Combination Disease-modifying Antirheumatic Drugs Therapy Research Articles

Pharmacological Approaches in Rheumatoid Arthritis- An In-depth Analysis of Prescribed Medications

Inflammation, pain, swelling, and stability of the joints are some of the symptoms associated with rheumatoid arthritis (RA). A variety of treatment options are available to manage symptoms and slow the progression of RA, despite the fact that there is no cure. This cross-sectional study, which was conducted in a tertiary care hospital in Kerala, India, aimed to evaluate medication prescribing practices and therapeutic strategies in RA patients. The study included 280 RA patients and data on demographics, medications prescribed, dosage, and mode of administration were collected. The findings revealed that disease-modifying anti-rheumatic drugs (DMARDs) were the cornerstone of RA treatment, with hydroxychloroquine (HCQ), methotrexate (MTX), and sulfasalazine (SAAZ) being the most frequently prescribed DMARDs. Combination DMARD therapy, particularly the triple combination of HCQ + Folitrax + SAAZ, was prevalent among patients. Furthermore, the study highlighted the use of biologic DMARDs, such as rituximab and tofacitinib, albeit at a relatively lower rate due to the outpatient population’s milder disease severity. Supplement therapy, including vitamin D3 and folic acid, was commonly prescribed to address deficiencies and mitigate the side effects of medications like MTX. The prescription patterns also encompassed analgesics, anti-anxiety, and antidepressant medications to manage pain and psychological symptoms associated with RA. Steroids were administered initially to control inflammation, with a focus on minimizing long-term usage. The study underscores the complexity of RA management and the importance of individualized treatment approaches. It highlights the evolving landscape of RA therapeutics, emphasizing the need for clinicians to stay updated on emerging evidence and guidelines. Future research should focus on evaluating the long-term efficacy, safety, and cost-effectiveness of different treatment regimens to optimize patient outcomes in RA management.

Real-world Comparative Effectiveness of Methotrexate-based Combinations for Rheumatoid Arthritis: A Retrospective Cohort Study

Guidelines recommend using disease-modifying antirheumatic drugs (DMARDs) in combination with methotrexate (MTX) for patients with rheumatoid arthritis (RA) after monotherapy. Little is known about the real-world comparative effectiveness of these MTX-DMARD combinations. This study compared the effectiveness of various MTX-based DMARD combinations for patients with RA initiating MTX-DMARD combination therapy using administrative claims database. This retrospective cohort study included adults (aged ≥18 years) with RA who initiated MTX combination treatment with conventional synthetic DMARDs (csDMARDs), tumor necrosis factor inhibitor (TNFi) biologic DMARDs (bDMARDs), non-TNFi bDMARDs, or targeted synthetic DMARDs (tsDMARDs) between July 1, 2012, and December 31, 2013 (index date), from the MarketScan Commercial Claims Data. Patients had continuous enrollment from the 6 months of preindex period until the 12 months of postindex period. The MTX-based DMARD combination therapy cohort was defined as ≥1 MTX prescription in the first 30 days from the index date and ≥14 days overlapping use of the prescription fills of the MTX and the index DMARD. Effectiveness was measured by using the claims algorithm (dosing, switching, addition, oral glucocorticoid use, or multiple glucocorticoid injection). Propensity score analysis with the inverse probability of treatment weighting (PS-IPTW), estimated by using the generalized boosted machine learning method, was used to balance the distribution of baseline variables between the combination groups. Multivariable logistic regression using PS-IPTW was conducted to compare the effectiveness of the combination groups. Sensitivity analysis evaluated the modified effectiveness algorithms or the time to the first treatment failure. A total of 3174 adult patients with RA starting an MTX-DMARD combination therapy were identified (mean [SD] age, 50 [9] years), including 1568 (49%) initiating a csDMARD+MTX, 1343 (42%) initiating TNFi+MTX, and 240 (8%) initiating non-TNFi bDMARD+MTX, and 23 (1%) initiating tsDMARD+MTX. Owing to the small sample, the tsDMARD combination group was not included in the comparative analysis. Algorithm-based therapy effectiveness was found in 9.95% of the csDMARD+MTX, 20.48% of the TNFi+MTX, and 20.83% of the non-TNFi+MTX groups. PS-IPTW showed that the csDMARD combination is less effective (adjusted odds ratio, 0.422; 95% CI, 0.341-0.524) than the TNFi combination; however, the non-TNFi biologic combination had similar effectiveness (aOR, 1.063; 95% CI, 0.680-1.662) compared to the TNFi combination. Sensitivity analyses confirmed the main results. Among RA patients initiating MTX-DMARD combinations, both non-TNFi biologics and TNFi-based combinations with MTX were equally effective, but csDMARD+MTX was less effective than the TNFi plus MTX.

