infection, who consequently died. As per the study investigator, the SAEs were related to the study drug, as the drug was immunosuppressive. However, the death due to intracranial hemorrhage was not deemed to be related to the study drug, as the study drug was discontinued three months prior due to The results of our study were comparable to the baricitinib trial conducted as an expanded access program in patients with type I IFN-mediated autoinflammatory diseases (JAGA trial; NCT01724580) [Our data showed a smaller proportion of patients with upper respiratory tract infections (22.2% vs 77.8%) and BK polyomavirus infection (33.3% vs 50%) than the JAGA trial [BK polyomavirus positivity in patients treated with baricitinib was consistent between our study and the JAGA trial. Safety was assessed and BK viral load was monitored in 7 additional patients after the JAGA trial. Of the total 23 patients in the trial, 20 (87%) developed BK viruria [The study had limitations including small sample size, heterogenous patient population, absence of comparators and randomization, use of immunosuppressive concomitant medications, and presence of clinically significant preexisting conditions, leading to potential bias. However, although the enrolled Japanese patient population was small, open label baricitinib consistently decreased mean DDS across 52 weeks. Overall, the drug was well tolerated, but physicians need to be cautious of BK polyomavirus. Continuation of this trial would further provide clarity on the long-term effect and benefit/risk ratio of baricitinib in patients with NNS/CANDLE, SAVI, or AGS.