Clinical application and prospect of novel markers of rheumatoid arthritis / 中华检验医学杂志

Rheumatoid arthritis (RA) is a chronic erosive arthritis. Early diagnosis, standardized treatment and regular monitoring of the disease will effectively mitigate disease progression and reduce the disability rate. Currently, traditional synthetic disease-modifying antirheumatic drugs (DMARDs) are used alone or in combination with new biological DMARDs or targeted synthetic DMARDS in the treatment of RA, resulting in effective remission in some refractory patients. However, the efficacy and toxicities of different treatments varies. With the development of proteomic and epigenetic technologies, some proteins, non-coding RNAs, and anti-drug antibodies (ADA) have been identified as potential markers for early diagnosis, concomitant diagnosis and disease assessment of RA. We summarized and analyzed the application prospects of novel RA diagnosis markers, including serum proteins, cell membrane proteins, non-coding RNAs, and ADA, with the aim of promoting the application of new markers that allow more precise diagnosis and treatment of RA.

Risk factors for losing hepatitis B virus surface antibody in patients with HBV surface antigen negative/surface antibody positive serostatus receiving biologic disease-modifying anti-rheumatic drugs: a nested case-control study

Abstract Background: Hepatitis B virus (HBV) reactivation consequent to immunosuppressive therapy is an increasingly prevalent problem with serious clinical implications. Treatment with biologic agents conduces to the loss of protective antibody to HBV surface antigen (anti-HBs), which significantly increases the risk of HBV reactivation. Hence, we investigated the risk factors for losing anti-HBs in patients with rheumatic diseases and HBV surface antigen negative/anti-HBs positive (HBsAg-/anti-HBs+) serostatus during treatment with biologic disease-modifying anti-rheumatic drugs (DMARDs). Methods: Using a nested case-control design, we prospectively enrolled patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis/psoriasis, or juvenile idiopathic arthritis, who were treated with biologic DMARDs at Changhua Christian Hospital, Taiwan, from January 2013 to June 2019 and had HBsAg-/anti-HBs+ serostatus; the analytic sample excluded all patients with HBsAg+ or anti-HBs- serostatus. Anti-HBs titers were monitored 6-monthly and cases were defined as anti-HBs < 10 mIU/ml during follow-up. Cases were matched one- to-all with controls with anti-HBs ≥ 10 mIU/ml on the same ascertainment date and equivalent durations of biologic DMARDs treatment (control patients could be resampled and could also become cases during follow-up). Between-group characteristics were compared and risk factors for anti-HBs loss were investigated by conditional logistic regression analyses. Results: Among 294 eligible patients, 23 cases were matched with 311 controls. The incidence of anti-HBs loss was ∼ 2.7%/person-year during biologic DMARDs treatment. Besides lower baseline anti-HBs titer (risk ratio 0.93, 95% CI 0.89-0.97), cases were significantly more likely than controls to have diabetes mellitus (risk ratio 4.76, 95% CI 1.48-15.30) and chronic kidney disease (risk ratio 14.00, 95% CI 2.22-88.23) in univariate analysis. Risk factors remaining significantly associated with anti-HBs loss in multivariate analysis were lower baseline anti-HBs titer (adjusted risk ratio 0.93, 95% CI 0.88-0.97) and chronic kidney disease (adjusted risk ratio 45.68, 95% CI 2.39-871.5). Conclusions: Besides lower baseline anti-HBs titer, chronic kidney disease also strongly predicts future anti-HBs negativity in patients with HBsAg-/anti-HBs+ serostatus who receive biologic DMARDs to treat rheumatic diseases. Patients with low anti-HBs titer (≤ 100 mIU/ml) and/or chronic kidney disease should be monitored during biologic DMARDs therapy, to enable timely prophylaxis to preempt potential HBV reactivation.