Risk of incident cardiovascular events with disease-modifying anti-rheumatic drugs among adults with rheumatoid arthritis: a nested case-control study.

This study examined the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). This nested case-control study used the MarketScan database (2012-2014), involving adult RA patients (aged ≥18 years) initiating either a conventional synthetic (cs) DMARD, biologic DMARD, or targeted synthetic (ts) DMARD between January 1, 2013 and December 31, 2014 (cohort entry) and had no CVD history. Cases were individuals with incident CVD identified using diagnosis codes or procedure codes from medical claims. For each case, 10 age- and sex-matched controls were selected using the incident density sampling with replacement. Prescriptions of DMARDs were measured 90 days before the event date. Conditional logistic regression examined the association of risk of CVD with DMARDs in combination treatment or individual use, with reference to methotrexate (MTX) monotherapy, adjusting for baseline confounders. Subgroup analyses were performed separately in DMARD combination therapy users or individual DMARD users, respectively. In total, 270 cases of incident CVD and 2700 controls were included (mean [standard deviation (SD)] age: 54[1]; 75.6% women). The commonly prescribed DMARD therapies were csDMARD monotherapy (n = 795, 27.04%), followed by tumor necrosis factor inhibitors (TNFi) monotherapy (n = 367, 12.48%), and TNFi in combination with MTX (n = 314, 10.68%). Compared with MTX monotherapy, overall use of DMARD agents was not associated with the differential risk of CVD, including various types of DMARD combination regimens. The findings were similar across subgroup analyses. The study found no differential risk of CVD with DMARDs in combination therapy or monotherapy compared to MTX monotherapy in patients with RA. Key Points • This study evaluated the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). • Findings suggest no differential CVD risk with DMARDs in combination with MTX or used individually compared with MTX monotherapy in patients with early RA. • Further efforts should focus on a better understanding of the mechanism of DMARD combination treatments with MTX in modifying CV risk.

AB0244 MEDICATION ADHERENCE AND BELIEFS ABOUT MEDICATION IN PATIENTS WITH RHEUMATOID ARTHRITIS.

BackgroundConsistent immunosuppressive treatment of rheumatoid arthritis (RA) with disease-modifying anti-rheumatic drugs (DMARDs) is crucial for reduced progression and improved long-term outcome of the disease. Therefore, drug adherence is a prerequisite, which is often insufficient according to literature.ObjectivesOur aim was to investigate the relationship between adherence and beliefs about medication in patients with RA.MethodsThe study included 137 RA patients (102 female, 35 male; age range 28-86 years, Ø 64.8 ± 12.6 yrs; SDAI Ø 9.9 ± 6.8; 61 % DMARD monotherapy, 31 % DMARD combination therapy, 9 % currently treated without DMARD). Medication adherence was measured with the Compliance-Questionnaire-Rheumatology (CQR). This is a self-report questionnaire with 19 items (4 response options each). The sum score is mapped to a scale from 0 to 100 % (CQR%), where 100 % corresponds to optimal adherence. A CQR% ≥ 80 % was defined as satisfactory adherence. In addition, the specific part of the Beliefs about Medicines Questionnaire (BMQ) was used to assess patients’ opinions about the necessity of their medication therapy and their concerns. Besides correlation analyses (Spearman-Rho) multiple linear regression was applied to determine factors influencing adherence (coefficient of determination: adjusted R2).ResultsAdherence was satisfactory in 93 RA patients (67.9 %) and insufficient in almost one-third (n = 44, 32.1 %). Analyses showed that adherence was significantly related to belief in necessity (r = 0.46; p < 0.001) and concerns about drug therapy (r = -0.27; p = 0.001). Furthermore, it became apparent that adherence is closely linked to the age of the patient (r = 0.30; p < 0.001). Younger RA patients (< 60 yrs) had significantly lower CQR%-scores than older RA patients (≥ 60 yrs; p < 0.01). Belief in the necessity of therapy, medication concerns and patient age accounted for almost half of the patient-specific variability in adherence (each p < 0.001; R2 = 42.9 %), suggesting a strong dependence of adherence on these three factors.ConclusionAdherence is insufficient in about one-third of RA patients. Additionally, adherence appears to be strongly dependent on the patient’s belief in the necessity of therapy, medication concerns and age. Physicians should strive for all RA patients to have sufficient knowledge about their medication, strengthen the belief in the necessity of the therapy and be mindful of adherence when talking to patients.Disclosure of InterestsNone declared

