JAK inhibitors in 2019, synthetic review in 10 points

Müller, R.

doi:10.1016/j.ejim.2019.05.022

Cited by 31 publications

(26 citation statements)

References 64 publications

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“…Small molecule therapy is relatively new treatment so their position in therapeutic hierarchy is not strongly placed. In RA treatment, the most recent EULAR recommendations from 2016 [ 82 ] placed JAKi in the second line, after failure of a first line csDMARDs (particularly MTX) and presence of unfavorable prognostic factors [ 83 ]. The ACR recommendations from 2015, which are more strict, assaulted the use of JAKi as the third choice treatment, in case of failure of csDMARDs or TNFi plus MTX or non-TNFi biologic (abatacept, rituximab, tocilizumab) plus MTX [ 5 ].…”

Section: Tsdmards Based On Jaks/mapks/nf-κb/syk-btk-targeted Theramentioning

confidence: 99%

Small Molecule Inhibitors in the Treatment of Rheumatoid Arthritis and Beyond: Latest Updates and Potential Strategy for Fighting COVID-19

Massalska

Maśliński

Ciechomska

2020

Cells

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The development of biological disease-modifying antirheumatic drugs (bDMARDs) and target synthetic DMARDs (tsDMARDs), also known as small molecule inhibitors, represent a breakthrough in rheumatoid arthritis (RA) treatment. The tsDMARDs are a large family of small molecules targeting mostly the several types of kinases, which are essential in downstream signaling of pro-inflammatory molecules. This review highlights current challenges associated with the treatment of RA using small molecule inhibitors targeting intracellular JAKs/MAPKs/NF-κB/SYK-BTK signaling pathways. Indeed, we have provided the latest update on development of small molecule inhibitors, their clinical efficacy and safety as a strategy for RA treatment. On the other hand, we have highlighted the risk and adverse effects of tsDMARDs administration including, among others, infections and thromboembolism. Therefore, performance of blood tests or viral infection screening should be recommended before the tsDMARDs administration. Interestingly, recent events of SARS-CoV-2 outbreak have demonstrated the potential use of small molecule inhibitors not only in RA treatment, but also in fighting COVID-19 via blocking the viral entry, preventing of hyperimmune activation and reducing cytokine storm. Thus, small molecule inhibitors, targeting wide range of pro-inflammatory singling pathways, may find wider implications not only for the management of RA but also in the controlling of COVID-19.

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Section: Tsdmards Based On Jaks/mapks/nf-κb/syk-btk-targeted Theramentioning

confidence: 99%

Small Molecule Inhibitors in the Treatment of Rheumatoid Arthritis and Beyond: Latest Updates and Potential Strategy for Fighting COVID-19

Massalska

Maśliński

Ciechomska

2020

Cells

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“…Lipide/kardiovaskuläres Risiko Gespoolte Studiendaten, die sich auf Veränderungen von Lipiden fokussierten, zeigen, dass unter Therapie mit Tofacitinib und Baricitinib erhöhte Serumspiegel von Gesamtcholesterin, LDL und HDL-Cholesterin auftreten [5][6][7][8]. Diese Erhöhungen scheinen nicht nur durch die Korrektur der durch die Entzündung verursachten niedrigen Lipid-Spiegel bedingt zu sein, da sie häufiger und in höherem Maße als bei vergleichbaren antiinflammatorischen Therapien wie TNF-Inhibitoren beobachtet werden [9]. Entscheidend ist jedoch in diesem Zusammenhang, dass die LDL/HDL-Ratio unverändert bleibt, was auf eine geringe Auswirkung auf das kardiovaskuläre Risiko hinweist [9].…”

Section: Sicherheit -Nicht Infektiöse Nebenwirkungenunclassified

“…Diese Erhöhungen scheinen nicht nur durch die Korrektur der durch die Entzündung verursachten niedrigen Lipid-Spiegel bedingt zu sein, da sie häufiger und in höherem Maße als bei vergleichbaren antiinflammatorischen Therapien wie TNF-Inhibitoren beobachtet werden [9]. Entscheidend ist jedoch in diesem Zusammenhang, dass die LDL/HDL-Ratio unverändert bleibt, was auf eine geringe Auswirkung auf das kardiovaskuläre Risiko hinweist [9]. Tatsächlich ergaben die bisher durchgeführten Analysen kein erhöhtes kardiovaskuläres Risiko [7,10,11].…”

