scholarly journals Antirheumatic Drugs against COVID-19 from the Perspective of Rheumatologists

2021 ◽  
Vol 14 (12) ◽  
pp. 1256
Author(s):  
Mai Kawazoe ◽  
Mari Kihara ◽  
Toshihiro Nanki
Keyword(s):  
Disease Progression ◽  
Kinase Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Immunosuppressive Treatment ◽  
Calcineurin Inhibitors ◽  
Immunosuppressive Drugs ◽  
Janus Kinase ◽  
Viral Inhibition ◽  
Patient Death ◽  
Antirheumatic Drugs

Coronavirus disease 2019 (COVID-19) remains a global threat to humanity. Its pathogenesis and different phases of disease progression are being elucidated under the pandemic. Active viral replication activates various immune cells and produces large amounts of inflammatory cytokines, which leads to the cytokine storm, a major cause of patient death. Therefore, viral inhibition is expected to be the most effective early in the course of the disease, while immunosuppressive treatment may be useful in the later stages to prevent disease progression. Based on the pathophysiology of rheumatic diseases, various immunomodulatory and immunosuppressive drugs are used for the diseases. Due to their mechanism of action, the antirheumatic drugs, including hydroxychloroquine, chloroquine, colchicine, calcineurin inhibitors (e.g., cyclosporine A and tacrolimus), glucocorticoids, cytokines inhibitors, such as anti-tumor necrosis factor-α (e.g., infliximab), anti-interleukin (IL)-6 (e.g., tocilizumab, sarilumab, and siltuximab), anti-IL-1 (e.g., anakinra and canakinumab) and Janus kinase inhibitors (e.g., baricitinib and tofacitinib), cytotoxic T lymphocyte-associated antigen 4 blockade agents (e.g., abatacept), and phosphodiesterase 4 inhibitors (e.g., apremilast), have been tried as a treatment for COVID-19. In this review, we discuss the mechanisms of action and clinical impact of these agents in the management of COVID-19.

scholarly journals Influence of TGFB1 and CTLA4 polymorphisms on calcineurin inhibitors dose and risk of acute rejection in renal transplantation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Bogacz ◽  
Marlena Wolek ◽  
Jerzy Sieńko ◽  
Bogusław Czerny ◽  
Bogusław Machaliński ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Immunosuppressive Treatment ◽  
Calcineurin Inhibitors ◽  
Immunosuppressive Drugs ◽  
Dose Ratio ◽  
Blood Concentrations ◽  
Organ Rejection ◽  
Transplant Patients ◽  
The Impact ◽  
Tgf Β1

AbstractOrgan transplant is often the treatment of choice as it extends and improves patient life. Immunosuppressive treatment, which prevents acute rejection of the organ, is used in transplant patients to prevent the loss of transplant. The aim of the study was to determine the impact of the CTLA4 (+49A>G, rs231775) and the TGF-β1 (−800G>A, rs1800468) polymorphisms on the therapeutic effect of immunosuppressive drugs (cyclosporine—CsA, tacrolimus—TAC) and the risk of acute rejection in renal transplant patients. The analysis of the CTLA4 +49A>G and the TGF-β1 −800G>A polymorphisms was carried out in 392 patients after kidney transplant using real-time PCR. The CTLA4 +49A>G polymorphism did not affect CsA or TAC dose, ratio of drug concentration to dose (C/D), and blood concentrations. As for the TGF-β1 -800G>A polymorphism, patients with the GA genotype required lower TAC doses compared to the GG genotype (TAC 12 h: 3.63 mg vs 5.3 mg, TAC 24 h: 2.38 mg vs 3.29 mg). Comparing the C/D ratio in both groups (TAC 12 h and TAC 24 h), higher C/D ratio was observed in patients with the GA genotype. These results indicate that patients with the A allele require slightly lower doses of TAC. The results suggest that the TGF-β1 −800 G>A polymorphism may influence the TAC dose, while the +49A>G polymorphism of the CTLA4 gene does not correlate with the dose of CsA or TAC. The analysis of the biochemical parameters of the renal profile showed no impact of the CTLA4 and the TGF-β1 polymorphisms on the risk of organ rejection.

scholarly journals Transient Efficacy of Tofacitinib in Alopecia Areata Universalis