Psychological impact of coronavirus disease 2019 pandemic on patients with rheumatological disorders: A web-based cross-sectional multicentric survey

Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in uncertainty and negative psychological outcomes for patients with autoimmune rheumatic diseases for several reasons. It is essential to understand the level of anxiety among rheumatic disease patients at the current situation of COVID-19.Objectives and Methods: A web-based cross-sectional multicenter survey was done across 5 rheumatology centers in India. The study duration was between 9th May and May 16, 2020. The questionnaire included consent, demographic details, medication history, opinion about tele rheumatology services, and anxiety score measured by Beck Anxiety Inventory.Results: The survey was sent to 2987 patients, there were 933 responses, and 581 were complete (male = 175). Complete responses were considered for data analysis. Rheumatoid arthritis was the most frequent (50.6%) diagnosis followed by other conditions. Most of the patients (43%) were on combination disease-modifying anti-rheumatic drug therapy, 12.7% of patients were on biological drugs, and 23.9% of patients were on glucocorticoids (GCs). Statistically significant higher anxiety scores were observed in females (8.79 ± 9.3), fibromyalgia patients (19.78 ± 14.8), patients on GCs (9.26 ± 8.8), and biological agents (10.65 ± 10.6). Difficulty in meeting rheumatologists and getting medications was expressed by 327 (56.2%) and 73 (29.7%) respondents, respectively.Conclusion: The findings of the study revealed that anxiety is a major concern in patients with autoimmune rheumatic diseases. Fibromyalgia patients and those who were on GC and biological drugs were found to have more anxiety levels compared to other groups of patients. There is a need to intensify the awareness and address the mental health issues.

EP14 Association between initial csDMARD strategy and disease activity at 6 months in patients with new onset rheumatoid arthritis

Abstract Background Until 2018, NICE guidance recommended the use of a combination of disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate (MTX), in the initial management of people with rheumatoid arthritis (RA). In 2018 the guideline was updated to recommend monotherapy with MTX due to uncertainties in the evidence for combination therapy. However, it remains a requirement for progression onto any biologic that the patient should have persistent high disease activity and/or have intolerance to, a minimum of two DMARDs. The aim of this study was to understand the association between initial treatment strategy and EULAR response at 6 months. Methods This analysis included patients recruited to the longitudinal observational Rheumatoid Arthritis Medication Study (RAMS) in the UK who were DMARD naïve and had symptoms for less than 1 year. Patients were defined as either starting MTX monotherapy or MTX in combination with another DMARD (6 weeks either side of MTX start date) and categorised into EULAR non responders or moderate/ good responders after 6 months. A logistic regression model was applied to test the association between initial treatment strategy and EULAR response at 6 months, adjusting for confounders. Results A total of 948 participants were included in the analysis. MTX monotherapy was prescribed in 72% (n = 678) of patients and combination therapy was prescribed in 28% (n = 270) of patients, the majority of whom received MTX plus hydroxychloroquine (HCQ) (n = 236, 87%). There was no significant difference between the MTX monotherapy and combination therapy groups in EULAR response at 6-months (adjusted odds ratio [aOR] 0.77, 95% CI 0.53 to 1.14). Conclusion In this large UK observational study investigating the effect of treatment strategy within the first 6 weeks of presentation and treatment response at 6 months, there was no significant difference between combination DMARD therapy and MTX monotherapy on EULAR response. Most patients received MTX in combination with HCQ, for which little evidence exists. Disclosures S. Wood None. K. Hyrich Consultancies; ABBVIE. Grants/research support; BMS, PFIZER, UCB. S. Verstappen None. D. Steinke None.

