Tofacitinib y otros inhibidores de las cinasas en el tratamiento de la psoriasis

Ortiz-Ibáñez, K.; Alsina, M.; Muñoz‐Santos, Carlos

doi:10.1016/j.ad.2012.10.018

Cited by 26 publications

(2 citation statements)

References 24 publications

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“…Indolocarbazoles, the predominate metabolites within the fused indole series, are actinomycete-dervived alkaloids which inhibit topoisomerase I and kinases relevant to anticancer, antitubercular, antimalarial and antiviral lead development. 537-540 While many indolocarbazole analogs have been discovered or synthesized, 537,538 it is noteworthy that those that have advanced furthest clinically are either a known natural product (CT327, a pegylated formulation of the natural product K252a currently in phase IIb for treating psoriasis) 541 or subtle variations thereof including N-acylated staurosporine [midostaurin/PKC412, which recently completed a successful phase II trial for acute myeloid leukemia (AML) and is currently in phase II evaluation for metastatic melanoma], 542 the N-alkylated rebeccamycin (becatecarin) 543,544 and a reduced K252a (lestauritinib/CEP-701 currently in clinical phase II/III evaluation for treating FLT3-ITD AML). 545 Indolocarbazoles are characterized by their indolo[2,3-a]pyrrolo [3,4-c]carbazole core and generally divided into two separate sub-classes exemplified by rebeccamycin 546 and staurosporine 547 with 64 glycosides cumulatively reported to date (Fig.…”

Section: Fused Indolesmentioning

confidence: 99%

A comprehensive review of glycosylated bacterial natural products

et al. 2015

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A systematic analysis of all naturally-occurring glycosylated bacterial secondary metabolites reported in the scientific literature up through early 2013 is presented. This comprehensive analysis of 15 940 bacterial natural products revealed 3426 glycosides containing 344 distinct appended carbohydrates and highlights a range of unique opportunities for future biosynthetic study and glycodiversification efforts.

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Section: Fused Indolesmentioning

confidence: 99%

A comprehensive review of glycosylated bacterial natural products

et al. 2015

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“…Therefore, these kinases have a fundamental role in cell proliferation and inflammation. Tofacitinib inhibits JAK 1 and 3, attenuating the transduction signals activated by interleukins (IL2, 4, 6, 7, 9, 15 and 21) and interferons type I and II, thereby modulating immune and inflammatory responses . In recent clinical trials, orally administered tofacitinib effectively improved clinical parameters in adult patients with moderate‐to‐severe RA either alone or in combination with other conventional DMARDs …”

Section: What Is Known and Objective; Methods; Results And Discussionmentioning

confidence: 99%

Network meta‐analysis of tofacitinib versus biologic treatments in moderate‐to‐severe rheumatoid arthritis patients

et al. 2019

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What is known and objective Rheumatoid arthritis (RA) is an autoimmune disease characterized primarily by inflammation and pain in the joints. Tofacitinib is an oral drug recently approved for RA treatment; it inhibits Janus protein kinases (JAK) that reduces RA symptoms when conventional DMARDs do not trigger a response. This study aimed to compare the efficacy of biological DMARDs in monotherapy or combined with methotrexate in RA patients and compare the treatments. Methods We reviewed the literature for articles published up to June 2017, evaluating the efficacy and safety of the biological DMARDs indicated for RA in patients with inadequate responses to conventional DMARDs and naïve to biological DMARDs, in similar populations, considering ACR50 as the efficacy variable. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each drug combination, and these parameters were transformed into differences in responses to assess the effectiveness of the alternative medicines. Equivalence therapeutic alternatives (ETA) were ensured to assess the possibility of considering these medications with equivalent efficacy. A network meta‐analysis (NMA) was performed using Bayesian approaches and the fixed‐effects model. Results and discussion Twenty‐seven randomized clinical trials (RCTs) that met the pre‐established criteria were identified. The 95% CI of biological DMARDs was higher than that of placebo without methotrexate, except for certolizumab, golimumab‐m, anakinra‐m and adalimumab monotherapy. These DMARDs performed significantly better than the placebo, except for etanercept, certolizumab, tofacitinib and golimumab. Certolizumab‐m was better than anakinra‐m and adalimumab, and tocilizumab alone or combined with methotrexate was superior to adalimumab. Etanercept‐m yielded a higher difference in responses compared with the other biological DMARDs, which presented more homogeneous responses, except for adalimumab and anakinra‐m, which yielded worse results. None of the biological DMARDs displayed ETA to etanercept‐m; however, they displayed ETA with certolizumab‐m, except for adalimumab and anakinra‐m. What is new and conclusion All biological DMARDs used in combination with methotrexate, except for etanercept, anakinra, certolizumab and tocilizumab without methotrexate, were displayed ETA on using ACR50 at week 24 in patients naïve to biological DMARDs. Etanercept displayed a greater difference in responses, although the high uncertainty of the comparative results prevented the confirmation of the increased efficacy of this drug.

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Small Molecules in the Treatment of Psoriasis

Torres

Filipe

2015

Drug Development Research

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Preclinical Research Psoriasis is an inflammatory systemic skin disease that affects various parts of the body requiring long-term management due to its chronic nature. Available treatment options include topical, systemic or biological therapies, which have long-term limitations associated to toxicity, tolerability and risk for adverse effects requiring its intermittent use and close monitoring. Small molecules modulate proinflammatory cytokines, selectively inhibit signaling pathways and showing potential to treat inflammatory diseases in patients not responding to conventional treatments. Presently, small molecules available are phosphodiesterase 4 inhibitors or Janus kinase inhibitors. Other small molecules under development for psoriasis include fumaric acid esters, amygdalin analogs, protein kinase C inhibitors, mitogen-activated protein kinase inhibitors, spleen protein kinase inhibitors, other tyrosine kinase inhibitors, sphingosine 1-phosphate receptor agonists, and A3 adenosine receptor agonists. These new treatment options represent important advances in the development of specific drugs to respond to the goals of treatment and improve patient quality of life.

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Tofacitinib y otros inhibidores de las cinasas en el tratamiento de la psoriasis

Cited by 26 publications

References 24 publications

A comprehensive review of glycosylated bacterial natural products

A comprehensive review of glycosylated bacterial natural products

Network meta‐analysis of tofacitinib versus biologic treatments in moderate‐to‐severe rheumatoid arthritis patients

Small Molecules in the Treatment of Psoriasis

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