2016 ◽  
Vol 8 (1) ◽  
pp. 102-106 ◽  
Author(s):  
Florian Anzengruber ◽  
Julia-Tatjana Maul ◽  
Jivko Kamarachev ◽  
Ralph M. Trüeb ◽  
Lars E. French ◽  
...  
Keyword(s):  
Treatment Option ◽  
Alopecia Areata ◽  
Kinase Inhibitors ◽  
Autoimmune Disorder ◽  
Immunosuppressive Drugs ◽  
Hair Follicles ◽  
Janus Kinase ◽  
Individual Treatment ◽  
Immune Therapies ◽  
New Treatment

Alopecia areata is a common autoimmune disorder that targets hair follicles. Swarms of lymphocytes surround the basis of the follicles, inducing loss of pigmented terminal hair and subsequently inhibit further hair growth. Depending on the extent of involvement, alopecia areata can be associated with a dramatic reduction of quality of life. Currently, no targeted treatment option is available, and topical immune therapies or immunosuppressive drugs are typically used with mixed success. Recently, several cases of alopecia areata responding to Janus kinase inhibitors were published. Here, we report on a businessman with alopecia areata universalis who was treated with tofacitinib. We observed initial signs of hair regrowth in the same timeframe as previously reported, but efficacy quickly waned again, leading to renewed effluvium. Thus, even though tofacitinib and ruxolitinib are a promising new treatment option, we have yet to learn more about their potential role in each particular patient's individual treatment strategy.

JAK inhibitors are effective in a subset of patients with juvenile dermatomyositis: a monocentric retrospective study

Rheumatology ◽  
2021 ◽  
Author(s):  
Tom Le Voyer ◽  
Cyril Gitiaux ◽  
François-Jérôme Authier ◽  
Christine Bodemer ◽  
Isabelle Melki ◽  
...  
Keyword(s):  
Herpes Zoster ◽  
Retrospective Study ◽  
Skin Disease ◽  
Kinase Inhibitors ◽  
Immunosuppressive Drugs ◽  
Janus Kinase ◽  
High Rate ◽  
Inactive Disease ◽  
Muscle Involvement ◽  
New Onset

Abstract Objective To evaluate the efficacy and safety of Janus kinase inhibitors (JAKis) in JDM. Methods We conducted a single-centre retrospective study of patients with JDM treated by JAKi with a follow-up of at least 6 months. Proportion of clinically inactive disease (CID) within 6 months of JAKi initiation was evaluated using PRINTO criteria and skin Disease Activity Score. Serum IFN-α concentration was measured by Simoa assay. Results Nine refractory and one new-onset patients with JDM treated with ruxolitinib (n = 7) or baricitinib (n = 3) were included. The main indications for treatment were refractory muscle involvement (n = 8) and ulcerative skin disease (n = 2). CID was achieved in 5/10 patients (two/two anti-MDA5, three/four anti-NXP2, zero/three anti-TIF1γ-positive patients) within 6 months of JAKi introduction. All responders could withdraw plasmatic exchange, immunoadsorption and other immunosuppressive drugs. The mean daily steroid dose decreased from 1.1 mg/kg (range 0.35–2 mg/kg/d) to 0.1 (range, 0–0.3, P = 0.008) in patients achieving CID, and was stopped in two. Serum IFN-α concentrations were elevated in all patients at the time of treatment initiation and normalized in both responder and non-responder. A muscle biopsy repeated in one patient 26 months after the initiation of JAKi, showed a complete restoration of muscle endomysial microvascular bed. Herpes zoster and skin abscesses developed in three and two patients, respectively. Conclusion JAKis resulted in a CID in a subset of new-onset or refractory patients with JDM and may dramatically reverse severe muscle vasculopathy. Overall tolerance was good except for a high rate of herpes zoster infection.

scholarly journals Reactivation of hepatitis B virus infection in rheumatic diseases: risk and management considerations

2020 ◽  
Vol 12 ◽  
pp. 1759720X2091264 ◽  
Author(s):  
Christos Koutsianas ◽  
Konstantinos Thomas ◽  
Dimitrios Vassilopoulos
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Rheumatic Diseases ◽  
Antiviral Treatment ◽  
Immunosuppressive Treatment ◽  
Immunosuppressive Drugs ◽  
Janus Kinase ◽  
Virus Reactivation ◽  
Specific Risk ◽  
B Virus