Myeloid-related proteins 8/14 failed to act as theragnostic biomarker in axial spondyloarthritis patients on combination disease-modifying anti-rheumatic drugs therapy

Background: Reports signifying the utility of myeloid-related proteins (MRP) 8/14 in axial spondyloarthritis (AxSpA) as a theragnostic biomarker are scarce. Objectives: Evaluating the utility of serum MRP 8/14 (baseline levels and change from baseline to 3 months) in AxSpA as a predictor of Assessment of SpondyloArthritis International Society (ASAS) 20 response at 6 months post combination disease-modifying anti-rheumatic drugs (DMARD) therapy. Methods: Serum MRP 8/14 was assayed using enzyme-linked immunosorbent assay platforms (RD treated with a combination of methotrexate, sulfasalazine at optimum tolerated doses with on-demand nonsteroidal anti-inflammatory agents and 30 healthy age-matched controls. Repeat measurement was done at 3 months in 60 patients. Results: Median MRP 8/14 levels in AxSpA patients was 3.00 (3.96) μg/ml compared to 2.3 (3.29) μg/ml in controls (P = 0.2). Median baseline MRP 8/14 levels in ASAS 20 responders at 6 months (n = 36) was 3.6 (4.1) μg/ml compared to 2.4 (4.8) μg/ml in nonresponders (n = 35) (P = 0.4). Median △ (baseline to 3 months) MRP 8/14 levels in ASAS 20 responders at 6 months (n = 33) was – 1 (−2.7) μg/ml compared to − 0.2 (−3.8) μg/ml for nonresponders (n = 27) (P = 0.5). Among the 83 patients with 138 disease activity assessments at baseline and 3 months post therapy, median MRP 8/14 in active disease (bath ankylosing spondylitis disease activity index [BASDAI] ≥4) (n = 112) was 2.2 (3.8) μg/ml, compared to 2 (2.3) μg/ml (P = 0.5) in inactive disease (BASDAI Conclusion: Serum MRP 8/14 did not serve as a theragnostic biomarker in our cohort of AxSpA patients treated with combination DMARDs and on-demand NSAIDs.

Disease activity trajectories in early rheumatoid arthritis following intensive DMARD therapy over 3 years: association with persistence to therapy.

To identify the disease activity trajectories during intensive triple disease modifying anti-rheumatic drug (DMARD) therapy over 3 years in rheumatoid arthritis (RA) patients and to evaluate the association with treatment persistence. Disease Activity Score in 28 joints, baseline risk factors and medication usage were obtained from a longitudinal observational cohort of early RA patients, most of whom were treated with combination DMARD therapy consisting of methotrexate, sulfasalazine and hydroxychloroquine. Persistence of each DMARD was defined as the duration of time from initiation to cessation. A group-based trajectory modelling technique was used to identify disease activity trajectories. Three disease activity trajectories (good [43.8%], moderate [39.7%] and poor [16.5%]) were identified in a cohort of 297 patients. Most baseline risk factors, medication usage, the rate of treatment persistence and the effect of persistence on disease activity differed among patients in each of the three trajectories. Although the rate of persistence was higher in the trajectory with a good outcome, the association with persistence was more pronounced among patients who were in the poor outcome trajectory. Persistence with at least two or all three baseline DMARDs was associated with a decrease in disease activity to a broadly similar degree in all trajectories. After correction for other baseline prognostic factors, persistence with initial DMARDs contributes to heterogeneity in disease activity trajectory and there was an association between persistence with initial DMARD therapy and lower long-term disease activity.

Active Foot Synovitis in Patients With Rheumatoid Arthritis: Unstable Remission Status, Radiographic Progression, and Worse Functional Outcomes in Patients With Foot Synovitis in Apparent Remission.

