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Clinical Trial
. 2020 Sep 3;383(10):986-989.
doi: 10.1056/NEJMc2001362.

Janus Kinase Inhibition in the Aicardi-Goutières Syndrome

Adeline Vanderver  1 , Laura Adang  1 , Francesco Gavazzi  1 , Katherine McDonald  1 , Guy Helman  2 , David B Frank  3 , Nicole Jaffe  3 , Sabrina W Yum  3 , Abigail Collins  4 , Stephanie R Keller  5 , Pierre Lebon  6 , Jean-François Meritet  7 , Jullie Rhee  8 , Asako Takanohashi  3 , Thais Armangue  9 , Nicole Ulrick  3 , Omar Sherbini  3 , Jamie Koh  3 , Kyle Peer  3 , Constance Besnier  3 , Carly Scher  3 , Katherine Boyle  3 , Holly Dubbs  3 , Julia Kramer-Golinkoff  3 , Amy Pizzino  3 , Sarah Woidill  3 , Justine Shults  10
Affiliations
Clinical Trial

Janus Kinase Inhibition in the Aicardi-Goutières Syndrome

Adeline Vanderver et al. N Engl J Med. .
No abstract available

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Figures

Figure 1.
Figure 1.. Changes in Symptoms, Interferon Gene Expression, and Developmental Skills in Children with the Aicardi–Goutières Syndrome.
As shown in Panel A, a decrease in symptoms during the study was indicated by reduced skin inflammation in the neck, face, toes, and hands of the patients. In Patient 1, the findings shown are from 3 days after the initiation of treatment; in Patient 2, from 1 month after the initiation of treatment; and in Patient 3, from the 18-month visit (the clinical cutoff date for data analysis). As shown in Panel B, the interferon-signaling gene (ISG) expression scores decreased during treatment. This score is calculated from the expression of six interferon-signaling genes normalized to housekeeping genes. The six-gene interferon signature is the sum of the median z scores of these genes. The interferon signature is positive (i.e., type 1 interferon signaling is high) if it is at least 1.96 (>98th percentile) on a one-tailed test (see Section 3.1.6 in the Supplementary Appendix). As shown in Panel C, symptom scores recorded in diaries by the patients’ parents decreased during treatment. Recorded symptoms were neurologic disability, crying, sleep disturbances, irritability, seizures, fever, and skin inflammation of the trunk, arms, and legs (see the Supplemental Methods section and Table S5 in the Supplementary Appendix). As shown in Panel D, developmental milestones in the individual patients were met during treatment. Each bar represents an individual patient. As shown in Panel E, the gain of new milestones correlated with the dose of baricitinib. Target doses varied according to weight-based norms (see the Supplementary Methods section in the Supplementary Appendix). In Panels B, C, and E, each circle represents an individual patient. Horizontal lines indicate means, and I bars standard deviations.
See this image and copyright information in PMC

Comment in

  • JAK Inhibition in the Aicardi-Goutières Syndrome.
    Neven B, Al Adba B, Hully M, Desguerre I, Pressiat C, Boddaert N, Duffy D, Rice GI, Seabra L, Frémond ML, Blanche S, Crow YJ. Neven B, et al. N Engl J Med. 2020 Nov 26;383(22):2190-2191. doi: 10.1056/NEJMc2031081. N Engl J Med. 2020. PMID: 33252884 No abstract available.

References

    1. Rice G, Patrick T, Parmar R, et al. Clinical and molecular phenotype of Aicardi-Goutieres syndrome. Am J Hum Genet 2007;81:713–25. - PMC - PubMed
    1. Briand C, Frémond M-L, Bessis D, et al. Efficacy of JAK1/2 inhibition in the treatment of chilblain lupus due to TREX1 deficiency. Ann Rheum Dis 2019;78:431–3. - PubMed
    1. Kothur K, Bandodkar S, Chu S, et al. An open-label trial of JAK 1/2 blockade in progressive IFIH1-associated neuroinflammation. Neurology 2018;90:289–91. - PubMed
    1. Montealegre Sanchez GA, Reinhardt A, Ramsey S, et al. JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies. J Clin Invest 2018;128:3041–52. - PMC - PubMed
    1. Adang LA, Frank DB, Gilani A, et al. Aicardi Goutières syndrome is associated with pulmonary hypertension. Mol Genet Metab 2018;125:351–8. - PMC - PubMed

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