Attitudes of patients with a rheumatic disease on drug use in the COVID-19 pandemic

Abstract Background: Anti-rheumatic drugs can increase the predisposition to infection, and patients may be unaware of continuing their treatment during the COVID-19 pandemic. Objective: This study aimed to assess whether patients maintain their treatment for rheumatic conditions during the pandemic period and determine the factors responsible for discontinuation. Methods: Patients were randomly selected from the prospectively collected database of our tertiary referral center. The patients were interviewed by telephone through a standardized closed-ended questionnaire, which is targeting the continuity of the treatment plan and the considerations related to the individual choice. The patients were asked whether they hesitated to visit the hospital for follow-up or intravenous drug administration. Results: A total of 278 patients completed the questionnaire. While 62 of the patients (22.3%) had reduced or interrupted the treatment, only 11 patients (3.9%) stopped the treatment completely. A significant difference was observed between the duration of illness and the discontinuation of treatment. (p = 0.023) There was a significant difference in disease activity between the group that stopped treatment and continued treatment. (p = 0.001) There was no statistically significant difference in other demographic characteristics. One hundred thirty-five patients (48.6%) made the treatment decision by themselves, and 80% continued the treatment. Reasons for stopping the treatment were anxiety (48.4%), not being able to go to the hospital for intravenous treatment (45.1%), and not being able to find the drug (6.5%). Conclusion: Since patients with long-term illnesses were found to be significantly more likely to stop their treatment, this group of patients should be monitored.

Prescribing pattern and adverse drug effects monitoring of anti-rheumatoid drugs in rheumatoid arthritis patients in a tertiary care hospital

Background: Rheumatoid arthritis (RA) is a common disease that causes substantial morbidity in most patients and premature mortality in many. All the drugs used in the treatment of rheumatoid arthritis show significant toxicity and hence it is important to monitor the drugs for adverse drug reaction. This study will estimate the prescribing pattern and bring out the possible adverse drug reactions in patients with rheumatoid arthritis.Methods: This study included 200 patients with rheumatoid arthritis who fulfilled the study criteria were observed for three months. Their prescriptions were collected and analysed. The symptoms of adverse drug reaction were documented through questionnaire. The causality assessment was done by WHO-UMC assessment scale and severity by using modified Hartwig-Seigel severity assessment scale.Results: This study showed most of the patients were female (86%). Majority of them were in age group of 51-60 years. Average number of drugs per prescription was 10.57. Out of 200 patients, 2% were on single DMARD and 50.5% were on two DMARDs. 40% and 7.5% were taking three and four DMARDs respectively. A total of 450 adverse drug reactions were reported, out of which 68.4% due to steroid,12.5% due to DMARDs and 19.1 due to use of NSAIDs, DMARDs and glucocortisteroids. Chloroquine maculopathy occurred in 3 patients and elevated liver enzymes due to methotrexate in 3 patients, which necessitated DMARD withdrawal. Most patients had 1-3 ADRs. 6% of ADRs were severe and 54% belongs to probable category of causality assessment.Conclusions: Treatment of rheumatoid arthritis is mainly based on DMARDs, glucocorticosteroids and NSAIDs. So, occurrence of ADR is much common. Proper monitoring of therapy and timely modification of drugs and lifestyle can reduce the ADR occurrence.

Effectiveness and Safety of Tacrolimus in Patients with Active Rheumatoid Arthritis with Inadequate Response to Disease-modifying Anti-rheumatic Drugs: The TREASURE Study

