Evolution of treatment options for juvenile idiopathic arthritis

A recent study published in World J Clin Cases addressed the optimal non-steroidal anti-inflammatory drugs(NSAIDs)for juvenile idiopathic arthritis(JIA).Herein,we outline the progress in drug therapy of JIA.NSAIDs have traditionally been the primary treatment for all forms of JIA.NSAIDs are symptom-relief medications,and well tolerated by patients.Additionally,the availability of selective NSAIDs further lower the gastrointestinal adverse reactions compared with traditional NSAIDs.Glucocorticoid is another kind of symptom-relief medications with potent anti-inflammatory effect.However,the frequent adverse events limit the clinical use.Both NSAIDs and glucocorticoid fail to ease or pre-vent joint damage,and the breakthrough comes along with the disease-mo-difying antirheumatic drugs(DMARDs).DMARDs can prevent disease pro-gression and reduce joint destruction.Particularly,the emergence of biologic DMARDs(bDMARDs)has truly revolutionized the therapeutics of JIA,compared with conventional synthetic DMARDs.As a newly developed class of drugs,the places of most bDMARDs in the management of JIA remain to be well estab-lished.Nevertheless,the continuous evolution of bDMARDs raises hopes of improving long-term disease outcomes for JIA.

Hepatitis B virus reactivation in rheumatoid arthritis

Rheumatoid arthritis(RA)is an autoimmune disease characterized by proliferative synovitis,which can cause cartilage and bone damage as well as functional limitations.Disease-modifying anti-rheumatic drugs have significantly improved the prognosis of RA patients.However,people with RA,when combined with hepatitis B virus(HBV)infection,may experience reactivation of HBV during treatment with anti-rheumatic drugs.The outcome of HBV reactivation(HBVr)varies from liver inflammation to liver failure,while insufficient HBV screening in RA patients has been reported in various countries.Therefore,it is necessary to identify patients at high risk before starting immunosuppressive therapy.The immune response plays an important role in anti-HBV infection.However,most anti-rheumatic drugs exert an inhibitory effect on the body’s immune system,resulting in HBVr.Therefore,it is necessary to conduct a comprehensive evaluation based on host factors,viral factors,and drug factors.In this paper,we summarize the mechanism of HBVr,the risk of HBVr caused by anti-rheumatic drugs,and the appropriate diagnosis and treatment process for RA patients so that clinicians can have a more comprehensive understanding of HBVr in RA patients.

Hepatitis B virus infection reactivation in patients under immunosuppressive therapies:Pathogenesis,screening,prevention and treatment

With a 5.3%of the global population involved,hepatitis B virus(HBV)is a major public health challenge requiring an urgent response.After a possible acute phase,the natural history of HBV infection can progress in chronicity.Patients with overt or occult HBV infection can undergo HBV reactivation(HBVr)in course of immunosuppressive treatments that,apart from oncological and hematological diseases,are also used in rheumatologic,gastrointestinal,neurological and dermatological settings,as well as to treat severe acute respiratory syndrome coronavirus 2 infection.The risk of HBV reactivation is related to the immune status of the patient and the baseline HBV infection condition.The aim of the present paper is to investigate the risk of HBVr in those not oncological settings in order to suggest strategies for preventing and treating this occurrence.The main studies about HBVr for patients with occult hepatitis B infection and chronic HBV infection affected by non-oncologic diseases eligible for immunosuppressive treatment have been analyzed.The occurrence of this challenging event can be reduced screening the population eligible for immunosuppressant to assess the best strategies according to any virological status.Further prospective studies are needed to increase data on the risk of HBVr related to newer immunomodulant agents employed in non-oncological setting.

Treatment Adherence of Patients with Rheumatoid Arthritis during COVID-19 Pandemic

India is no exception to the economic setback due to coronavirus disease 2019 (COVID-19). Loss of jobs and income dramatically impacts the health care cost of chronic disease management. Rheumatoid arthritis is a chronic condition with a high-cost implication. With the outbreak of COVID-19, there is uncertainty about continuing immunosuppressive therapy for rheumatoid arthritis for several reasons. In this milieu, we undertook a prospective observational study to observe the use of Janus Kinase (JAK) inhibitors in a hospital-based rheumatology service in Eastern India during the pandemic period (21 March 2020 to 31 July 2020). Forty-two patients with rheumatoid arthritis were receiving treatment with JAK inhibitors. Twenty-four patients visited the Outpatient Department (OPD) during the COVID-19 pandemic. All of them were COVID-negative, but few of the patients had influenza-like symptoms. Patients faced up to a 25% reduction in their annual income during the COVID-19 pandemic. Of 24 patients, four patients had stopped treatment with JAK inhibitors owing to financial constraints or initial non-availability of medications during the lockdown. In this study, adherence to JAK inhibitors was substantially high even in the face of income curtailment during the COVID-19 pandemic.