To determine whether foot synovitis is associated with adverse radiographic and functional outcomes after 3 years in an inception rheumatoid arthritis (RA) cohort receiving treat-to-target combination disease-modifying antirheumatic drug therapy. Disease activity was assessed in early RA patients (n = 266) using the Disease Activity Score in 28 joints, Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI). Radiographic outcomes were assessed with annual hand and feet radiographs and quality of life with the Short Form 36 (SF-36). The prevalence of remission and foot synovitis was calculated using marginal binomial generalized estimating equations, transition between remission and nonremission states by a multistate Markov model, and changes in radiographic scores by a negative binomial mixed regression log-link model. Population-matched SF-36 data were analyzed by mixed-effects linear regression. Disease activity scores that omit foot joints were modest in their ability to capture foot synovitis. Despite the relative stringency of the SDAI and CDAI for remission, 25-36% of patients in remission had foot synovitis. In patients in remission, foot synovitis predicted transition from remission into relapse by up to 2-fold. The sustainability of remission markedly influenced the progression of erosion scores (P = 0.006). After adjusting for disease activity, foot synovitis was associated with worse SF-36 physical functioning scores (P = 0.025). Disease activity measures that omit foot joints capture foot synovitis poorly. When it is used to define remission, foot synovitis is found in a substantial proportion of patients, which predicts relapse and worse physical function. Foot synovitis influences the sustainability of remission, which in turn markedly influences radiographic progression. Regardless of remission status, persistent foot synovitis should prompt therapy escalation in order to improve long-term outcomes.

Claims for disease-modifying therapy by Alberta non-insured health benefits clients.

BackgroundUncontrolled disease activity in inflammatory diseases of the joints, skin and bowel leads to morbidity and disability. Disease-modifying therapies are widely used to suppress this disease activity, but cost-coverage is variable. For Treaty First Nations and Inuit people in Canada without alternative private or public health insurance, cost-coverage for disease-modifying therapy is provided through Non-Insured Health Benefits (NIHB). Our objective was to describe the prevalence and patterns of treatment with disease-modifying therapy for the NIHB claimant population, and also examine adjuvant therapy (analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids) use.MethodsCases (n = 2512) were defined by ≥1 claim for a disease-modifying anti-rheumatic drug (DMARD) or biologic between 1999 and 2012 in the NIHB pharmacy claim database. The proportion of the population with claims for individual agents and drug classes annually was calculated to estimate annual incidence and prevalence rates for use of disease-modifying therapy, and the prevalence of use of individual DMARDs, biologics and adjuvants. Differences in the proportion accessing adjuvant therapies and median doses in the 6 months following initiation of disease-modifying therapies was estimated.ResultsThe incidence rate of treatment was calculated at an average of 127.5 cases per 100,000 population between 2001 and 2012, and the cumulative prevalence, accounting for patients lost to the database, increased and then stabilized at 1.3 % in the last three years of the study. Annual dispensation of methotrexate, combination DMARD therapy and biologic therapy approached 35 %, 19 %, and 10 % of the cohort respectively. A declining prevalence of claims for acetaminophen (28 % to 15 %) and anti-inflammatories (73 % to 63 %) occurred from 2000 to 2012, however corticosteroid (32 %) and opioid (65 %) dispensation remained stable. The proportion of patients with claims for NSAIDs (69.9 % to 61.1 %, p = 0.002), oral corticosteroids (45.4 % to 33.6 %, p < 0.001) and parenteral corticosteroids (16.2 % to 8.3 %, p = 0.002) decreased in the 6 months following biologic initiation.ConclusionsThe proportion of NIHB clients with active claims for disease-modifying therapy is lower than expected based on existing epidemiologic knowledge of the prevalence of inflammatory conditions in the First Nations and Inuit populations. These findings should be further explored in order to optimize treatment outcomes for NIHB claimants with inflammatory disease.

Efficacy of disease modifying anti-rheumatic drugs on bone destruction in rheumatoid arthritis

There had been proved the efficacy of preventing bone destruction by using disease modifying anti-rheumatic drugs (DMARDS) such as methotrexate(MTX). A certain combination of DMARDS is more effective than treated alone. But the data about DMARDS combination therapy or DMARDS used mainly in Japan is not abundant, and there needed to establish the evidences of them.

