scholarly journals Efficacy and Safety of Janus Kinase Inhibitors in Type I Interferon-Mediated Monogenic Autoinflammatory Disorders: A Scoping Review

2021 ◽  
Author(s):  
Pedro Jesús Gómez-Arias ◽  
Francisco Gómez-García ◽  
Jorge Hernández-Parada ◽  
Ana María Montilla-López ◽  
Juan Ruano ◽  
...  
Keyword(s):  
Scoping Review ◽  
Kinase Inhibitors ◽  
Type I Interferon ◽  
Janus Kinase ◽  
Type I ◽  
Efficacy And Safety ◽  
Autoinflammatory Disorders ◽  
Janus Kinase Inhibitors

scholarly journals JAK-Inhibitor and Type I Interferon Ability to Produce Favorable Clinical Outcomes in COVID-19 Patients: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Lucas Walz ◽  
Avi J. Cohen ◽  
Andre P. Rebaza ◽  
James Vanchieri ◽  
Martin D. Slade ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Type I Interferon ◽  
Meta Analysis ◽  
Janus Kinase ◽  
Type I Interferons ◽  
Type I ◽  
Janus Kinase Inhibitor ◽  
Janus Kinase Inhibitors

Abstract Background The spread of a highly pathogenic, novel coronavirus (SARS-CoV-2) has emerged as a once-in-a-century pandemic, having already infected over 17 million. Novel therapies are urgently needed. Janus kinase-inhibitors and Type I interferons have emerged as potential antiviral candidates for COVID-19 patients for their proven efficacy against diseases with excessive cytokine release and due to direct antiviral ability against viruses including coronaviruses, respectively. We conducted a systemic review and meta-analysis to evaluate the effect of Janus kinase-inhibitors and Type I interferons and their ability to produce positive patient outcomes in COVID-19 patients. Methods A search of MEDLINE and MedRxiv was conducted by three investigators from inception until July 30 th 2020, including any study type that compared treatment outcomes of humans treated with JAK-inhibitor or Type I interferon against controls. Inclusion necessitated data with clearly indicated risk estimates or those that permitted their back-calculation. Outcomes were synthesized using RevMan. Results Of 733 searched studies, we included four randomized and eleven non-randomized trials. Five of the studies were unpublished. Those who received Janus kinase-inhibitor had significantly reduced odds of mortality (OR, 0.12; 95% CI, 0.03 – 0.39, p<0.001) and ICU admission (OR, 0.05; 95% CI, 0.01 – 0.26, p<0.001), and had significantly increased odds of hospital discharge (OR, 22.76; 95% CI, 10.68 – 48.54, p<0.00001), when compared to standard treatment group. Type I interferon recipients had significantly reduced odds of mortality (OR, 0.19; 95% CI, 0.04 – 0.85, p<0.05), and increased odds of discharge bordering significance (OR, 1.89; 95% CI, 1.00 – 3.59, p=0.05). Conclusions Janus kinase-inhibitor treatment is significantly associated with positive clinical outcomes in terms of mortality, ICU admission, and discharge. Type I interferon treatment is associated with positive clinical outcomes in regard to mortality and discharge. While these data show promise, additional well-conducted RCTs are needed to further elucidate the relationship between clinical outcomes and Janus kinase-inhibitors and Type I interferons in COVID-19 patients.

Drug efficacy and safety of biologics and Janus kinase inhibitors in elderly patients with rheumatoid arthritis

2021 ◽  
Author(s):  
Kosuke Ebina
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Elderly Patients ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Treatment Recommendation ◽  
Efficacy And Safety ◽  
Old Patients ◽  
Janus Kinase Inhibitors ◽  
Increased Risk

ABSTRACT Elderly patients with rheumatoid arthritis (RA) are frequently associated with higher disease activity and impaired physical function, although they show intolerance for conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate, because of their comorbidities. However, the present treatment recommendation based on randomized controlled trials is not distinguished by age or comorbidities. Therefore, this review aimed to investigate the efficacy and safety of biological DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi) in elderly patients. Present bDMARDs, including tumor necrosis factor inhibitors (TNFi), cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (abatacept), interleukin (IL)-6 receptor antibody (tocilizumab and salirumab), and anti-CD20 antibody (rituximab), may be similarly or slightly less effective or safe in elderly patients compared with younger patients. Oral glucocorticoid use, prolonged disease duration, and very old patients appear to be associated with an increased risk of adverse events, such as serious infection. Some recent cohort studies demonstrated that non-TNFi showed better retention than TNFi in elderly patients. Both TNFi and non-TNFi agents may not strongly influence the risk of adverse events such as cardiovascular events and malignancy in elderly patients. Regarding JAKi, the efficacy appears to be similar, although the safety (particularly for serious infections, including herpes zoster) may be attenuated by aging.