OBJECTIVE: Evaluate effectiveness/safety of tacrolimus in patients in Korea with active rheumatoid arthritis (RA) and unsuccessful response to disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Open-label, single-arm, non-comparative, 24-week, Phase-IV study in patients with active RA who had taken DMARDs for >6 months. Following a washout period, tacrolimus was initiated (baseline-12 weeks; dose 2 mg/day and 1.5 mg/day in patients aged ≤65 and >65 years, respectively). After 12 weeks, dose could be adjusted (remaining between 1~3 mg); treatment continued to 24 weeks. Primary endpoint was American College of Rheumatology 20% improvement (ACR20) (baseline-Week 24). Secondary endpoints included ACR50/ACR70 response, disease-activity score in 28 joints (DAS28) erythrocyte sedimentation rate (ESR), number of tender/swollen joints, and bone mineral density (BMD) loss. Adverse events (AEs) were recorded. RESULTS: Overall, 121 patients were analysed. Mean±standard deviation tacrolimus dose baseline-Week 24 was 1.81±0.47 mg/day. After 24 weeks, 64.5%, 39.7%, and 19.0% of patients were ACR20, ACR50, and ACR70 responders, respectively. DAS28-ESR score decreased from 5.5±0.8 (baseline) to 3.7±1.5 (Week 24; p < 0.0001); number of tender/swollen joints decreased. Between screening and Week 24, change in BMD-T score in lumbar and femur regions was −0.06±0.38 (p=0.1550) and −0.04±0.28 (p=0.0936), respectively, with no significant change in International Society for Clinical Densitometry classification. Fifty-six (46.3%) patients experienced 93 AEs; 75.3% were mild. No unexpected safety signals identified. CONCLUSION: Tacrolimus therapy was associated with a high proportion of ACR responders, and improved DAS28-ESR score and physical joint function during the study. Tacrolimus may be a suitable therapy for DMARD-resistant patients with RA.

Advance in drug treatment of autoimmune diseases / 中国药理学通报

Autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, etc.) are diseases characterized by local or systemic abnormal inflammatory immune response. At present, the treatment drugs of autoimmune diseases mainly include nonsteroid anti-inflammatory drugs, steroid anti-inflammatory drugs and disease modifying anti-rheumatic drugs (chemical medicine, natural medicine and biological agents), etc. With the pathological mechanism of autoimmune diseases to be clarified deeply and the discovery of new drug targets, new biological agents targeting cytokines and cell surface molecules have been developed rapidly. In recent years, multiple small molecule drugs targeting Janus kinase/ signal transducers and activators of transcription signaling pathway have been developed and applied in clinic. Soft regulation of inflammatory immune response drugs are the drugs with anti-inflammatory and immunomodulatory effects, as well as less adverse reactions. To develop this type of drug will be a new strategy and one of the main directions for the treatment of autoimmune diseases. The research progress of medicines to treat autoimmune diseases has been reviewed in this paper.

Clinical deep remission and related factors in a large cohort of patients with rheumatoid arthritis / 中华医学杂志(英文版)

Background:@#Clinical remission is the treatment target in rheumatoid arthritis (RA). This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA.@*Methods:@#This study composed of 342 patients with RA. Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016. The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site. Subsequently, patients fulfilled remission criteria were further analyzed. The practicability of different definitions of remission of RA was rated by a panel of rheumatologists. Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months.@*Results:@#In this cohort of 342 patients with RA, the proportions of patients achieving remission were 38.0%, 29.5%, 24.9%, 21.1%, 19.0%, 18.1%, and 17.0%, based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP), DAS28 using ESR (DAS28-ESR), routine assessment of patient index data 3 (RAPID-3), Boolean, simplified disease activity index (SDAI), clinical disease activity index, and the newly described clinical deep remission (CliDR), respectively. Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0, respectively). Compared with the non-sustained intensive group, sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%, 23.8%, and 21.3% in patients with RA based on Boolean (χ2=3.937, P=0.047), SDAI (χ2=4.666, P=0.031), and CliDR criteria (χ2=4.297, P=0.038). The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide, followed by methotrexate, and hydroxychloroquine. Compared with the non-remission group, patients achieving remission had a longer median duration of DMARDs (45.0 [22.8–72.3] months, Z=-2.295, P=0.022).@*Conclusions:@#The findings in this study indicated that clinical deep remission is achievable in patients with RA. Sustained intensive DMARD treatment is needed to achieve a better outcome in RA.

