scholarly journals Update on the therapeutic management of patients with either psoriatic arthritis or ulcerative colitis: focus on the JAK inhibitor tofacitinib

2021 ◽  
Vol 13 ◽  
pp. 1759720X2097777
Author(s):  
Maria Sole Chimenti ◽  
Paola Conigliaro ◽  
Livia Biancone ◽  
Roberto Perricone
Keyword(s):  
Ulcerative Colitis ◽  
Psoriatic Arthritis ◽  
Janus Kinase ◽  
Phase Iii ◽  
Jak Inhibitors ◽  
Immune Mediated ◽  
Significant Burden ◽  
Phase Iii Trials ◽  
Disease Modifying Agents ◽  
Interleukin Inhibitors

Psoriatic arthritis (PsA) and ulcerative colitis (UC) are immune-mediated diseases that cause significant burden worldwide. Recent advances in their management have improved patient outcomes. However, significant unmet needs still remain as not all patients respond to current treatments, and patients may lose responsiveness over time. An improved understanding of the pathophysiology of these diseases has brought about the development of novel disease-modifying agents, including interleukin inhibitors and, more recently, Janus kinase (JAK) inhibitors. With the approval of tofacitinib for the treatment of adults with active PsA and in adult patients with moderately-to-severely active UC, JAK inhibitors have recently entered the treatment armamentarium for PsA and UC. A number of other JAK inhibitors are also undergoing clinical development and are currently in phase III trials. This review provides an overview of the current therapeutic options for PsA and UC, with a focus on the JAK inhibitors.

scholarly journals JAK Inhibitors: Treatment Efficacy and Safety Profile in Patients with Psoriasis

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Leeyen Hsu ◽  
April W. Armstrong
Keyword(s):  
Clinical Trials ◽  
Clinical Symptoms ◽  
Treatment Options ◽  
Janus Kinase ◽  
Phase Iii ◽  
Jak Inhibitors ◽  
Psoriasis Treatment ◽  
Jak2 Inhibitor ◽  
Early Phase Trials ◽  
Phase Iii Trials

Janus kinase (JAK) pathways are key mediators in the immunopathogenesis of psoriasis. Psoriasis treatment has evolved with the advent of targeted therapies, which inhibit specific components of the psoriasis proinflammatory cascade. JAK inhibitors have been studied in early phase trials for psoriasis patients, and the data are promising for these agents as potential treatment options. Tofacitinib, an oral or topically administered JAK1 and JAK3 inhibitor, and ruxolitinib, a topical JAK1 and JAK2 inhibitor, have been most extensively studied in psoriasis, and both improved clinical symptoms of psoriasis. Additional JAK1 or JAK3 inhibitors are being studied in clinical trials. In phase III trials for rheumatoid arthritis, tofacitinib was efficacious in patients with inadequate responses to tumor necrosis factor inhibitors, methotrexate monotherapy, or disease-modifying antirheumatic drugs. The results of phase III trials are pending for these therapies in psoriasis, and these agents may represent important alternatives for patients with inadequate responses to currently available agents. Further investigations with long-term clinical trials are necessary to verify their utility in psoriasis treatment and assess their safety in this patient population.

scholarly journals Efficacy of JAK inhibitors in Ulcerative Colitis

2019 ◽  
Vol 14 (Supplement_2) ◽  
pp. S737-S745 ◽  
Author(s):  
Marc Ferrante ◽  
João Sabino
Keyword(s):  
Ulcerative Colitis ◽  
Tumour Necrosis ◽  
Oral Formulation ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Efficacy Data ◽  
Novel Therapy ◽  
Severe Ulcerative Colitis ◽  
Immune Mediated ◽  
Necrosis Factor

Abstract Janus kinase [JAK] inhibitors are a completely novel therapy for the treatment of patients with immune-mediated inflammatory disorders. The oral formulation of tofacitinib has recently been approved for the treatment of moderate-to-severe ulcerative colitis. In the placebo-controlled OCTAVE programme, tofacitinib proved to be efficacious for both inducing and maintaining clinical remission, and this both in anti-tumour necrosis factor-naïve and exposed patients. Several other anti-JAK inhibitors are currently explored. This review summarises the available efficacy data from all anti-JAK inhibitors in ulcerative colitis.