In patients with rheumatic diseases undergoing immunosuppressive treatment, hepatitis B virus reactivation (HBVr) has been long recognized as a major treatment-related adverse event with substantial morbidity and mortality. Because HBVr is easily preventable with appropriate screening and monitoring strategies, and, when indicated, prophylactic antiviral treatment, awareness of this complication is of the utmost importance, especially in the era of biologic treatments. As a condition, it continues to be topical, in view of the emergence of novel classes of immunosuppressive drugs (i.e. Janus kinase inhibitors) acquiring licenses for a variety of rheumatic diseases. The class-specific risk of these agents for HBVr has not yet been determined. Moreover, ambiguity still exists for the management of patients planned to be treated with traditional agents, such as cyclophosphamide and glucocorticoids, particularly in the setting of resolved HBV infection. Clinicians in the field of rheumatic diseases should be tailoring their practice according to the host’s profile and treatment-specific risk for HBVr. In this review, the authors attempt to critically review the existing literature and provide practical advice on these issues.

scholarly journals Non-surgical treatment of vitiligo

2020 ◽  
Vol 63 (12) ◽  
pp. 741-747
Author(s):  
Chong Won Choi
Keyword(s):  
Surgical Treatment ◽  
Kinase Inhibitors ◽  
Calcineurin Inhibitors ◽  
Autoimmune Disorder ◽  
Skin Lesions ◽  
Ultraviolet B ◽  
Janus Kinase ◽  
Treatment Modalities ◽  
Pigmented Lesions ◽  
Non Surgical Treatment

Vitiligo is an acquired depigmenting skin disorder that affects 0.5% to 2% of the population. Skin lesions from vitiligo, white macules and patches on the skin, can pose a substantial psychological burdencan, causing a significant decrease in one’s quality of life. Recent basic and clinical studies have found that vitiligo is an autoimmune disorder, mediated by CD8+ T-cell and interferon-γ-mediated cytokine/chemokines. Although no treatment modality presents a complete cure for vitiligo, current treatment modalities have a modest effect on vitiligo by reversing the disease’s progression, inducing its stabilization, and promoting melanocyte regeneration. Current non-surgical treatment modalities include topical corticosteroids, topical calcineurin inhibitors, systemic corticosteroids, and phototherapy such as narrowband ultraviolet B phototherapy and excimer laser. In addition, clinicians have used and combined non-surgical treatment modalities based on the activity and extent of vitiligo. Moreover, considering the high risk of vitiligo relapse, maintenance therapy for re-pigmented lesions has also been introduced. Lastly, based on the results of recent translational research, new and emerging treatment modalities have been introduced, such as Janus kinase inhibitors. This review presents an overview of the current non-surgical treatment modalities for vitiligo and discusses emerging treatments.

scholarly journals POS0088 EFFICACY OF JANUS KINASE INHIBITORS FOR DIFFICULT-TO-TREAT RA IN CLINICAL PRACTICE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 252-253
Author(s):  
M. Kamiya ◽  
D. Togawa ◽  
S. Mori ◽  
K. Yamazaki
Keyword(s):  
Rheumatoid Arthritis ◽  
Kinase Inhibitors ◽  
Retention Rate ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Janus Kinase Inhibitors ◽  
Necrosis Factor ◽  
Drug Retention Rate