Active surveillance of adverse drug reactions in patients with rheumatoid arthritis in a tertiary care teaching hospital

Background: Drugs used in the treatment of rheumatoid arthritis show significant toxicity and morbidity. The objective of the study was to evaluate the nature and incidence of adverse drug reaction in patients with rheumatoid arthritis on anti-rheumatic drugs and to assess the causality and severity of the documented adverse drug reactions.Methods: The prospective observational study was done for two months in rheumatology outpatient department. All patients were interviewed for basic details, treatment history and adverse drug reactions and were recorded. Causality assessment and severity assessment of the recorded adverse drug reactions were done.Results: About 283 patients attended the rheumatology out-patient department during the two months period out of which 57 patients had one or more adverse drug reaction. The incidence of adverse drug reaction observed in rheumatology out-patient department to anti rheumatic drug was 20.14%. A total of 145 adverse drug reactions were noted in 57 patients. The most common adverse drug reaction reported was epigastric pain (6.89%) followed by headache and dyslipidemia (6.25%). The most common system associated with adverse drug reaction was gastrointestinal system (29.66%) followed by central nervous system and cardiovascular system (15.86%). Reported adverse drug reactions were assessed for causality and maximum belonged to probable (66.9%). Severity assessment revealed that most of the adverse drug reactions were mild (74.48%) in nature.Conclusions: Active surveillance for adverse drug reactions to anti rheumatic drug in patients with rheumatoid arthritis will allow early detection of adverse drug reactions and timely intervention to provide maximum benefit to the patients.

A cost-effective analysis of various disease modifying anti-rheumatic drugs for patients with Rheumatoid Arthritis

Background: Rheumatoid Arthritis (RA) is a chronic disabling disorder that lowers quality of life in the affected patients. Early treatment with disease-modifying anti-rheumatic drugs (DMARDs, provides better control of disease and minimize joint destruction. Long term therapy imparts considerable economic burden to the patients. Cost effective analysis was performed among the patients treated with methotrexate (MTX) alone, hydroxychloroquine (HCQ) alone, and both (MTX+HCQ).Methods: A prospective, observational study for six months to analyze the cost-effectiveness in RA patients with DMARDs-MTX, HCQ and MTX+HCQ. A total of 91 patients were included for analysis; 43 patients in MTX and HCQ group; 37 patients in MTX group and 11 patients in HCQ group. To assess the functional disability,” Stanford Health Assessment Questionnaire - Disability Index” (HAQ-DI) was administered. The patients were followed up for four months. The HAQ-DI at the baseline was compared with that of final follow up. The change in HAQ-DI and the total costs were used to find out the average cost- effective ratio (ACER).Results: The least ACER was obtained for Hydroxychloroquine and highest was for Methotrexate. But there was no statistically significant difference in ACER between various treatment groups. There was no significant difference in the disease activity improvement between the three groups.Conclusions: MTX, HCQ and MTX+HCQ showed improvement in disease activity without any significant difference. MTX is superior considering direct cost but there is no difference in the total cost between three groups.

Enfermedad de Still del Adulto, a propósito de un caso / Still's disease, a clinical case

La enfermedad de Still del Adulto es una variante sistémica del universo llamado "artritis idiopática juvenil", cuya diferencia es la edad de aparición, recibiendo este nombre cuando el cuadro se manifiesta en personas mayores de 15 años. Es una enfermedad autoinflamatoria caracterizada por fiebre intermitente, artritis, rash evanescente y linfadenopatías, asociado a manifestaciones de compromiso sistémico. Es una patología de baja prevalencia, pero es importante considerarla como uno de los principales diagnósticos etiológicos de la fiebre de origen desconocido.

Adult-onset Still's disease is a systemic variant of Still's disease distinguished from juvenile idiopathic arthritis by its onset age of over 15. It is an auto-inflammatory disease characterized by intermittent fever, arthritis, short-lived rash and lymphadenopathies. It has low prevalence but is important to consider as one of the principle etiological diagnoses of fever of unknown origin.

