Basit öğe kaydını göster

dc.contributor.authorSanchez, Gina A. Montealegre
dc.contributor.authorReinhardt, Adam
dc.contributor.authorRamsey, Suzanne
dc.contributor.authorWittkowski, Helmut
dc.contributor.authorHashkes, Philip J.
dc.contributor.authorBerkun, Yackov
dc.contributor.authorSchalm, Susanne
dc.contributor.authorMurias, Sara
dc.contributor.authorDare, Jason A.
dc.contributor.authorBrown, Diane
dc.contributor.authorStone, Deborah L.
dc.contributor.authorGao, Ling
dc.contributor.authorKlausmeier, Thomas
dc.contributor.authorFoell, Dirk
dc.contributor.authorde Jesus, Adriana A.
dc.contributor.authorChapelle, Dawn C.
dc.contributor.authorKim, Hanna
dc.contributor.authorDill, Samantha
dc.contributor.authorColbert, Robert A.
dc.contributor.authorFailla, Laura
dc.contributor.authorKost, Bahar
dc.contributor.authorO’Brien, Michelle
dc.contributor.authorReynolds, James C.
dc.contributor.authorFolio, Les R.
dc.contributor.authorCalvo, Katherine R.
dc.contributor.authorPaul, Scott M.
dc.contributor.authorWeir, Nargues
dc.contributor.authorBrofferio, Alessandra
dc.contributor.authorSoldatos, Ariane
dc.contributor.authorBiancotto, Angelique
dc.contributor.authorCowen, Edward W.
dc.contributor.authorDigiovanna, John J.
dc.contributor.authorGadina, Massimo
dc.contributor.authorLipton, Andrew J.
dc.contributor.authorHadigan, Colleen
dc.contributor.authorHolland, Steven M.
dc.contributor.authorFontana, Joseph
dc.contributor.authorAlawad, Ahmad S.
dc.contributor.authorBrown, Rebecca J.
dc.contributor.authorRother, Kristina I.
dc.contributor.authorHeller, Theo
dc.contributor.authorBrooks, Kristina M.
dc.contributor.authorKumar, Parag
dc.contributor.authorBrooks, Stephen R.
dc.contributor.authorWaldman, Meryl
dc.contributor.authorSingh, Harsharan K.
dc.contributor.authorNickeleit, Volker
dc.contributor.authorSilk, Maria
dc.contributor.authorPrakash, Apurva
dc.contributor.authorJanes, Jonathan M.
dc.contributor.authorOzen, Seza
dc.contributor.authorWakim, Paul G.
dc.contributor.authorBrogan, Paul A.
dc.contributor.authorMacias, William L.
dc.contributor.authorGoldbach-Mansky, Raphaela
dc.date.accessioned2019-12-10T10:39:21Z
dc.date.available2019-12-10T10:39:21Z
dc.identifier.issn0021-9738
dc.identifier.urihttps://doi.org/10.1172/JCI98814
dc.identifier.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026004/
dc.identifier.urihttp://hdl.handle.net/11655/14117
dc.description.abstractBACKGROUND. Monogenic IFN–mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN response gene signature, inflammatory organ damage, and high mortality. We used the JAK inhibitor baricitinib, with IFN-blocking activity in vitro, to ameliorate disease., METHODS. Between October 2011 and February 2017, 10 patients with CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), 4 patients with SAVI (stimulator of IFN genes–associated [STING-associated] vasculopathy with onset in infancy), and 4 patients with other interferonopathies were enrolled in an expanded access program. The patients underwent dose escalation, and the benefit was assessed by reductions in daily disease symptoms and corticosteroid requirement. Quality of life, organ inflammation, changes in IFN-induced biomarkers, and safety were longitudinally assessed., RESULTS. Eighteen patients were treated for a mean duration of 3.0 years (1.5–4.9 years). The median daily symptom score decreased from 1.3 (interquartile range [IQR], 0.93–1.78) to 0.25 (IQR, 0.1–0.63) (P < 0.0001). In 14 patients receiving corticosteroids at baseline, daily prednisone doses decreased from 0.44 mg/kg/day (IQR, 0.31–1.09) to 0.11 mg/kg/day (IQR, 0.02–0.24) (P < 0.01), and 5 of 10 patients with CANDLE achieved lasting clinical remission. The patients’ quality of life and height and bone mineral density Z-scores significantly improved, and their IFN biomarkers decreased. Three patients, two of whom had genetically undefined conditions, discontinued treatment because of lack of efficacy, and one CANDLE patient discontinued treatment because of BK viremia and azotemia. The most common adverse events were upper respiratory infections, gastroenteritis, and BK viruria and viremia., CONCLUSION. Upon baricitinib treatment, clinical manifestations and inflammatory and IFN biomarkers improved in patients with the monogenic interferonopathies CANDLE, SAVI, and other interferonopathies. Monitoring safety and efficacy is important in benefit-risk assessment., TRIAL REGISTRATION. ClinicalTrials.gov NCT01724580 and NCT02974595., FUNDING. This research was supported by the Intramural Research Program of the NIH, NIAID, and NIAMS. Baricitinib was provided by Eli Lilly and Company, which is the sponsor of the expanded access program for this drug.
dc.relation.isversionof10.1172/JCI98814
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleJak1/2 Inhibition with Baricitinib in the Treatment of Autoinflammatory Interferonopathies
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalThe Journal of Clinical Investigation
dc.contributor.departmentÇocuk Sağlığı ve Hastalıkları
dc.identifier.volume128
dc.identifier.issue7
dc.identifier.startpage3041
dc.identifier.endpage3052
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus


Bu öğenin dosyaları:

Bu öğe aşağıdaki koleksiyon(lar)da görünmektedir.

Basit öğe kaydını göster