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Efficacy and safety of dose escalation of tofacitinib in refractory anti-MDA5 antibody-positive dermatomyositis

Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is frequently complicated with rapidly progressive-interstitial lung disease (RP-ILD). The prognosis of MDA5-DM with RP-ILD is mostly poor despite intensive treatment with a combination of high-dose...

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Autores principales: Ida, Tomoaki, Furuta, Shunsuke, Takayama, Asuka, Tamura, Jun, Hayashi, Yuki, Abe, Kazuya, Kurihara, Syunjiro, Ishikawa, Junichi, Iwamoto, Taro, Ikeda, Kei, Suzuki, Kotaro, Nakajima, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9809321/
https://www.ncbi.nlm.nih.gov/pubmed/36593080
http://dx.doi.org/10.1136/rmdopen-2022-002795
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author Ida, Tomoaki
Furuta, Shunsuke
Takayama, Asuka
Tamura, Jun
Hayashi, Yuki
Abe, Kazuya
Kurihara, Syunjiro
Ishikawa, Junichi
Iwamoto, Taro
Ikeda, Kei
Suzuki, Kotaro
Nakajima, Hiroshi
author_facet Ida, Tomoaki
Furuta, Shunsuke
Takayama, Asuka
Tamura, Jun
Hayashi, Yuki
Abe, Kazuya
Kurihara, Syunjiro
Ishikawa, Junichi
Iwamoto, Taro
Ikeda, Kei
Suzuki, Kotaro
Nakajima, Hiroshi
author_sort Ida, Tomoaki
collection PubMed
description Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is frequently complicated with rapidly progressive-interstitial lung disease (RP-ILD). The prognosis of MDA5-DM with RP-ILD is mostly poor despite intensive treatment with a combination of high-dose glucocorticoids and single conventional immunosuppressants. It was reported that the triple therapy (high-dose glucocorticoids, cyclophosphamide and tacrolimus) was more effective than a combination of high-dose glucocorticoids and stepwise addition of immunosuppressants. In addition, the efficacy of tofacitinib 10 mg/day for MDA5-DM with RP-ILD refractory to the triple therapy was suggested. However, the effect of those therapies was evaluated only in comparison to the historical control. Moreover, more importantly, there are still refractory patients even if treated with those therapies. In this case series, we report six MDA5-DM cases with RP-ILD in which the dose of tofacitinib was increased from 10 mg to 20 mg/day due to poor response to the triple therapy, followed by tofacitinib 10 mg/day. Four of six patients improved after dose escalation of tofacitinib, while two non-responders died. All six patients developed at least one infection including five cases of cytomegalovirus reactivation, one pulmonary aspergillosis, one herpes zoster and one herpes simplex keratitis. These cases suggest that the dose escalation of tofacitinib can be an option for MDA5-DM patients refractory to 10 mg/day of tofacitinib and other immunosuppressants although the risk of infection is a concern. The risk–benefit balance of the dose escalation of tofacitinib should be carefully assessed in each case.
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spelling pubmed-98093212023-01-04 Efficacy and safety of dose escalation of tofacitinib in refractory anti-MDA5 antibody-positive dermatomyositis Ida, Tomoaki Furuta, Shunsuke Takayama, Asuka Tamura, Jun Hayashi, Yuki Abe, Kazuya Kurihara, Syunjiro Ishikawa, Junichi Iwamoto, Taro Ikeda, Kei Suzuki, Kotaro Nakajima, Hiroshi RMD Open Connective Tissue Diseases Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is frequently complicated with rapidly progressive-interstitial lung disease (RP-ILD). The prognosis of MDA5-DM with RP-ILD is mostly poor despite intensive treatment with a combination of high-dose glucocorticoids and single conventional immunosuppressants. It was reported that the triple therapy (high-dose glucocorticoids, cyclophosphamide and tacrolimus) was more effective than a combination of high-dose glucocorticoids and stepwise addition of immunosuppressants. In addition, the efficacy of tofacitinib 10 mg/day for MDA5-DM with RP-ILD refractory to the triple therapy was suggested. However, the effect of those therapies was evaluated only in comparison to the historical control. Moreover, more importantly, there are still refractory patients even if treated with those therapies. In this case series, we report six MDA5-DM cases with RP-ILD in which the dose of tofacitinib was increased from 10 mg to 20 mg/day due to poor response to the triple therapy, followed by tofacitinib 10 mg/day. Four of six patients improved after dose escalation of tofacitinib, while two non-responders died. All six patients developed at least one infection including five cases of cytomegalovirus reactivation, one pulmonary aspergillosis, one herpes zoster and one herpes simplex keratitis. These cases suggest that the dose escalation of tofacitinib can be an option for MDA5-DM patients refractory to 10 mg/day of tofacitinib and other immunosuppressants although the risk of infection is a concern. The risk–benefit balance of the dose escalation of tofacitinib should be carefully assessed in each case. BMJ Publishing Group 2023-01-02 /pmc/articles/PMC9809321/ /pubmed/36593080 http://dx.doi.org/10.1136/rmdopen-2022-002795 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Connective Tissue Diseases
Ida, Tomoaki
Furuta, Shunsuke
Takayama, Asuka
Tamura, Jun
Hayashi, Yuki
Abe, Kazuya
Kurihara, Syunjiro
Ishikawa, Junichi
Iwamoto, Taro
Ikeda, Kei
Suzuki, Kotaro
Nakajima, Hiroshi
Efficacy and safety of dose escalation of tofacitinib in refractory anti-MDA5 antibody-positive dermatomyositis
title Efficacy and safety of dose escalation of tofacitinib in refractory anti-MDA5 antibody-positive dermatomyositis
title_full Efficacy and safety of dose escalation of tofacitinib in refractory anti-MDA5 antibody-positive dermatomyositis
title_fullStr Efficacy and safety of dose escalation of tofacitinib in refractory anti-MDA5 antibody-positive dermatomyositis
title_full_unstemmed Efficacy and safety of dose escalation of tofacitinib in refractory anti-MDA5 antibody-positive dermatomyositis
title_short Efficacy and safety of dose escalation of tofacitinib in refractory anti-MDA5 antibody-positive dermatomyositis
title_sort efficacy and safety of dose escalation of tofacitinib in refractory anti-mda5 antibody-positive dermatomyositis
topic Connective Tissue Diseases
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9809321/
https://www.ncbi.nlm.nih.gov/pubmed/36593080
http://dx.doi.org/10.1136/rmdopen-2022-002795
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