Infecciones severas en pacientes con artritis reumatoide tratados con fármacos antagonistas del factor de necrosis tumor alfa / Serious infections in patients with rheumatoid arthritis treated with tumor necrosis factor alpha antagonist therapy

ResumenJustificación y objetivos:el uso de fármacos antagonistas del factor de necrosis tumoral alfa se asocia a infecciones severas en artritis reumatoide, con una alta morbi-mortalidad en la práctica clínica. No existe casuística publicada respecto al tema en nuestro país. Se pretende aportar información relacionada con la epidemiología local de las infecciones severas e identificar factores de riesgo asociados.Métodos:estudio observacional retrospectivo, que incluyó 50 pacientes tratados al menos un año en el periodo 2006-2012. Se evaluaron las características demográficas, así como las clínicas y epidemiológicas de la(s) infección(es) severa(s) desarrollada(s) y los factores de riesgo asociados.Resultados:la mayor parte de los pacientes fueron mujeres en edad media. Solo se documentó una infección severa, que correspondió a una infección de piel y tejido blando que resolvió con terapia antibiótica intravenosa. Se registraron factores de riesgo, especialmente en uso de terapia inmunosupresora esteroidal y el antecedente quirúrgico reciente, con una baja prevalencia de comorbilidades.Conclusiones:el perfil demográfico, así como el perfil clínico de las infecciones severas es similar a otras poblaciones, la baja incidencia de éstas en la cohorte podría relacionarse a una menor prevalencia de comorbilidades, no obstante se requiere investigaciones futuras para corroborar o descartar dicha observación.

AbstractAim and objetives:the use of tumour necrosis factor alpha therapy antagonist leads to an increased risk of serious infections in rheumatoid arthritis, with a high morbi-mortality in clinical practice. There are no published data in our country. This study pretends to provide knowledge about the local epidemiology of serious infections and to identify associated risk factors.Methods:An observational and retrospective study, included 50 patients treated at least for one year between 2006-2012. Demographic characteristics, clinical and epidemiological characteristics of serious infections and risk factors associated with serious infections were described.Results:A predominant female population in middle age was detected. Just one serious infection was described, corresponding to serious skin and soft tissue infection that resolved with intravenous antibiotics. Risk factors were described including inmunosuppresive therapy with steroids and prior surgery.Conclusions:Demographic profile of analized population and their clinic profile of serious infectios are similar to others populations. Low incidence of serious infections in this cohort could be related with less comorbilities than others populations, although, this topic needs further investigations to corroborate or discard this observation.

Prevalence of Rheumatoid Arthritis patients in Adults: A Hospital Based Study

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by a symmetrical inflammation of the synovium, resulting in tenderness and destruction of bone and cartilage in various joints, particularly the smaller joints of the hands and feet. Although the cause of RA is unknown, autoimmunity plays a pivotal role in its chronicity and progression. RA affects approximately 1.0% of the general population, women more often than men, and the inflammatory burden of the disease results in functional disability. Methods: Forty patients were included in this study. The case control study was carried out in the Department of Orthopaedics, Geetanjali Medical college and Hospital, Udaipur. Duration of this study was six month. Results: In the present study, forty patients were included, out of which 15% male and 85% female. From the forty patients most of the people were belongs to 41-50 age group followed by 51-60 (27.5%) ,35-40 (25%) ,61-65(17.5%). Elevated ESR were in the 52.5% of group, rest of the people were normal. Same as in case of CRP positive found in the 52.5% & 47.5% were negative. Conclusion: The prevalence in RA group quite high as compared to general population.

