Tofacitinib for the treatment of active ankylosing spondylitis in adults

Mohanakrishnan, Raagav; Beier, Secia; Deodhar, Atul

doi:10.1080/1744666x.2022.2038134

Cited by 16 publications

(8 citation statements)

References 25 publications

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“…Tofacitinib was initially tried to prevent allograft rejection but was later abandoned due to high dosage and excessive immunosuppression ( Webber and Vincenti, 2016 ; Coricello et al, 2020 ). In 2012, tofacitinib got FDA approval for rheumatoid arthritis; since then, it has gained regulatory approval for four other indications, including adult and juvenile psoriatic arthritis (2017), ulcerative colitis (2018), polyarticular-juvenile idiopathic arthritis (2020), and ankylosing spondylitis (2021) ( Caporali and Zavaglia, 2019 ; Mohanakrishnan et al, 2022 ; Shawky et al, 2022 ).…”

Section: Jakinibs and Covid-19mentioning

confidence: 99%

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review

et al. 2023

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Severe cases of COVID-19 are characterized by hyperinflammation induced by cytokine storm, ARDS leading to multiorgan failure and death. JAK-STAT signaling has been implicated in immunopathogenesis of COVID-19 infection under different stages such as viral entry, escaping innate immunity, replication, and subsequent inflammatory processes. Prompted by this fact and prior utilization as an immunomodulatory agent for several autoimmune, allergic, and inflammatory conditions, Jakinibs have been recognized as validated small molecules targeting the rapid release of proinflammatory cytokines, primarily IL-6, and GM-CSF. Various clinical trials are under investigation to evaluate Jakinibs as potential candidates for treating COVID-19. Till date, there is only one small molecule Jakinib known as baricitinib has received FDA-approval as a standalone immunomodulatory agent in treating critical COVID-19 patients. Though various meta-analyses have confirmed and validated the safety and efficacy of Jakinibs, further studies are required to understand the elaborated pathogenesis of COVID-19, duration of Jakinib treatment, and assess the combination therapeutic strategies. In this review, we highlighted JAK-STAT signalling in the pathogenesis of COVID-19 and clinically approved Jakinibs. Moreover, this review described substantially the promising use of Jakinibs and discussed their limitations in the context of COVID-19 therapy. Hence, this review article provides a concise, yet significant insight into the therapeutic implications of Jakinibs as potential anti-COVID agents which opens up a new horizon in the treatment of COVID-19, effectively.

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Section: Jakinibs and Covid-19mentioning

confidence: 99%

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review

et al. 2023

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“…Future promising novel therapeutic possibilities include Janus Kinases inhibitors (JAKinibs) which interrupt the JAK/STAT transduction of IL-23/IL-17 and other cytokine signals. A broad spectrum JAKinib, tofacitinib, has been approved for the treatment of rheumatoid arthritis, psoriasis, ulcerative colitis and more recently AS in patients with poor response to TNFi [ 89 , 90 ]. Phase II & III trials for tofacitinib in AS suggest the molecule attenuates zygapophyseal inflammation on MRI, a key indicator for disease progression [ 89 , 91 ].…”

Section: Advances In As Therapiesmentioning

confidence: 99%

“…A broad spectrum JAKinib, tofacitinib, has been approved for the treatment of rheumatoid arthritis, psoriasis, ulcerative colitis and more recently AS in patients with poor response to TNFi [ 89 , 90 ]. Phase II & III trials for tofacitinib in AS suggest the molecule attenuates zygapophyseal inflammation on MRI, a key indicator for disease progression [ 89 , 91 ]. Several other JAKinibs that could potentially be repurposed include ruxolitinib and baricitinib, which have recently been approved for the treatment of primary myelofibrosis and essential thrombocythaemia.…”

Section: Advances In As Therapiesmentioning

confidence: 99%

The genetic backbone of ankylosing spondylitis: how knowledge of genetic susceptibility informs our understanding and management of disease

et al. 2022

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Ankylosing spondylitis (AS) is a seronegative, chronic inflammatory arthritis with high genetic burden. A strong association with HLA-B27 has long been established, but to date its contribution to disease aetiology remains unresolved. Recent insights through genome wide studies reveal an increasing array of immunogenetic risk variants extraneous to the HLA complex in AS cohorts. These genetic traits build a complex profile of disease causality, highlighting several molecular pathways associated with the condition. This and other evidence strongly implicates T-cell-driven pathology, revolving around the T helper 17 cell subset as an important contributor to disease. This prominence of the T helper 17 cell subset has presented the opportunity for therapeutic intervention through inhibition of interleukins 17 and 23 which drive T helper 17 activity. While targeting of interleukin 17 has proven effective, this success has not been replicated with interleukin 23 inhibition in AS patients. Evidence points to significant genetic diversity between AS patients which may, in part, explain the observed refractoriness among a proportion of patients. In this review we discuss the impact of genetics on our understanding of AS and its relationship with closely linked pathologies. We further explore how genetics can be used in the development of therapeutics and as a tool to assist in the diagnosis and management of patients. This evidence indicates that genetic profiling should play a role in the clinician’s choice of therapy as part of a precision medicine strategy towards disease management.

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“…In addition, tofacitinib has received FDA approval for the treatment of juvenile idiopathic arthritis in 2020 [ 179 ]. In December 2021, tofacitinib was approved for the treatment of active ankylosing spondylitis [ 180 ].…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Overview of Globally Approved JAK Inhibitors

et al. 2022

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Janus kinase (JAK) is a family of cytoplasmic non-receptor tyrosine kinases that includes four members, namely JAK1, JAK2, JAK3, and TYK2. The JAKs transduce cytokine signaling through the JAK-STAT pathway, which regulates the transcription of several genes involved in inflammatory, immune, and cancer conditions. Targeting the JAK family kinases with small-molecule inhibitors has proved to be effective in the treatment of different types of diseases. In the current review, eleven of the JAK inhibitors that received approval for clinical use have been discussed. These drugs are abrocitinib, baricitinib, delgocitinib, fedratinib, filgotinib, oclacitinib, pacritinib, peficitinib, ruxolitinib, tofacitinib, and upadacitinib. The aim of the current review was to provide an integrated overview of the chemical and pharmacological data of the globally approved JAK inhibitors. The synthetic routes of the eleven drugs were described. In addition, their inhibitory activities against different kinases and their pharmacological uses have also been explained. Moreover, their crystal structures with different kinases were summarized, with a primary focus on their binding modes and interactions. The proposed metabolic pathways and metabolites of these drugs were also illustrated. To sum up, the data in the current review could help in the design of new JAK inhibitors with potential therapeutic benefits in inflammatory and autoimmune diseases.

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Tofacitinib for the treatment of active ankylosing spondylitis in adults

Cited by 16 publications

References 25 publications

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review

The genetic backbone of ankylosing spondylitis: how knowledge of genetic susceptibility informs our understanding and management of disease

A Comprehensive Overview of Globally Approved JAK Inhibitors

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