scholarly journals Spleen and Symptom Responses of JAK Inhibitors in Myelofibrosis; A Systematic Review of Phase 2 and 3 Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 26-27
Author(s):  
Muhammad Ans Sharif ◽  
Muhammad Salman Faisal ◽  
Yazan Samhouri ◽  
Laila Hashim ◽  
Muhammad Yasir ◽  
...  
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Phase Ii ◽  
Janus Kinase ◽  
Phase Iii ◽  
Symptom Improvement ◽  
Jak Inhibitors ◽  
Phase Ii Trials ◽  
Phase Iii Trials ◽  
Symptom Response

Background: The JAK-STAT pathway is a vital signaling pathway for various cytokines and growth factors. An abnormal upregulation of this pathway is seen in myeloproliferative disorders, especially the classic BCR-ABL negative myelofibrosis (MF). Janus kinase inhibitors (JAKi) have been evaluated in various clinical trials regarding their efficacy in improving the outcomes for MF patients. In this review, we looked at the reduction of splenomegaly and symptom improvement as markers for efficacy of JAKi. Methods: We did a comprehensive literature search, following PRISMA guidelines, on PubMed, Cochrane, clinicaltrials.gov and Embase databases. We used MeSH terms and related keywords for MF and JAKi, including generic and trade names. We screened 3261 articles and selected 23 trials for our study. Case reports, case series, meta-analysis, review articles, observational studies, phase I trials and studies not reporting spleen response were excluded. Spleen and symptom responses were used to determine the efficacy of JAK inhibitors. Spleen volume reduction (SVR) by >35%, spleen length reduction (SLR) by >50% and total symptom score (TSS) improvement by >50% were set as benchmarks for a positive response. Results: We included 23 trials (n= 4739) in our review. There were 15 phase II trials (n=964) and 8 phase III trials (n=3775). Of these 23 trials, 7 trials (n=598) included patients with median age below 65 years, while 16 trials (n=4141) included patients of median age more than 65 years. Of the 9 of trials of ruxolitinib, 4 were phase III trials (n= 2809) and 5 were phase II trials (n= 416). The dose of ruxolitinib used in these trials ranged from 5 mg twice daily to 20 mg twice daily. The percentage of patients who achieved spleen response ranged from 15.6% to 71.7%. There were 5 trials (n= 861) that evaluated efficacy of momelotinib. Three were phase II trials (n= 221), while 2 were phase III trials (n=326). The doses ranged from 150mg to 300mg. The splenic response in patients ranged from 7% to 48%. In one phase 3 randomized control trial, efficacy of momelotinib (N=215)and roxulotinib (N=217) were compared, and were found to be equally efficacious in terms of spleen response (26.5% in the momelotinib group while 29% in the ruxolitinib group) and symptom response (28.4% in the momelotinib group and 42.2% in the ruxolitinib group). In 4 trials (n= 453) of fedratinib, there were 2 phase II trials (n= 127) and 2 phase III trials (n=326). The splenic response ranged from 31% to 73% of the patient population. In phase II JAKARTA2 study, patients who were resistant or intolerant to ruxolitinib showed SVR of 31%. Lestaurtunib, Ilgitanib, pacritinib and itacitinib were studied in 2,1,1, and 1 phase II trials, respectively. The splenic response was 75%, 31%, 31%, and 68.8% respectively. Symptom response was reported in 12 studies (N=1477). The percentage of patients who achieved symptom response receiving roxulotinib were 20.8-49%, momelotinib (28.4-30.7%), ictatinib (51.1-59.4%), practinib (48%), and fedratinib (27-36%). In terms of safety, the most common hematological side effects seen were anemia (15% - 65%), thrombocytopenia (1.3% - 64%) and neutropenia (1% - 28%). These side effects were seen equally with different medications. The most common non hematological adverse effects included diarrhea (4% - 32%), abdominal pain (2.6% - 27.1%) and fatigue (1.3% - 10%). Conclusion Splenomegaly and associated symptoms are major source of morbidity in MF patients. The rapid advancement in novel agents in the last decade changed the treatment paradigm in this disorder. Our systematic review summarizes the effect of JAKi on spleen and symptom responses. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Fazal:Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Karyopharm: Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; GlaxoSmithKline: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Janssen: Speakers Bureau.

