Disease flares with baricitinib dose reductions and development of flare criteria in patients with CANDLE/PRAAS

Kader Cetin Gedik, Ana M. Ortega-Villa, Grace Materne, Andre Rastegar, Gina A. Montealegre Sanchez, Adam Reinhardt, Paul A. Brogan, Yackov Berkun, Sara Murias, Maria Robles, Susanne Schalm, Adriana A. De Jesus, Raphaela Goldbach-Mansky

Research output: Contribution to journalArticlepeer-review


Objectives: Patients with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS) respond to the janus kinase inhibitor 1/2 inhibition with baricitinib at exposures higher than in rheumatoid arthritis. Baricitinib dose reductions to minimise exposure triggered disease flares which we used to develop € flare criteria'. Methods: Of 10 patients with CANDLE/PRAAS treated with baricitinib in an open-label expanded-access programme, baricitinib doses were reduced 14 times in 9 patients between April 2014 and December 2019. Retrospective data analysis of daily diary scores and laboratory markers collected before and after the dose reductions were used to develop € clinical' and € subclinical' flare criteria. Disease flare rates were compared among patients with <25% and >25% dose reductions and during study visits when patients received recommended € optimized' baricitinib doses (high-dose visits) versus lower than recommended baricitinib doses (low-dose visits) using two-sided χ2 tests. Results: In the 9/10 patients with CANDLE with dose reduction, 7/14 (50%) times the dose was reduced resulted in a disease flare. All four dose reductions of >25% triggered a disease flare (p <0.05). Assessment of clinical and laboratory changes during disease flares allowed the development of disease flare criteria that were assessed during visits when patients received high or low doses of baricitinib. Disease flare criteria were reached during 43.14% of low-dose visits compared with 12.75% of high-dose visits (p <0.0001). Addition of an interferon score as an additional flare criterion increased the sensitivity to detect disease flares. Conclusion: We observed disease flares and rebound inflammation with baricitinib dose reductions and proposed flare criteria that can assist in monitoring disease activity and in designing clinical studies in CANDLE/PRAAS.

Original languageEnglish (US)
Article numberard-2023-225463
JournalAnnals of the rheumatic diseases
StateAccepted/In press - 2024


  • Immune System Diseases
  • Inflammation
  • Outcome Assessment, Health Care

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • General Biochemistry, Genetics and Molecular Biology


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