Predictors of treatment initiation with tumor necrosis factor-α inhibitors in patients with rheumatoid arthritis.

Introduction of biologic disease-modifying antirheumatic drugs (DMARDs) has revolutionized treatment in patients with rheumatoid arthritis (RA). However, due to substantially higher costs of biologics compared with nonbiologics, patients with less insurance generosity may have difficulty affording these agents, which may lead to potential access disparities. To identify factors affecting treatment initiation with tumor necrosis factor (TNF)-α inhibitor biologics in patients with RA. Health insurance claims data derived from Truven's MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits (2007-2010) were used to conduct a retrospective cohort study. Two separate cohorts of RA patients were identified: (1) monotherapy nonbiologic DMARD users and (2) combination therapy nonbiologic DMARD users. The primary outcome was TNF-α inhibitor initiation 12 months following an index inpatient or outpatient RA visit during 2008-2009. Predictors were measured 12 months pre-index and grouped into predisposing, enabling, or need factors based on Andersen's Behavior Model. Predisposing variables included age, sex, and geographic location; enabling variables included insurance-related factors such as capitation, payer type, and insurance generosity, which was defined using cost-sharing information from prescriptions filled by the patients in the previous year; and need variables included disease-related factors such as severity of RA, use of pain control medications, and presence of other comorbidities. Hierarchical logistic regression models were used to derive estimates of the impact of individual predictors. Initiation of TNF-α inhibitors was observed in 10.31% of the monotherapy nonbiologic DMARD users (1,922 of 18,641) and 13.09% of combination nonbiologic DMARD users (983 of 7,508). Among monotherapy nonbiologic DMARD users, initiation with TNF-α inhibitors was associated with the predisposing factors of age (OR = 0.98, 95% CI = 0.97-0.98 for each year increase) and geographic region (Midwest vs. South OR = 0.83, 95% CI = 0.73-0.93; Northeast vs. South OR = 0.77, 95% CI = 0.64-0.92; and West vs. South OR = 0.86, 95% CI = 0.74-0.99); enabling factors of visit to rheumatologists (1 visit vs. no visit OR = 1.22, 95% CI = 1.01-1.46), health insurance type (commercial vs. Medicare supplemental OR = 0.79, 95% CI = 0.66-0.95), and drug benefit generosity (above average vs. poor OR = 1.16, 95% CI = 1.01-1.34 and most generous vs. poor OR = 1.21, 95% CI = 1.05-1.40); and need factors of RA severity (OR = 1.19, 95% CI = 1.14-1.23 for each unit increase in a claims-based RA severity index [CIRAS]), pre-index pain reliever use (steroids OR = 1.81, 95% CI = 1.62-2.02; nonselective nonsteroidal anti-inflammatory drugs [NSAID] OR = 1.17, 95% CI = 1.05-1.31; COX-2 inhibitors OR = 1.22, 95% CI = 1.05-1.41), and comorbidities (OR = 0.94, 95% CI = 0.90-0.99 for each unit increase in a comorbidity index). Treatment initiation with TNF-α inhibitors among patients with combination therapy nonbiologic DMARDs use at baseline was associated with age (OR = 0.98, 95% CI = 0.97-0.99 for each year increase) and region (Midwest vs. South OR = 0.81, 95% CI = 0.68-0.96). Stronger associations with some of the need factors were observed (CIRAS OR = 1.28, 95% CI = 1.21-1.35 for each unit increase, steroids use OR = 2.05, 95% CI = 1.73-2.42, and nonselective NSAID use OR = 1.36, 95% CI = 1.17-1.58) in these patients compared with the monotherapy nonbiologic DMARD users. However, unlike the monotherapy DMARD user group, the enabling factors of health insurance type and drug benefit generosity were not found to be associated with TNF-α inhibitor initiation among nonbiologic DMARD combination therapy users. Potential disparities in the initiation of TNF-α inhibitors among RA patients on monotherapy DMARDs at baseline were noted among older patients, patients in certain geographic region of the United States, and patients with less generous prescription drug benefits. Although future research should examine the impact of these disparities on health outcomes, payers should be aware of the potential for undertreatment among these groups of RA patients when making formulary decisions.