scholarly journals AB0565 JAK INHIBITORS AND PSORIATIC ARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1319-1320
Author(s):  
F. Campanaro ◽  
A. Zaffaroni ◽  
A. Batticciotto ◽  
A. Cappelli ◽  
M. P. Donadini ◽  
...  
Keyword(s):  
Systematic Review ◽  
Psoriatic Arthritis ◽  
Response Rate ◽  
Mean Difference ◽  
Janus Kinase ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Jak Inhibitors ◽  
Acr20 Response ◽  
Acr20 Response Rate

Background:Despite the therapeutic armamentarium for the treatment of psoriatic arthritis (PsA) has considerably expanded over the last thirty years, there is a huge necessity of finding effective drugs for this disease. JAK inhibitors (JAKi) are small molecules able to interfere with the JAK/STAT pathway, involved in the pathogenesis of PsA (1). Up to now Tofacitinib is the only JAKi approved by the European Medicines Agency (EMA) for the treatment of PsA but in the next few years the number of approved JAKi is expected to rise significantly.Objectives:To assess the efficacy and safety of different JAKi for the treatment of PsA.Methods:A systematic review of the literature was performed to identify randomized controlled trials (RCTs), by electronic search of MEDLINE and EMBASE database until October 2020. Studies were considered eligible if they met the following criteria: I) study was a RCT; II) only patients with PsA were included; III) JAKi was compared to placebo in addition to the standard of care. Two reviewers (FC and AZ) performed study selection, with disagreements solved by the opinion of an expert reviewer (AS). The outcomes were expressed as odds ratio (OR) and 95% confidence intervals (95% CI). Statistical heterogeneity was assessed with the I2 statistic.Results:We identified 557 potentially relevant studies. A total of 554 studies were excluded based on title and/or abstract screening. Three RCTs for a total of 947 PsA patients treated with JAKi were included (2,3,4). Two were phase III studies on the efficacy and safety of Tofacitinib (OPAL Beyond and OPAL Broaden) and one was a phase II study on Filgotinib (Equator). All three studies were judged at low risk of bias according to Cochrane criteria (5). The primary efficacy outcome in all the studies was the number of patients who achieved the response rate of the American College of Rheumatology 20 score (ACR20). The outcomes evaluation was performed at 12 week for the Filgotinib trial and at 16 week for the Tofacitinib trials. We used for the main analyses the group of patients randomized to Tofacitinib 5 mg because this is the only dosage approved by the EMA for the treatment of PsA. JAKi showed a significantly higher ACR20 response rate compared to placebo (OR 3.54, 95% CI 1.76 - 7.09, I^2 = 74%). JAKi also showed a significantly higher ACR50 response rate (OR 3.36, 95% CI 2.22 - 5.09, I^2 = 0%), ACR70 response rate (OR 2.82, 95% CI 1.67 - 4.76, I^2 = 20%), PsARC response rate (OR 2.67, 95% CI 1.26 - 5.65, I^2 = 79%), PASI75 response rate (OR 3.15, 95% CI 1.61 - 6.15, I^2 = 45%) compared to placebo. JAKi were also associated with significantly better HAQ-DI (mean difference -0.23 95% CI -0.31 - -0.14) and fatigue, measured with FACIT-F (mean difference 3.54 95% CI 2.13 - 4.94). JAKi compared to placebo were associated with a non-statistically significant different risk of serious adverse events (OR 0.56, 95% CI 0.11 - 2.91, I^2 = 38%).Conclusion:This is the first published systematic review that performed a comprehensive and simultaneous evaluation of the efficacy and safety of JAKi for PsA in RCTs. Our analysis suggests a statistically significant benefit of JAKi, that appears to be effective and safe over placebo. The impact of these data on international clinical guidelines needs further investigation.References:[1]George E Fragoulis, et al. JAK-inhibitors. New players in the field of immune-mediated diseases, beyond rheumatoid arthritis, Rheumatology, Volume 58, Issue Supplement_1, February 2019, Pages i43–i54[2]Mease P, et al. Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N Engl J Med 2017; 377: 1537-50.[3]Gladman D, et al. Tofacitinib for psoriatic arthritis in patients with an inadequate response to TNF inhibitors. N Engl J Med 2017; 377: 1525-36.[4]Mease P, et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial. Lancet 2018;392:2367–77.[5]Higgins JP, et Al. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-560Figure 1.ACR20 response rate of Jaki over PlaceboDisclosure of Interests:None declared.

