Hepatitis B virus reactivation associated with antirheumatic therapy: risk and prophylaxis recommendations

Accompanying the increased use of biological and non-biological antirheumatic drugs,a greater number of cases of hepatitis B virus(HBV) reactivation have been reported in inactive hepatitis B surface antigen(HBs Ag) carriers and also in HBs Ag-negative patients who have resolved HBV infection. The prevalence of resolved infection varies in rheumatic disease patients,ranging from 7.3% to 66%. Through an electronic search of the Pub Med database,we found that among 712 patients with resolved infection in 17 observational cohort studies,12 experienced HBV reactivation(1.7%) during biological antirheumatic therapy. Reactivation rates were 2.4% for etanercept therapy,0.6% for adalimumab,0% for infliximab,8.6% for tocilizumab,and 3.3% for rituximab. Regarding non-biological antirheumatic drugs,HBV reactivation was observed in 10 out of 327 patients with resolved infection from five cohort studies(3.2%). Most of these patients received steroids concomitantly. Outcomes were favorable in rheumatic disease patients. A number of recommendations have been established,but most of the supporting evidence was derived from the oncology and transplantation fields. Compared with patients in these fields,rheumatic disease patients continue treatment with multiple immunosuppressants for longer periods. Optimal frequency and duration of HBV-DNA monitoring and reliable markers for discontinuation of nucleoside analogues should be clarified for rheumatic disease patients with resolved HBV infection.

Observation on the Therapeutic Effect of Heatclearing and Dampness-eliminating Dredging Collaterals Combined with Papaya Antirheumatic Pills on Treatment of Damp-heat Obstructive Ankylosing Spondylitis

Objective:Therapeutic effect of heatclearing and dampness-eliminating dredging collaterals combined with papaya antirheumatic pills on treatment of damp-heat obstructive ankylosing spondylitis.Methods:A total of 200 patients with ankylosing spondylitis who were treated in our hospital from January 2018 to October 2019 were selected as the research objects and randomly divided into 2 groups,each with 100 patients.The control group was treated with leflunomide+papaya antirheumatic pills,and the observation group was treated with self-drafted recipe of heat-clearing and dampness-eliminating,the curative effect,visual analogue score(VAS),barthel AS function index(BASFI)score,biochemical indicators and adverse reactions between the two groups were compared.Results:After 12 weeks of treatment,the efficacy of the observation group was higher than that of the control group.The pain score,BASFI score,and biochemical index were lower than those of the control group,and the differences were statistically significant(P<0.05);There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Heat-clearing and dampnesseliminating dredging collaterals combined with papaya antirheumatic pills is effective in the treatment of damp-heat obstructive ankylosing spondylitis,which is beneficial to reduce the degree of pain and inflammation of the affected area,helps patients remain active,and improves activities of daily living.

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.

Perioperative management of the patient with rheumatoid arthritis

A multidisciplinary approach is required to care for patients with rheumatoid arthritis(RA)in the perioperative period.In preparation for surgery,patients must have a cardiovascular risk assessment performed due to the high risk of heart disease in patients with RA.Treatment of RA is with immunomodulatory medications,which present unique challenges for the perioperative period.Currently,there is no consensus on how to manage disease modifying antirheumatic drug(DMARD)therapy in the perioperative setting.Much of the data to guide therapy is based on retrospective cohort data.Choices regarding DMARDs require an individualized approach with collaboration between surgeons and rheumatologists.Consensus regarding biologic therapy is to hold the therapy in the perioperative period with the length of time dictated by the half-life of the medication.Special attention is required at the time of surgery for potential need for stress dose steroids.Further,there must be close communication with anesthesiologists in terms of airway management particularly in light of the risk for cervical spine disease.There are no consensus guidelines regarding the requirement for cervical spine radiographs prior to surgery.However,history and exam alone cannot be relied upon toidentify cervical spine disease.Patients with RA who undergo joint replacement arthroplasty are at higher risk for infection and dislocation compared to patients with osteoarthritis,necessitating particular vigilance in postoperative follow up.This review summarizes available evidence regarding perioperative management of patients with RA.

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.

Production of Gel with Menthol, Benzocaine and Procaine HCl for Topical Application in Rheumatoid Arthritis Patients

Antirheurnatic and analgesics drugs are the most commonly prescribed medications for treatment of acute and chronic pain. Frequent application of these agents often causes adverse effects. So, in order to avoid the incidence of side effects, topical analgesics are treatment of choice for localized muscle pain. Topical analgesics offer the potential to provide the same analgesic relief provided by oral analgesics but with minimal adverse systemic effects. The aim of this study is to present the preparation and characterization of topical analgesic gel named ＂Russian water＂. Gel is composed of Menthol, Benzocaine, Procaine HCl as topical analgesic agents indicated for temporary relief of pain. Obtained results showed prolonged analgesic effect compared with liquid ethanol solution composed of the same components.

Use of biologic agents for rheumatic diseases in pregnancy

Biologic agents have ushered a new era in the treatment of inflammatory rheumatic diseases.In recent years,several biologic agents have been approved by food and drug administration and have significantly improved outcomes for patients with immune mediatedinflammatory disorders including rheumatic and inflammatory bowel diseases.The most common used biologic therapeutic agents are tumor necrosis factor inhibitors(etanercept,infliximab,adalimumab,certolizumab pegol,and golimumab),an interleukin(IL)-6 inhibitor(tocilizumab),an IL-1 receptor antagonist(anakinra),an anti-CD-20 antibody(rituximab),and a T cell costimulation modulator(abatacept).Their use during pregnancy has been controversial because of absence of controlled studies which have enrolled pregnant women.This brief overview provides published data on use of biologic agents for the treatment of rheumatic diseases in pregnancy.

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.

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.

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.

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.

Therapeutic Efficacy Observation on Acupuncture plus Medication for Rheumatoid Arthritis

Objective： To observe the clinical efficacy of acupuncture plus medication for rheumatic arthritis （RA）. Methods： A total of 80 RA cases were randomized into an observation group and a control group, 40 in each group. Cases in the observation group received antirheumatic agents and acupuncture therapy, whereas cases in the control group received antirheumatic agents alone. The therapeutic efficacies were observed after 3 sessions of treatment. Results： After the treatment, patients in the observation group had significant improvement in their morning stiffness time, average grip of both hands, joint tenderness and joint swelling, showing statistical significances （P〈0.01）; symptoms of patients in the control group were also remarkably improved （P〈0.01, P〈0.05）. Compared with the control group, the improvements in joint tenderness and average grip of both hands in the observation group were more significant （P〈0.05）. After treatment, the Health Assessment Questionnaire （HAQ） points were significantly improved in both groups, erythrocyte sedimentation rate （ESR） and C-reactive protein （CRP） in both groups were remarkably reduced （P〈0.01, P〈0.05）; however, compared with the control group, the CRP decrease in the observation group was more significant （P〈0.05）. Conclusion： Acupuncture plus antirheumatic agents can effectively increase the RA patients＇ activities of daily living （ADL） and thus improve their quality of life.