Background:In 20-30% of rheumatoid arthritis (RA) patients, the first biologic disease-modifying antirheumatic drugs (bDMARDs) (generally tumour necrosis factor inhibitors (TNFis)) is ineffective, and among the patients who do respond to therapy, 20% is faced with secondary ineffectiveness within the first 2 years of treatment [1]. In practice, when refractory RA is present, of which the definition implies previous use of at least two bDMARDs (generally TNFis), the next treatment choice often made is a bDMARD of another class (non-TNFis) [2]. On the other hand, patients who are inadequately responding to bDMARDs need new treatment options because subsequent bDMARD treatment reduces their response [3]. Janus Kinase inhibitors (JAKis) are the first targeted synthetic DMARDs (tsDMARD) licensed for the treatment of RA with comparable efficacy to bDMARDs. Unlike the single cytokine targeting approach of bDMARDs, JAKis are specifically designed to inhibit intracellular signalling molecules common to the receptors of multiple inflammatory cytokines implicated in RA pathogenesis.Objectives:Difficult-to-treat (D2T) RA is defined as refractory to two or more b/ts DMARDs with different mechanisms of action, with active and progressive disease, as published by Eular(4). We evaluated real world efficacy of approved JAKis and factors that may help to continue them in patients with D2T RA.Methods:Patients who had inadequate response to two or more bDMARDs (including both TNFis and non-TNFis) at our hospital by December 2019 were defined as D2T RA, and patients who switched to JAKis were retrospectively investigated. The drug retention rate was determined by Kaplan-Meier method, and the difference was tested by Logrank test. Multiple regression analysis was used as the statistical method to predict continuation of JAKis for more than 1 year, with patient background (age, gender, during the disease, number of bDMARDs used, with or without methotrexate and/or glucocorticoids, disease activity score assessing 28 joints using erythrocyte sedimentation rate’ presence of rheumatoid factor/anti-CCP antibody, matrix metalloproteinase 3 value, Health Assessment Questionnaire disability index) at the time of initiation as an explanatory variable.Results:A total of 915 bDMARDs had been administered to 394 RA patients. The retention rate of bDMARDs and the number of bDMARDs used were 89.3% and 1.48 bDMARDs at 1 year, 67.7% and 2.27 bDMARDs at 5 years, and 52.0% and 3.15 bDMARDs at 10 years, respectively. The retention rate of JAKis at 1 year was 60.2% in 65 patients with tofacitinib (TOF) and 67.2% in 70 patients with baricitinib (BAR) (P=0.38). Among them, the drug retention rate in D2T RA patients was 50.8% in 38 TOF patients and 66.3% in 35 BAR patients with no significant difference (P=0.30). There were no patient background factors that significantly predicted continuation at 1 year for any JAKis.Conclusion:Despite the limited number of patients and the retrospective nature of the study, TOF and BAR were shown to be effective options for D2T RA, regardless of patient background such as disease activity or number of bDMARDs used. Other JAKis and switches between JAKis need to be investigated in the future.References:[1]Schaeverbeke T, Truchetet ME, Kostine M et al. Immunogenicity of biologic agents in rheumatoid arthritis patients: lessons for clinical practice. Rheumatology 2016;55:210_20.[2]Smolen JS, Landewe R, Bijlsma J et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960_77.[3]Rendas-Baum R, Wallenstein GV, Koncz T et al. Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors. Arthritis Res Ther 2011;13:R25.[4]Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80:31–35. doi:10.1136/annrheumdis-2020-217344.Disclosure of Interests:None declared

scholarly journals AB0712 THE INCIDENCE OF SARS-СOV-2 INFECTION IN PATIENTS WITH RHEUMATIC DISEASES ON THERAPY BIOLOGICAL DISEASE MODIFYING ANTIRHEUMATIC DRUGS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1387.3-1388
Author(s):  
A. Dadalova ◽  
E. Vasilenko ◽  
R. Samigullina ◽  
V. Mazurov
Keyword(s):  
Rheumatic Diseases ◽  
Interleukin 6 ◽  
Kinase Inhibitors ◽  
Biological Therapy ◽  
Janus Kinase ◽  
Interleukin 17 ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Tnf Α ◽  
Disease Modifying