scholarly journals Tofacitinib or adalimumab versus placebo: patient-reported outcomes from OPAL Broaden—a phase III study of active psoriatic arthritis in patients with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000806 ◽  
Author(s):  
Vibeke Strand ◽  
Kurt de Vlam ◽  
Jose A Covarrubias-Cobos ◽  
Philip J Mease ◽  
Dafna D Gladman ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Patient Reported Outcomes ◽  
Short Form ◽  
Janus Kinase ◽  
Phase Iii ◽  
Placebo Patient ◽  
Pain Patient ◽  
Inadequate Response ◽  
Patient Reported ◽  
Disease Modifying

ObjectivesTofacitinib is an oral Janus kinase inhibitor for treatment of psoriatic arthritis (PsA). We evaluated patient-reported outcomes (PROs) in patients with PsA refractory to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and tumour necrosis factor inhibitor-naïve in a 12-month, phase III randomised controlled trial (OPAL Broaden [NCT01877668]).MethodsPatients (N=422) received tofacitinib 5 mg or 10 mg twice daily, adalimumab 40 mg subcutaneously every 2 weeks or placebo advancing to tofacitinib 5 mg or 10 mg twice daily at month 3. Least squares mean changes from baseline and percentages of patients reporting improvements ≥minimum clinically important differences (MCID); and scores ≥normative values in: Patient Global Assessment of disease activity (PtGA), Pain, Patient Global Joint and Skin Assessment (PGJS), Short Form-36 Health Survey version 2 (SF-36v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), EuroQol 5-Dimensions-3-level questionnaire (EQ-5D-3L) and Ankylosing Spondylitis Quality of Life (ASQoL) were determined. Nominal p values were cited without multiple comparison adjustments.ResultsAt month 3, PtGA, Pain, PGJS, FACIT-Fatigue, EQ-5D-3L, ASQoL and SF-36v2 Physical Component Summary (PCS), physical functioning (PF), bodily pain (BP) and vitality domain scores exceeded placebo with both tofacitinib doses (p≤0.05); SF-36v2 social functioning with 5 mg twice daily (p≤0.05). Percentages reporting improvements ≥MCID in PtGA, Pain, PGJS, FACIT-Fatigue, ASQoL and SF-36v2 PCS, PF, BP and general health scores exceeded placebo with both tofacitinib doses (p≤0.05) and were similar with adalimumab.ConclusioncsDMARD-IR patients with active PsA reported statistically and clinically meaningful improvements in PROs with tofacitinib compared with placebo at Month 3.

BARICITINIB: NEW PHARMACOTHERAPY OPTIONS FOR RHEUMATOID ARTHRITIS AND OTHER IMMUNE-MEDIATED INFLAMMATORY RHEUMATIC DISEASES

2020 ◽  
Vol 58 (3) ◽  
pp. 304-316
Author(s):  
E. L. Nasonov ◽  
A. M. Lila
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatic Diseases ◽  
Janus Kinase ◽  
Inflammatory Rheumatic Diseases ◽  
Jak Inhibitors ◽  
Oral Medications ◽  
Immune Mediated ◽  
Wide Range ◽  
Promising Area ◽  
Medical Advances

Deciphering the mechanisms of the pathogenesis of immune-mediated inflammatory rheumatic diseases (IMIRDs) in conjunction with designing a wide range of biological agents is one of the major medical advances in the 21st century. A new promising area of pharmacotherapy for IMIRDs is associated with the design of the so-called targeted oral medications that primarily include Janus kinase (JAK) inhibitors. The review presents new data on the efficacy and safety of the new JAK inhibitor baricitinib in treating rheumatoid arthritis and other IMIRDs.