Section: Sicherheit -Nicht Infektiöse Nebenwirkungenunclassified

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Sicherheit von JAK-Inhibitoren

Leipe¹

2019

Arthritis und Rheuma

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ZusammenfassungDie zugelassenen Januskinase (JAK)-Inhibitoren Baricitinib und Tofacitinib haben bereits das Armamentarium hochwirksamer Therapien bei rheumatoider Arthritis, Psoriasis-Arthritis und Colitis ulcerosa erweitert. Als Alternative zu Biologika unterscheiden sie sich jedoch durch den Wirkmechanismus (Hemmung intrazellulärer Signalübertragung) und die orale Verfügbarkeit. Die Sicherheit ist jedoch ähnlich gut wie bei Biologika, am häufigsten kommen leichtgradige Infekte der oberen Atemwege vor. Verhältnismäßig seltene, aber spezifische Nebenwirkungen stellen Herpes-Zoster-Infektionen dar. Schwere Infektionen werden nur selten beobachtet. Nicht-infektiöse Nebenwirkungen beinhalten Laborwertveränderungen in Form von Zytopenien, Anstieg von Cholesterin (scheinbar ohne Erhöhung des kardiovaskulären Risikos), selten Leber- und Nierenwert-Erhöhungen sowie vermutlich ein erhöhtes Thromboembolie-Risiko bei bestimmten Risikokonstellationen.

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“…JAK inhibitors have a lower production cost compared to monoclonal antibodies, and a higher production cost compared to corticosteroids. 29,64,65 JAK inhibitors may be administered orally or topically, allowing for convenient routes of administration. 6 As the testing of JAK inhibitors as therapies for AD continues, it will be important for longer-term trials to achieve a better understanding of any time-related AE and efficacy concerns, as this information is currently largely unavailable given the recent development of many of these agents.…”

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confidence: 99%

<p>Emerging Role of Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis</p>

Singh¹,

Heron²,

Ghamrawi³

et al. 2020

ITT

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Background Atopic dermatitis (AD) is a common chronic, inflammatory skin condition. The pathogenesis of AD involves many cytokines that utilize the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling cascade; therefore, JAK inhibitors may be used in the treatment of AD. This review aims to evaluate the pathophysiology, efficacy, and safety of JAK inhibitors and their emerging role as a therapeutic option for patients with AD. Methods A PubMed search of Phase I, II, and III clinical trials was conducted for relevant literature published between January 2015 and June 2020 utilizing the key terms: JAK inhibitors, atopic dermatitis, efficacy, safety, and treatment. The search was subsequently expanded to include additional terms. Results In multiple Phase II and III clinical trials, JAK inhibitors were more efficacious than placebo or vehicle controls and slightly more efficacious in direct comparisons to corticosteroids. Overall, JAK inhibitors have a moderate safety profile for use in AD. Some of the more severe theoretical adverse events included thrombosis and reactivation of viral infections. While data remain limited for the long-term efficacy and safety of JAK inhibitor use in patients with AD, many ongoing clinical trials have promising preliminary results. Discussion Short-term data suggest that both topical and oral JAK inhibitors are efficacious and safe for use in patients with AD, although cases of thrombosis and viral disease have been reported. While the current standard treatments for AD are likely preferred, failed therapy with these agents or corticosteroid phobia may be indications for the use of JAK inhibitors in patients with AD.

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JAK inhibitors in 2019, synthetic review in 10 points

Cited by 31 publications

References 64 publications

Small Molecule Inhibitors in the Treatment of Rheumatoid Arthritis and Beyond: Latest Updates and Potential Strategy for Fighting COVID-19

Small Molecule Inhibitors in the Treatment of Rheumatoid Arthritis and Beyond: Latest Updates and Potential Strategy for Fighting COVID-19

Sicherheit von JAK-Inhibitoren

<p>Emerging Role of Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis</p>

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