Background:At the moment, a highly relevant issue is the course of SARS-CoV-2 infection in patients with rheumatic pathology, especially, those receiving therapy with biological disease modifying antirheumatic drugs.Objectives:of the current study to assess the prevalence and course of SARS-CoV-2 infection in patients receiving various biological disease modifying antirheumatic drugs.Methods:to assess the severity of the course of SARS-CoV-2, discharged epicrisis from hospitals or the conclusion of computed tomography were used. The average age of the patients ranged from 41.4 + 11.6 years. In the evaluated sample, 47 patients (49.47%) were males. Among the infected of SARS-CoV-2 were patients with rheumatoid arthritis - 45 (47.4%), spondyloarthritis - 39 (41.1%), systemic connective tissue diseases - 11 (11.5%).Results:Since March 2020, among the 1319 patients with rheumatic diseases observed at the St. Petersburg Center of therapy biological disease modifying antirheumatic drugs, 95 patients (7,2%) had SARS-CoV-2 infection. In 57,9% (55 patients) there was a mild course of infection, in 35,8% of cases (34 patients) - a moderate course, in 6,3% (6 patients) - a severe course. Inpatient treatment was received by 29,5% (28 patients). A favorable outcome was noted in 95.8%, and a lethal outcome in 4,2%. The use of interleukin-6 inhibitors was required in 2,1% of patients (2) due to the development of a cytokine storm. The structure of the received biological therapy in the severity of the course is shown in Table 1.Table 1.The structure of the received biological therapy in the severity of the course SARS-CoV-2 infectionMild courseCT-1 (<25%)CT-2 (25-50%)CT-3 (50-75%)CT-4 (>75%)TNF-α inhibitors, n (%)30 (31,6)11 (11,6)7 (7,3)3 (3,2)0 (0,0)anti B-cell therapy (rituximab), n (%)2 (2,1)1 (1,1)2 (2,1)1 (1,1)2 (2,1)Abatacept, n (%)3 (3.2)0 (0,0)2 (2,1)0 (0,0)0 (0,0)Janus kinase inhibitors, n (%)5 (5,3)1 (1,1)1 (1,1)0 (0,0)0 (0,0)Interleukin-6 inhibitors, n (%)6 (6,3)0 (0,0)0 (0,0)0 (0,0)0 (0,0)Interleukin-17 inhibitors, n (%)8 (8,4) 2 (2,1) 2 (2,1)0 (0,0)0 (0,0)Other, n (%)1 (1,1)4 (4,2)1 (1,1)0 (0,0)0 (0,0)Among 95 infected patients, who were observed in the center, 51 received therapy with TNF-α inhibitors (8.5% of the total number of patients receiving therapy), 8 - rituximab therapy (2.7%), 5 - abatacept (6.3%), 7 - Janus kinase inhibitors (0.9%), 6 – interleukin-6 inhibitors (9.2), 12 - interleukin -17 inhibitors (14.1%), 6 patients treated with other drugs (10%).Conclusion:Taking into account the SARS-CoV-2 pandemic, further study of the course of infection in patients with rheumatic diseases, including those receiving biological therapy, is required. More information is also needed on the safety and efficacy of vaccination in this patient population.Disclosure of Interests:None declared

Review of Atopic Dermatitis and Topical Therapies

2016 ◽  
Vol 21 (3) ◽  
pp. 227-236 ◽  
Author(s):  
Julia N. Mayba ◽  
Melinda J. Gooderham
Keyword(s):  
Atopic Dermatitis ◽  
Kinase Inhibitors ◽  
Calcineurin Inhibitors ◽  
Janus Kinase ◽  
Treatment Modalities ◽  
Comprehensive Overview ◽  
Topical Corticosteroids ◽  
Topical Calcineurin Inhibitors ◽  
Common Skin ◽  
New Treatments

Atopic dermatitis is one of the most common skin disorders in the developed world, affecting up to 20% of children and 1% to 3% of adults. This review concisely explains the pathophysiology and epidemiology of atopic dermatitis, as well as potential challenges facing its successful treatment. Furthermore, mainstay topical treatment modalities are evaluated, such as emollients, topical corticosteroids, and topical calcineurin inhibitors. The use of topical corticosteroids and topical calcineurin inhibitors in combination is discussed, as studies have indicated encouraging results. The proactive use of topical corticosteroids and topical calcineurin inhibitors is also investigated, in order to bring attention to a new possibility in long-term management of atopic dermatitis. Last, new and upcoming topical medications are described, including Janus kinase inhibitors, phosphodiesterase-4 inhibitors, and benvitimod. Although topical corticosteroids and topical calcineurin inhibitors can be very effective in the treatment of atopic dermatitis, it is important that practitioners are aware of mechanistically unique and new treatments for patients for whom more traditional topical therapies have failed. Overall, this review article hopes to serve as a comprehensive overview of currently available topical treatments for atopic dermatitis, while shedding light on new treatments coming in the future.

scholarly journals Janus Kinase Inhibitors for the Treatment of Rheumatoid Arthritis

2017 ◽  
Vol 52 (10) ◽  
pp. 667-668 ◽  
Author(s):  
Senir Turan ◽  
Scot Walker
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Reactions ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Oral Drugs ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Janus Kinase Inhibitors ◽  
Skin Conditions

Rheumatoid arthritis (RA) is a disease where the immune system attacks the linings of the joints, resulting in joint pain, stiffness, swelling, and destruction. Although many products are available for the treatment of RA, limitations such as adverse reactions and tolerance greatly affect adherence. Many of the current biologic disease-modifying antirheumatic drugs on the market are injectables, leaving a void to be filled for a product that can be taken orally. The most advanced of these approaches, the Janus kinase (JAK) inhibitors, are oral drugs that have not only made a breakthrough in RA, but also other skin conditions.

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