Severe infection in patients with rheumatoid arthritis taking anakinra, rituximab, or abatacept: a systematic review of observational studies / Infecções graves em pacientes com artrite reumatoide em uso de anakinra, rituximab ou abatacept: revisão sistemática de estudos observacionais

ABSTRACT A question is raised about an increased risk of severe infection from the use of biological drugs in patients with rheumatoid arthritis. This systematic review of observational studies aimed at assessing the risk of severe infection associated with the use of anakinra, rituximab, and abatacept in patients with rheumatoid arthritis. The following databases were searched: PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo, and Lilacs up to July 2010. Severe infections were defined as those life-threatening ones in need of the use of parenteral antibiotics or of hospitalization. Longitudinal observational studies were selected without language restriction, involving adult patients diagnosed with rheumatoid arthritis and who used anakinra, rituximab, or abatacept. In four studies related to anakinra, 129 (5.1%) severe infections were related in 2896 patients, of which three died. With respect to rituximab, two studies reported 72 (5.9%) severe infections in 1224 patients, of which two died. Abatacept was evaluated in only one study in which 25 (2.4%) severe infections were reported in 1046 patients. The main site of infection for these three drugs was the respiratory tract. One possible explanation for the high frequency of severe infections associated with anakinra may be the longer follow-up time in the selected studies. The high frequency of severe infections associated with rituximab could be credited to the less strict inclusion criteria for the patients studied. Therefore, infection monitoring should be cautious in patients with rheumatoid arthritis in use of these three drugs.

RESUMO Existe um questionamento sobre aumento do risco de infecções graves pelo uso de medicamentos biológicos por pacientes com artrite reumatoide. Esta revisão sistemática de estudos observacionais objetivou avaliar o risco de infecções graves associadas ao uso de anakinra, rituximab e abatacept em pacientes com artrite reumatoide. Foram pesquisadas as bases PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo e Lilacs até julho/2010. Infecções graves foram definidas como aquelas com de risco de vida, necessidade de antibióticos parenterais ou de hospitalização. Foram selecionados estudos observacionais longitudinais, sem restrição de idioma, que envolviam pacientes adultos com diagnóstico de artrite reumatoide que usaram anakinra, rituximab, abatacept. Em quatro estudos relacionados ao anakinra, foram relatadas 129 (5,1%) infecções graves em 2.896 pacientes, dos quais três evoluíram para óbito. Sobre o rituximab, dois estudos relataram 72 (5,9%) infecções graves em 1.224 pacientes, dos quais dois evoluíram para óbito. O abatacept foi avaliado em apenas um estudo, no qual foram relatadas 25 (2,4%) infecções graves em 1.046 pacientes. O principal sítio de infecção para os três medicamentos foi o trato respiratório. Uma possível explicação para a frequência elevada de infecções graves associadas ao anakinra pode ser o maior tempo de acompanhamento nos estudos selecionados. A frequência elevada de infecções graves associadas ao rituximab poderia ser creditada ao critério menos restrito de inclusão de pacientes. Portanto, deve ser cautelosa a monitoração de infecções nos pacientes com artrite reumatoide que usam esses três medicamentos.

Pharmacognostic and phytopharmacology study of Anacyclus pyrethrum: An insight.

Anacyclus pyrethrum an amazing medicinal plant is one of the most widely growing species of the family Asteraceae. The present review endow with significant information about its phytochemical investigations, pharmacological activities and medicinal properties as a folk medicine to treat several disease like anti-rheumatic, analgesic, antibacterial, antiviral, carminative, anti-catarrh, improve digestion, emmenagogue, febrifuge, nervine, vermifuge, and sialagogue. The plant has been reported several pharmacological actions such as antidiabetic, immunostimulating effect, inhibitory effects, antidepressant activity, anticonvulsant activity, memory-enhancing activity, aphrodisiacs, antimicrobial activity, antioxidant, local anesthetic effect, insecticidal effect, action on COX and LOX, interactions with testosterone, interaction with libido, and it interaction with testicles. Mainly the root portion has beneficial properties that can serve the mankind. The entire plant can be extensively studied for further future prospective.