Pharmacoeconomic analysis of biological treatments for psoriatic arthritis

2006 ◽  
Vol 7 (3) ◽  
pp. 171-186 ◽  
Author(s):  
Mario Eandi ◽  
Carlo Salvarani
Keyword(s):  
Psoriatic Arthritis ◽  
Cost Effectiveness ◽  
Incremental Cost ◽  
Pharmacoeconomic Analysis ◽  
Cost Effective ◽  
Cost Utility ◽  
Phase Iii ◽  
Italian Market ◽  
Phase Iii Trials ◽  
Hands And Feet

Psoriatic arthritis is an inflammatory and possibly destructive form of arthritis; left untreated, psoriatic arthritis can be a progressively disabling disease. The arthritic manifestations often include debilitating disease of the hands and feet, as well as painful inflammation of the tendon insertions and arthritis of the spine. The most common treatments prescribed for the psoriatic arthritis are nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, corticosteroids and disease-modifying antirheumatic drugs (DMARDs). Due to a recently suggested role of the tumour necrosis factor (TNFα) in the pathogenesis of psoriatic arthritis, new therapies specifically blocking TNFα have been investigated. Aim of the present study is to compare cost/effectiveness (CEA) and cost/utility (CUA) ratios of anti-TNF medications currently available on the Italian market: etanercept, infliximab and adalimumab. The evaluation was conducted through the development of a single Markov model. Clinical data were obtained from three Phase III trials attesting the clinical efficacy of the biological therapies. Both cost/effectiveness and cost/utility analysis were implemented through the deterministic evaluation and the probabilistic evaluation, in order to assess the convenience for the Italian National Healthcare Service. Adalimumab appears to be cost effective for the treatment of psoriatic arthritis, especially considering the incremental cost/effectiveness ratio (ICER) and the incremental cost/utility ratio (ICUR); the results suggest that ICER and ICUR values of adalimumab over etanercept is definitely lower than the maximum acceptable willingness-to-pay value. Moreover, compared with infliximab, adalimumab is less costly and more effective.

scholarly journals JAK inhibitors and infections risk: focus on herpes zoster

2020 ◽  
Vol 12 ◽  
pp. 1759720X2093605
Author(s):  
Flavia Sunzini ◽  
Iain McInnes ◽  
Stefan Siebert
Keyword(s):  
Herpes Zoster ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Pathogenic Role ◽  
Immune Mediated ◽  
Post Marketing ◽  
Inflammatory Bowel

Currently, there is a growing interest in Janus kinase (JAK) intracellular signalling since targeted inhibitors against these pathways are proving effective in the treatment of a range of immune-mediated diseases, such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis (PsA), inflammatory bowel disease and atopic dermatitis. In particular, post marketing experience and the increasing development of new pharmacological inhibitors of broad and increasingly selective JAK pathways provide new insights into the JAK pathway role in viral infections as well as their pathogenic role in immune-mediated inflammatory diseases. Herein we provide an overview of the biological role of JAK signalling and its role in immunity against viruses, with particular regard to herpes zoster reactivation. Thereafter, we will discuss the evidence currently available on the principal JAK inhibitors and their association with viral infections.

Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis?

2017 ◽  
Vol 77 (2) ◽  
pp. 175-187 ◽  
Author(s):  
Kenneth F Baker ◽  
John D Isaacs
Keyword(s):  
Lupus Erythematosus ◽  
First Generation ◽  
Inflammatory Diseases ◽  
Cellular Adhesion ◽  
Janus Kinase ◽  
Type I ◽  
Jak Inhibitors ◽  
T Helper 17 ◽  
Immune Mediated ◽  
Sphingosine 1 Phosphate

The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide. We review novel biologic agents targeting the T-helper 17 axis, including therapies directed towards interleukin (IL)-17 (secukinumab, ixekizumab, bimekizumab), IL-17R (brodalumab), IL-12/23p40 (ustekinumab, briakinumab) and IL-23p19 (guselkumab, tildrakizumab, brazikumab, risankizumab, mirikizumab). We also present an overview of biologics active against type I and II interferons, including sifalumumab, rontalizumab, anifrolumab and fontolizumab. Emerging strategies to interfere with cellular adhesion processes involved in lymphocyte recruitment are discussed, including both integrin blockade (natalizumab, vedolizumab, etrolizumab) and sphingosine-1-phosphate receptor inhibition (fingolimod, ozanimod). We summarise the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib) and second-generation selective JAK inhibitors (decernotinib, filgotinib, upadacitinib). New biologics targeting B-cells (including ocrelizumab, veltuzumab, tabalumab and atacicept) and the development of novel strategies for regulatory T-cell modulation (including low-dose IL-2 therapy and Tregitopes) are also discussed. Finally, we explore recent biotechnological advances such as the development of bispecific antibodies (ABT-122, COVA322), and their application to the treatment of IMIDs.

Sign in / Sign up

Export Citation Format

Share Document