JAK Inhibition as a Therapeutic Strategy for Inflammatory Bowel Disease

2020 ◽  
Vol 21 (4) ◽  
pp. 247-255 ◽  
Author(s):  
Fabio Salvatore Macaluso ◽  
Iago Rodríguez-Lago
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Mechanism Of Action ◽  
Bowel Disease ◽  
Therapeutic Strategy ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Efficacy And Safety ◽  
Janus Kinase Inhibitors ◽  
Inflammatory Bowel

Background: Inflammatory bowel disease, including both Crohn’s disease and ulcerative colitis, are two chronic and progressive disorders affecting the gastrointestinal tract. Research on the molecular mechanisms of both diseases has led to the introduction of targeted therapies which are able to selectively block the key inflammatory mediators. Methods: Here, we discuss the current evidence about the mechanism of action with an up to date review of the efficacy and safety of Janus kinase inhibitors in inflammatory bowel disease. Results: Multiple small molecule drugs have been evaluated for their use in both ulcerative colitis and Crohn’s disease. Janus kinase inhibitors represent the most important family of these drugs, as their particular mechanism of action enables a simultaneous and effective blockade of multiple cytokines involved in the pathogenesis of the disease. Conclusion: Janus kinase inhibitors represent a promising therapeutic strategy, especially in ulcerative colitis. More data are still necessary regarding its efficacy and safety in clinical practice.

scholarly journals Pulmonary arterial hypertension in interferonophaties: a case report and a review of the literature

2019 ◽  
Vol 9 (3) ◽  
pp. 204589401986983 ◽  
Author(s):  
A. Trombetta ◽  
S. Ghirardo ◽  
S. Pastore ◽  
A. Tesser ◽  
E. Piscianz ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Lupus Erythematosus ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Type I ◽  
Systemic Lupus ◽  
Janus Kinase Inhibitors ◽  
Pulmonary Arterial

Background Pulmonary arterial hypertension consists in an increase of mean pulmonary arterial pressure (PAPm ≥ 25 mmHg), and may lead to right ventricular failure. Pulmonary arterial hypertension can arise in several disorders, encompassing inflammatory conditions and connective tissue diseases. The occurrence of pulmonary arterial hypertension has recently been reported in monogenic interferonopathies and in systemic lupus erythematosus, highlighting the pathogenic role of type I interferons and paving the way to therapies aimed at inhibiting interferon signaling. Case We describe a 17-year-old boy with DNase II deficiency, presenting a clinical picture with significant overlap with systemic lupus erythematosus. During treatment with the Janus kinase inhibitor ruxolitinib, he developed pulmonary arterial hypertension, raising the question whether it could represent a sign of insufficient disease control or a drug-related adverse event. The disease even worsened after drug withdrawal, but rapidly improved after starting the drug again at higher dosage. Summary and conclusion Pulmonary arterial hypertension can complicate type I interferonopathies. We propose that ruxolitinib was beneficial in this case, but the wider role of Janus kinase inhibitors for the treatment of pulmonary arterial hypertension is not clear. For this reason, a strict cardiologic evaluation must be part of the standard care of subjects with interferonopathies, especially when Janus kinase inhibitors are prescribed.

scholarly journals APPLICATION OF JANUS-KINASE INHIBITORS IN THE TREATMENT OF ALOPECIA AREATA (LITERATURE REVIEW)

2019 ◽  
Vol 22 (1-2) ◽  
pp. 61-64
Author(s):  
Anfisa A. Lepekhova ◽  
L. M Chernyavskaya
Keyword(s):  
Literature Review ◽  
Mechanism Of Action ◽  
Alopecia Areata ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Targeted Drugs ◽  
Efficacy And Safety ◽  
Janus Kinase Inhibitors ◽  
Immune Mediated ◽  
Adults And Children

Based on the analysis of data from modern foreign sources current information about using of Janus-kinase inhibitors, in particular, tofacitinid and ruxolitinid, for the treatment of alopecia areata in adults and children, in the presence of a lesion of the scalp and other areas (eyebrows, eyelashes) is shown. The information about the mechanism of action of Janus-kinase inhibitors, the efficacy and safety of their use, possible methods of use, prospects for further research in the treatment of alopecia areata using targeted drugs is presented. The pathogenetic rationale for the possibility of using this group of drugs for treating immune-mediated diseases, for instance, alopecia areata is described.

scholarly journals Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a consensus statement

2020 ◽  
Vol 80 (1) ◽  
pp. 71-87 ◽  
Author(s):  
Peter Nash ◽  
Andreas Kerschbaumer ◽  
Thomas Dörner ◽  
Maxime Dougados ◽  
Roy M Fleischmann ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Consensus Statement ◽  
Task Force ◽  
Inflammatory Diseases ◽  
Steering Committee ◽  
Janus Kinase ◽  
Expert Committee ◽  
Efficacy And Safety ◽  
Janus Kinase Inhibitors ◽  
Immune Mediated

ObjectivesJanus kinase inhibitors (JAKi) have been approved for use in various immune-mediated inflammatory diseases. With five agents licensed, it was timely to summarise the current understanding of JAKi use based on a systematic literature review (SLR) on efficacy and safety.MethodsExisting data were evaluated by a steering committee and subsequently reviewed by a 29 person expert committee leading to the formulation of a consensus statement that may assist the clinicians, patients and other stakeholders once the decision is made to commence a JAKi. The committee included patients, rheumatologists, a gastroenterologist, a haematologist, a dermatologist, an infectious disease specialist and a health professional. The SLR informed the Task Force on controlled and open clinical trials, registry data, phase 4 trials and meta-analyses. In addition, approval of new compounds by, and warnings from regulators that were issued after the end of the SLR search date were taken into consideration.ResultsThe Task Force agreed on and developed four general principles and a total of 26 points for consideration which were grouped into six areas addressing indications, treatment dose and comedication, contraindications, pretreatment screening and risks, laboratory and clinical follow-up examinations, and adverse events. Levels of evidence and strengths of recommendations were determined based on the SLR and levels of agreement were voted on for every point, reaching a range between 8.8 and 9.9 on a 10-point scale.ConclusionThe consensus provides an assessment of evidence for efficacy and safety of an important therapeutic class with guidance on issues of practical management.

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