Rheumatoid arthritis in the developing world: stepping up to the challenge

The ‘developing’ world is defined by low gross domestic product, level of education and life expectancy and includes countries in Sub-Saharan Africa, Central and South-East Asia, as well as parts of Central and South America. Financial and human resource constraints impact negatively on health outcomes of chronic diseases like rheumatoid arthritis (RA). A 46-year-old businesswoman in the Netherlands with RA is likely to have early intervention with disease-modifying antirheumatic drugs (DMARDs), resulting in disease remission or low disease activity within 6 months of symptom development [1]. In stark contrast, a 46-year-old domestic worker in peri-urban Soweto, South Africa, will probably experience late diagnosis of her RA and a delay in initiation of DMARD therapy often running into years [2]. Consequently, the South African patient is much more prone than her Dutch counterpart to develop significant functional disability and to be unemployed within 2 years of symptom onset. Moreover, the psychosocial consequences of physical disability from poorly controlled RA are likely to be more severe in this setting. Poor infrastructure leading to lack of electricity and hot water, having to carry water and use of outside toilets, inadequate public transport necessitating walking long distances, poor social support systems and social isolation may be some of her key experiences [3]. Low levels of formal education impact negatively on the risk of depression, possibilities of modifying employment to accommodate disabilities, and may mean that patients take a less active role in problem-solving [4]. Moreover, in resource-constrained countries, there is limited access to biologic treatment and joint replacement surgery. There is a large burden of infectious diseases, especially HIV infection and tuberculosis (TB), which not only overwhelm health services but also present diagnostic and therapeutic challenges in patients with inflammatory arthritis. HIVassociated arthritis can masquerade as RA, and corticosteroids and anti-TNF biologics need to be used with caution because of the high risk of TB reactivation. Given the myriad of challenges in optimising RA management, what should the priorities be? A survey in Latin American and Caribbean countries identifies a number of strategies to improve care of RA patients [5]. In our view, the most important intervention is training of health care professionals, including family practitioners, primary care nurses, occupational and physiotherapists and orthopaedic surgeons, to recognise early inflammatory arthritis and make appropriate referrals to specialist centres. The next priority would be for rheumatology specialist centres to fast track patients with possible inflammatory arthritis and initiate DMARDs promptly. Methotrexate (MTX) is relatively inexpensive and readily available in most parts of the world and is used optimally if given early and escalated as part of a tight control strategy [6].When used as monotherapy, MTX induces low disease activity in 20–40 % of patients [7, 8], failing of which, combination DMARD therapy can be used to control disease activity. Using this strategy, only a minority of patients will have an inadequate response to traditional DMARDs and will require biologic DMARDs to control disease activity. For these patients, rheumatology groups need to lobby funders and healthcare authorities to B. Hodkinson (*) Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa e-mail: drbridget@gmail.com

Addition of another disease-modifying anti-rheumatic drug to methotrexate reduces the flare rate within 2 years after infliximab discontinuation in patients with rheumatoid arthritis: An open, randomized, controlled trial

Objectives. We examined whether the addition of another conventional disease-modifying anti-rheumatic drugs (DMARDs) to methotrexate (MTX) upon infliximab (IFX) discontinuation in well-controlled rheumatoid arthritis (RA) patients could suppress subsequent disease flare.Methods. RA patients maintaining DAS28-CRP (Disease Activity Score of 28 joints with C-reactive protein) scores < 2.6 for ≥ 6 months with IFX were randomized either to receive addition of bucillamine (BUC) to MTX (BUC + MTX group; n = 24) or not (MTX group; n = 31) upon discontinuing IFX. The primary endpoint was the flare rate within 2 years of IFX discontinuation.Results. Six patients discontinuing MTX during the study were excluded from analyses. Seventeen patients (63.0%) experienced flares in the MTX group, which was significantly reduced in the BUC + MTX group (31.8%; p = 0.045). Further, the flare rates differed significantly between remission and non-remission by a Boolean definition upon IFX discontinuation in the MTX group (40.0% vs. 91.7%, respectively; p = 0.014), but they were comparable in the BUC + MTX group. BUC treatment was interrupted in seven patients due to rash, proteinuria and incompliance.Conclusions. DMARDs combination therapy may be a better treatment strategy than MTX monotherapy for maintaining RA control after successful discontinuation of biological agents.