What is the best biological treatment for rheumatoid arthritis? A systematic review of effectiveness

AIM:To evaluate the effectiveness of the biological disease-modifying antirheumatic drugs(b DMARD) in the treatment of rheumatoid arthritis through a systematic review of observational studies.METHODS:The studies were searched in the Pub Med,EMBASE,Cochrane Controlled Trials Register and LILACS databases(until August 2014),in the grey literature and conducted a manual search.The assessed criteria of effectiveness included the EULAR,the disease activity score(DAS),the Clinical Disease Activity Index,the Simplified Disease Activity Index,the American College of Rheumatology and the Health Assessment Questionnaire.The meta-analysis was performed with Review Manager 5.2 software using a random effects model.A total of 35 studies were included in this review.RESULTS:The participants anti-tumor necrosis factor inhibitors(TNF) nave,who used adalimumab(P = 0.0002) and etanercept(P = 0.0006) exhibited greater good EULAR response compared to the participants who used infliximab.No difference was detected between adalimumab and etanercept(P = 0.05).The participants who used etanercept exhibited greater remission according to DAS28 compared to the participants who used infliximab(P = 0.01).No differences were detected between adalimumab and infliximab(P = 0.12) or etanercept(P = 0.79).Better results were obtained with b DMARD associated with methotrexate than with b DMARD alone.The good EULAR response and DAS 28 was better for combination with methotrexate than b DMARD monotherapy(P = 0.03 e P < 0.00001).In cases of therapeutic failure,the participants who used rituximab exhibited greater DAS28 reduction compared to those who used anti-TNF agents(P = 0.0002).The participants who used etanercept achieved greater good EULAR response compared to those who did not use that drug(P = 0.007).Studies that assessed reduction of the CDAI score indicated the superiority of abatacept over rituximab(12.4 vs +1.7) and anti-TNF agents(7.6 vs 8.3).The present systematic review with meta-analysis found that relative to anti-TNF treatmentnave patients,adalimumab and etanercept were more effective when combined with methotrexate than when used alone.Furthermore,in case of therapeutic failure with anti-TNF agents;rituximab and abatacept(non anti-TNF) and etanercept(as second anti-TNF) were more effective.However,more studies of effectiveness were found for the rituximab.CONCLUSION:The best treatment for treatment-nave patients is adalimumab or etanercept combined with methotrexate.For anti-TNF therapeutic failure,the best choice is rituximab,abatacept or etanercept.

Remission is not maintained over 2 years with hematopoietic stem cell transplantation for rheumatoid arthritis:A systematic review with meta-analysis

BACKGROUND Hematopoietic stem cell(HSC)transplantation(HSCT)is being accepted as a standard of care in various inflammatory diseases.The treatment of rheumatoid arthritis(RA)has been closely evolving with the understanding of disease pathogenesis.With the rising resistance to the traditional disease-modifying antirheumatic drugs and targeted biological therapy,researchers are in pursuit of other methods for disease management.Since the ultimate goal of the ideal treatment of RA is to restore immune tolerance,HSCT attracts much attention considering its reparative,paracrine,and anti-inflammatory effects.However,a systematic review of studies on HSCT in RA is lacking.AIM To investigate the role of HSCT in the management of RA.METHODS A detailed search of PubMed,Scopus,EMBASE,Cochrane,and the Web of Science databases was made to identify the relevant articles till September 2020 following Cochrane and PRISMA guidelines.We extracted data including the number of patients,source of hematopoietic stem cells,their mobilization and conditioning regimens,results,and complications from the eligible studies.Results were dichotomized into success(ACR 50/70)and failure(ACR 20)based on the improvement from baseline characteristics.The methodological quality of the included studies was also assessed.Analysis was performed using OpenMeta[Analysis]software.RESULTS We included 17 studies(1 randomized controlled trial,11 prospective,and 5 retrospective studies)with 233 patients for analysis.HSCT provided a significantly beneficial overall improvement in the clinical grades of ACR criteria(Z=11.309,P<0.001).However,the remission was noted only till 24 mo and later on the significance of the result was lost(Z=1.737,P=0.082).A less than 1%treatmentrelated mortality was noted from the included studies.No major drug-related toxicities were noted in any of the included studies.All patients who underwent allogeneic HSCT received immunosuppression in the conditioning regimen to counteract the graft-vs-host reaction which made them vulnerable to infections.It is noted that the source of hematopoietic stem cells did not play a role in altering the functional outcome and both autologous(Z=9.972,P<0.001)and allogenic(Z=6.978,P<0.001)sources produced significant improvement in the outcome compared to the pre-operative state despite having a significant heterogeneity among the studies reporting them(I2=99.4,P<0.001).CONCLUSION Although the available literature is encouraging towards the use of HSCT in refractory cases with significant improvement from baseline till 2 years,the inclusion of HSCT into the standard of care of RA needs further exploration.

Role of JAK-STAT signaling pathway in pathogenesis and treatment of primary Sjögren’s syndrome

Primary Sjögren’s syndrome(pSS)is a systemic autoimmune disease with high prevalence and possible poor prognosis.Though the pathogenesis of pSS has not been fully elucidated,B cell hyperactivity is considered as one of the fundamental abnormalities in pSS patients.It has long been identified that Janus kinases-signal transducer and activator of transcription(JAK-STAT)signaling pathway contributes to rheumatoid arthritis and systemic lupus erythematosus.Recently,increasing numbers of studies have provided evidence that JAK-STAT pathway also has an important role in the pathogenesis of pSS via direct or indirect activation of B cells.Signal transducer and activator of transcription 1(STAT1),STAT3,and STAT5 activated by various cytokines and ribonucleic acid contribute to pSS development,respectively or synergically.These results reveal the potential application of Janus kinase inhibitors for treatment of pSS,which may fundamentally improve the quality of life and prognosis of patients with pSS.