Janus kinase (JAK) inhibitors
JAK inhibitors are increasingly used under specialist management in people with refractory AOSD, although this depends on local expertise. There is as yet limited evidence for their efficacy with trials currently planned or underway.[4]Macovei LA, Burlui A, Bratoiu I, et al. Adult-onset Still's disease-a complex disease, a challenging treatment. Int J Mol Sci. 2022 Oct 24;23(21):12810.
https://www.doi.org/10.3390/ijms232112810
http://www.ncbi.nlm.nih.gov/pubmed/36361602?tool=bestpractice.com
[73]Galozzi P, Bindoli S, Doria A, et al. Progress in biological therapies for adult-onset Still's disease. Biologics. 2022;16:21-34.
https://www.doi.org/10.2147/BTT.S290329
http://www.ncbi.nlm.nih.gov/pubmed/35481241?tool=bestpractice.com
In one observational study of 14 patients with refractory AOSD, tofacitinib achieved complete remission in 50% and significantly reduced the average daily dose of corticosteroid required.[95]Hu Q, Wang M, Jia J, et al. Tofacitinib in refractory adult-onset Still's disease: 14 cases from a single centre in China. Ann Rheum Dis. 2020 Jun;79(6):842-4.
https://www.doi.org/10.1136/annrheumdis-2019-216699
http://www.ncbi.nlm.nih.gov/pubmed/32079571?tool=bestpractice.com
Baricitinib has been found to induce clinical remission in patients with AOSD who had been refractory to interleukin (IL)-1 and IL-6 inhibitors.[96]Kacar M, Fitton J, Gough AK, et al. Mixed results with baricitinib in biological-resistant adult-onset Still's disease and undifferentiated systemic autoinflammatory disease. RMD Open. 2020 Jul;6(2):e001246.
https://www.doi.org/10.1136/rmdopen-2020-001246
http://www.ncbi.nlm.nih.gov/pubmed/32669454?tool=bestpractice.com
JAK inhibitors are associated with an increased risk of malignancy, major cardiovascular events, venous thromboembolism, infections, and mortality.[97]US Food and Drug Administration. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots and death for JAK inhibitors that treat certain chronic inflammatory conditions. 2021 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death
[98]European Medicines Agency. EMA confirms measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders. 2023 [internet publication].
https://www.ema.europa.eu/en/medicines/human/referrals/janus-kinase-inhibitors-jaki
[99]Medicines and Healthcare Products Regulatory Agency. Janus kinase (JAK) inhibitors: new measures to reduce risks of major cardiovascular events, malignancy, venous thromboembolism, serious infections and increased mortality. 2023 [internet publication].
https://www.gov.uk/drug-safety-update/janus-kinase-jak-inhibitors-new-measures-to-reduce-risks-of-major-cardiovascular-events-malignancy-venous-thromboembolism-serious-infections-and-increased-mortality
Interleukin (IL)-18 inhibitors
IL-18 inhibitors such as tadekinig alfa (a recombinant IL-18 binding protein with a high affinity for IL-18) have been found to have a favourable safety profile and produced a positive response in 50% of participants in a phase 2 trial.[100]Gabay C, Fautrel B, Rech J, et al. Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's disease. Ann Rheum Dis. 2018 Jun;77(6):840-7.
https://www.doi.org/10.1136/annrheumdis-2017-212608
http://www.ncbi.nlm.nih.gov/pubmed/29472362?tool=bestpractice.com
There is as yet limited evidence for their efficacy with trials currently planned or underway.[4]Macovei LA, Burlui A, Bratoiu I, et al. Adult-onset Still's disease-a complex disease, a challenging treatment. Int J Mol Sci. 2022 Oct 24;23(21):12810.
https://www.doi.org/10.3390/ijms232112810
http://www.ncbi.nlm.nih.gov/pubmed/36361602?tool=bestpractice.com
[73]Galozzi P, Bindoli S, Doria A, et al. Progress in biological therapies for adult-onset Still's disease. Biologics. 2022;16:21-34.
https://www.doi.org/10.2147/BTT.S290329
http://www.ncbi.nlm.nih.gov/pubmed/35481241?tool=bestpractice.com
Rituximab
Rituximab, an anti-CD20 monoclonal antibody, has been shown in a few case studies to have potential effectiveness for refractory AOSD. It blocks T-cell activation and the generation of pro-inflammatory cytokines.[4]Macovei LA, Burlui A, Bratoiu I, et al. Adult-onset Still's disease-a complex disease, a challenging treatment. Int J Mol Sci. 2022 Oct 24;23(21):12810.
https://www.doi.org/10.3390/ijms232112810
http://www.ncbi.nlm.nih.gov/pubmed/36361602?tool=bestpractice.com