SAT0026 Targeted Treatment and Combination Dmard Therapy are Additively Important for Reaching Remission in Early Rheumatoid Arthritis

BackgroundMultiple trials have shown that in early rheumatoid arthritis (RA), both monitoring disease activity and aiming at remission, as well as using combinations of disease modifying antirheumatic drugs (DMARDs) are...

THU0244 Drug Therapy in Undifferentiated Arthritis: A Systematic Literature Review

BackgroundPart of the cases with undifferentiated arthritis (UA), an inflammatory oligo-arthritis without definitive diagnosis, may be a first manifestation of rheumatoid arthritis (RA). As early treatment in RA results in...

THU0144 Two Year Radiological Follow-Up of Early Rheumatoid Arthritis Patients Treated with Initial Step Up Monotherapy or Initial Step Down Therapy with Glucocorticoids, Followed by a Tight Control Approach

BackgroundCombination therapy with disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids(GCs) or biological agents is superior in achieving clinical response and preventing joint damage compared to DMARD monotherapy in patients with early...

A two-step treatment strategy trial in patients with early arthritis aimed at achieving remission: the IMPROVED study

ObjectivesTo assess which treatment strategy is most effective in inducing remission in early (rheumatoid) arthritis.Methods610 patients with early rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) started treatment with...

Conventional disease‐modifying antirheumatic drugs to treat rheumatoid arthritis

AbstractRheumatoid arthritis (RA) is characterized by a symmetric polyarthritis of unknown etiology that, if untreated or unresponsive to therapy, typically leads to deformities and destruction of joints through the erosion of cartilage and bone. Currently available disease‐modifying antirheumatic drugs (DMARDs) can control synovitis and may slow, or even stop, radiographic progression, improve function and quality of life, and normalize mortality rates. This review gives a brief overview on commonly used conventional DMARDs and their role in the current management of RA. Methotrexate is still considered the gold standard among the DMARDs, and is widely accepted as first‐line treatment in the management of RA. Other DMARDs are less frequently used in monotherapy or as first‐line agents but continue to have a role as antirheumatic agents in select patients. DMARD combination therapy may still represent a valuable therapeutic option in patients who fail to DMARD monotherapy or in whom combination therapy is considered initially. This review will focus on a better understanding of the critical importance of early DMARD treatment, the goal of remission and the need for tight control and adaptive modification in case of inadequate response or intolerance. Drug Dev Res 72:657–663, 2011. © 2011 Wiley Periodicals, Inc.

Disease‐modifying anti‐rheumatic drug usage, prescribing patterns and disease activity in rheumatoid arthritis patients in community‐based practice

Our aim was to examine the spectrum of disease activity and usage of disease-modifying anti-rheumatic drugs (DMARD) in rheumatoid arthritis (RA) patients seen over a period of 12 months in community-based rheumatology practice. Data were prospectively collected on 1059 consecutive RA patients who attended two private, community-based rheumatology clinics from 1 May 2007 to 1 May 2008. Information on patient demographics, medication history and disease activity was collected. Life table graphs were developed to track medication retention over time. Statistical significance was determined by log-rank tests. One thousand and fifty-nine patients with RA were entered into the database over a 12-month period. Eight hundred and twenty-six patients (85%) were treated with single or combination conventional DMARD compared with 159 patients (15%) on a biologic DMARD either alone or in combination. Methotrexate monotherapy was the most commonly prescribed DMARD, used in 41% of patients studied. Almost half (47%) were on combination DMARD therapy. Methotrexate and tumour necrosis factor inhibitors had the highest retention rate over 12 and 30 months since first prescription. A large proportion of patients (47%) had moderate disease activity. Rates of biologic DMARD usage were similar to other studies and the predominance of methotrexate use was also in keeping with current recommendations for management of RA. There appears to be a significant unmet need for improved disease control among RA patients with moderate disease activity, which requires further investigation.