The specialist physician's approach to rheumatoid arthritis in South Africa

Rheumatoid arthritis (RA) is expected to increase in Africa and South Africa. Due to the low numbers of rheumatologists in South Africa, specialist physicians also have to care for patients with RA. Furthermore several new developments have taken place in recent years which improved the management and outcome of RA. Classification criteria were updated, assessment follow-up tools were refined and above all, several new biological disease-modifying anti-rheumatic drugs were developed. Therefore it is imperative for specialist physicians to update themselves with the newest developments in the management of RA. This article provides an overview of the newest developments in the management of RA in the South African context. This approach may well apply to countries with similar specialist to patient ratios and disease profiles.

Analysis of Drug Utilization for Patients with Ankylosing Spondylitis

BACKGROUND & OBJECT: Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes ankylosis and deformation of axial joints. Since current medicine cannot cure the disease yet, alleviating pain and preventing deformation with medications are the main therapy for patients with AS. The key medications for these purposes include nonsteroidal anti-inflammatory drugs (NSAIDs), and tumor necrosis factor-alpha (TNF-alpha) inhibitors. This study aims to analyze prescribing patterns of AS patients in South Korea. METHOD: National Patients Sample data compiled by the Health Insurance Review and Assessment Service from 2013 was analyzed. Patients with AS were identified with Korean Standard Classification of Diseases code-6, which was M45. The rates of prescription, discontinuation, and switching ingredients were calculated for each medication during 2013. RESULTS: Total number of patients was 655, and most of them were male (n = 514, 78.5%). Of all age groups, the proportion of 30-40 year old patients was the greatest (35.1%). The most utilized drug class was NSAIDs (82.4%). Less than half of patients were prescribed TNF-alpha inhibitors (n = 212, 32.4%). Meloxicam, aceclofenac, and celecoxib were the most frequently prescribed NSAIDs. In case of TNF-alpha inhibitors, adalimumab, etanercept and infliximab were the top three most prescribed drugs. Although not recommended by the current practice guideline, significant proportions of patients were identified using disease modifying anti-rheumatic drugs (DMARDs). CONCLUSION: Considering the current practice guideline and previous studies about the efficacy, the use of DMARDs should be reduced and medical insurance term in South Korea should be re-examined.

Reactivation of Hepatitis B Virus in Patients with Rheumatologic Disease Treated with Biologic Disease Modifying Anti-rheumatic Drugs: Screening and Treatment

Reactivation of hepatitis B virus (HBV) is not infrequently reported in patients with rheumatologic diseases treated with biologic disease modify anti-rheumatic drugs (DMARDs) such as a tumor necrosis factor-alpha inhibitor or a B cell depleting molecule. HBV reactivation is reported not only in patients with chronic hepatitis B but also in cases with resolved HBV where HBsAg is negative and anti-HBc positive. Studies suggest that with treatment using biologic DMARDs, the risk of HBV reactivation increases when HBsAg is positive independent of HBV DNA replication status, and in those with anti-HBc positive and serum HBV DNA positive. Therefore, testing for HBsAg as well as anti-HBc is important before initiating treatment with a biologic DMARD. In addition, evaluation of serum HBV DNA may be required when either HBsAg or anti-HBc turns out to be positive. Although series of reports suggest that prophylactic antiviral therapy in patients with higher risk of HBV reactivation would diminish morbidity and mortality from hepatic cause, solid guidelines pertaining to when to initiate and terminate HBV antiviral therapy and which agent should be used should be provided in the future.

Effect of Combination Therapies with Methotrexate, Sulfasalazine and Hydroxychloroquine on Hyperlipemia of Rheumatoid Arthritis / 昆明医科大学学报

