A Case Series on Patients on Tofacitinib in Combination With a Biologic

Barroso, Nashla; Miller, Elizabeth Z.; Fürst, Daniel E.

doi:10.1097/rhu.0000000000000663

Cited by 21 publications

(13 citation statements)

References 13 publications

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“…For many disorders, from cancer to autoimmunity, combination chemotherapy is required for effective therapy and remission. Jakinibs can be safely used with MTX, but they are also being used with biologics [108]. The safety and efficacy of this strategy will need to be established.…”

Section: Next-generation Selective Jakinibsmentioning

confidence: 99%

Janus kinases to jakinibs: from basic insights to clinical practice

et al. 2019

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Cytokines are critical mediators of diverse immune and inflammatory diseases. Targeting cytokines and cytokine receptors with biologics has revolutionized the treatment of many of these diseases, but targeting intracellular signalling with Janus kinase (JAK) inhibitors (jakinibs) now represents a major new therapeutic advance. We are still in the first decade since these drugs were approved and there is still much to be learned about the mechanisms of action of these drugs and the practical use of these agents. Herein we will review cytokines that do, and just as importantly, do not signal by JAKs, as well as explain how this relates to both efficacy and side effects in various diseases. We will review new, next-generation selective jakinibs, as well as the prospects and challenges ahead in targeting JAKs.

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Section: Next-generation Selective Jakinibsmentioning

confidence: 99%

Janus kinases to jakinibs: from basic insights to clinical practice

et al. 2019

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“…For many disorders from cancer to autoimmunity, a combination chemotherapy is required for effective therapy and remission. Jakinibs can be safely used with methotrexate, but they are also being used with biologics; the safety and efficacy of this strategy will need to be established. We now appreciate the complexity of regulation of key genes such as those encoding pro‐inflammatory cytokines and their receptors; such highly regulated genes reside within loci with super‐enhancer architecture.…”

Section: What's Aheadmentioning

confidence: 99%

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs

Gadina

Johnson

Schwartz

et al. 2018

Journal of Leukocyte Biology

130

100

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In this era, it is axiomatic that cytokines have critical roles in cellular development and differentiation, immune homeostasis, and host defense. Equally, dysregulation of cytokines is known to contribute to diverse inflammatory and immune-mediated disorders. In fact, the past 20 years have witnessed the rapid translation of basic discoveries in cytokine biology to multiple successful biological agents (mAbs and recombinant fusion proteins) that target cytokines. These targeted therapies have not only fundamentally changed the face of multiple immune-mediated diseases but have also unequivocally established the role of specific cytokines in human disease; cytokine biologists have many times over provided remarkable basic advances with direct clinical benefit. Numerous cytokines rely on the JAK-STAT pathway for signaling, and new, safe, and effective small molecule inhibitors have been developed for a range of disorders. In this review, we will briefly summarize basic discoveries in cytokine signaling and briefly comment on some major unresolved issues. We will review clinical data pertaining to the first generation of JAK inhibitors and their clinical indications, discuss additional opportunities for targeting this pathway, and lay out some of the challenges that lie ahead.

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“…Similarly, the risks and benefits of jakinibs as monotherapy vs. combination therapy with other immunomodulators such as MTX or even biologics 197 remain incompletely characterized. As the renal transplant studies have shown, this strategy is not without risk, but could potentially be managed using a serum concentration-based dose escalation protocol or immunological functional studies to gauge early response to therapy.…”

Section: Future Directionsmentioning

confidence: 99%

Erratum: JAK inhibition as a therapeutic strategy for immune and inflammatory diseases

Schwartz¹,

Kanno²,

Villarino³

et al. 2018

Nat Rev Drug Discov

293

109

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Proof provided by biological therapies that cytokines are truly key drivers of immune-mediated diseases has spurred effort in targeting their associated signaling pathways. Small-molecule drugs that inhibit Janus kinases (jakinibs), which are essential signaling mediators downstream of many pro-inflammatory cytokines, have gained traction as safe and efficacious options for the treatment of inflammation-driven pathologies like rheumatoid arthritis, psoriasis and inflammatory bowel disease. Building on the clinical success of first-generation jakinibs, second-generation compounds which claim greater selectivity are currently undergoing development and proceeding to clinical trials. However, important questions remain about the advantages and limitations of improved JAK selectivity, optimal routes and dosing regimens, and how best to identify patients that will benefit from jakinibs. This review will discuss the biology of jakinibs from a translational perspective, focusing on recent insights from clinical trials, the development of novel agents, and the use of jakinibs in a spectrum of immune and inflammatory diseases.

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A Case Series on Patients on Tofacitinib in Combination With a Biologic

Cited by 21 publications

References 13 publications

Janus kinases to jakinibs: from basic insights to clinical practice

Janus kinases to jakinibs: from basic insights to clinical practice

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs

Erratum: JAK inhibition as a therapeutic strategy for immune and inflammatory diseases

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