Objective To observe the effect of combination therapies with methotrexate, sulfasalazine and hydroxychloroquine on hyperlipemia of rheumatoid arthritis.Method From 2009 November to 2010 November, 68 RA inpatients and outpatients in the department of rheumatism of our hospital were randomly divided into two groups: A group and B group, 34 cases in each group. The patients in A group were given combination of methotrexate, sulfasalazine, hydroxychloroquine sulfate for the treatment of RA,patients in B group, based on A group's treatment, were treated by xuezhikang. Some indexes were observed in two group before treatment and 6 months after treatment, including cholesterolTC,low density lipoprotein cholesterol LDL-C , triglyceride TG , high density lipoprotein cholesterol HDL-C , swelling index, joint pain index, time of morning stiffness, C-reactive protein CRP , erythrocyte sedimentation rate ESR and DAS28. Results After 6 months’ treatment, the serum levels of TC, TG,, LDL-C, both in two groups of patients, were lower than those before treatment, and HDL-C was higher than that before treatment, there were significant differences (P0.05) . Conclusion RA patients have abnormal blood lipid levels, disease-modifying anti-rheumatic drugs have effect on blood lipid during remission joint disease in RA patients.

A Case of Rheumatoid Arthritis in a Patient with Bruton-Type Agammaglobulinemia

Bruton-type agammaglobulinemia is primary hypogammaglobulinemia followed by severe recurrent infection, including bacterial otitis media, bronchitis, pneumonia, and meningitis. Septic arthritis is a main musculoskeletal disorder that can occur in association with Bruton-type agammaglobulinemia. But the development of rheumatoid arthritis (RA) is rarely reported in a patient with hypogammaglobulinemia. Here, we describe a case of 34-year-old male with Bruton-type agammaglobulinemia, who presented with multiple symmetric polyarthritis. He was diagnosed as having a RA according to ACR criteria. His symptoms of polyarthritis had been improved after the introduction of medications including DMARDs (disease modifying anti-rheumatic drugs). Our case suggests that RA can be developed in the setting of agammaglobulinemia, and even in this situation, anti-rheumatic agents were effective to control arthritis without complication such as severe infection.

Estudos observacionais de infecções graves em artrite reumatoide: Uma revisão sistemática de medicamentos biológicos não anti-tnf-alfa / Observational studies of serious infections in rheumatoid arthritis: A systematic review of biological medicines not anti-TNF-alpha

Introdução. A segurança do emprego de Disease-Modifying Antirheumatic Drugs (DMARDs) biológicos não antagonistas do fator de necrose tumoral (TNF) em pacientes com artrite reumatóide ainda não está plenamente estabelecida. Evidências do risco de infeccções graves associado a estes medicamentos descritas por meio de relatos de casos ou ensaios clínicos não foram ainda extensivamente documentadas previamente em revisão de estudos mais longos. Objetivo. Avaliar o risco de infecções graves associado ao uso de DMARDs biológicos não anti-TNF (anakinra, rituximab, abatacept e tocilizumab) em pacientes com AR utilizando exclusivamente estudos observacionais. Método. Revisão sistemática (RS) de estudos observacionais utilizando as principais bases de dados bibliográficas para a busca de artigos publicados até julho de 2010 para avaliar o risco de infecções graves nos pacientes com AR que fizeram uso de anakinra, rituximab, abatacept e tocilizumab...

Resultados. Foram relatados em quatro estudos de 12 a 36 meses de acompanhamento relacionados ao anakinra 129 (5,1 por cento) infecções graves em 2.896 pacientes dos quais três evoluíram para óbito. Em relação ao rituximab, dois estudos relataram 72 infecções graves (5,9 por cento) em 1.224 pacientes (incluindo diabéticos e aqueles que usavam quaisquer DMARDS sintéticos) dos quais dois evoluíram para óbito. O abatacept foi avaliado em apenas um estudo de seis meses de duração no qual foram relatadas 25 infecções graves (2,4 por cento) em 1046 pacientes. Não foi selecionado nenhum estudo referente ao tocilizumab. O principal sítio de infecção para conjunto dos três medicamentos foi o trato respiratório. Conclusões. As freqüências maiores que 5 por cento de infecções graves detectadas no contexto do uso destes medicamentos são classificadas como eventos adversos “comuns”. Cautela na monitorização destes pacientes, principalmente diabéticos, devem ser tomadas considerando que estas incidências foram maiores que as divulgadas em revisões recentes baseadas em ensaios clínicos...