Disease-modifying Antirheumatic Drugs Regimens Research Articles

Application of T-cell receptor repertoire as a novel monitor in dynamic tracking and assessment: A cohort-study based on RA patients.

T-cell receptor repertoire (TCRR) sequencing has been widely applied in many fields as a novel tool. This study explored characteristics of TCRR in detail with a cohort of 598 rheumatoid arthritis (RA) patients before and after anti-rheumatic treatments. We highlighted the abnormal TCRR distribution in RA characterized by decreased diversity and increased proportion of hyperexpanded clones (HECs), which was potentially attributed to skewed usage of global V/J segments but not a few certain ones. Enriched motifs analysis in RA community demonstrated the huge heterogeneity of CDR3 sequences, so that individual factors are strongly recommended to be taken into consideration when it comes to clinical application of TCRR. Disease-modifying antirheumatic drugs (DMARDs) can regulate immune system through recovery of TCRR richness to relieve symptoms. Remarkably, sensitive gene profile and advantageous gene profile were identified in this study as new biomarkers for different DMARDs regimens.

Risk for Serious Infection With Low-Dose Glucocorticoids in Patients With Rheumatoid Arthritis : A Cohort Study.

Low-dose glucocorticoids are frequently used for the management of rheumatoid arthritis (RA) and other chronic conditions, but the safety of long-term use remains uncertain. To quantify the risk for hospitalized infection with long-term use of low-dose glucocorticoids in patients with RA receiving stable disease-modifying antirheumatic drug (DMARD) therapy. Retrospective cohort study. Medicare claims data and Optum's deidentified Clinformatics Data Mart database from 2006 to 2015. Adults with RA receiving a stable DMARD regimen for more than 6 months. Associations between glucocorticoid dose (none, ≤5 mg/d, >5 to 10 mg/d, and >10 mg/d) and hospitalized infection were evaluated using inverse probability-weighted analyses, with 1-year cumulative incidence predicted from weighted models. 247297 observations were identified among 172041 patients in Medicare and 58279 observations among 44118 patients in Optum. After 6 months of stable DMARD use, 47.1% of Medicare patients and 39.5% of Optum patients were receiving glucocorticoids. The 1-year cumulative incidence of hospitalized infection in Medicare patients not receiving glucocorticoids was 8.6% versus 11.0% (95% CI, 10.6% to 11.5%) for glucocorticoid dose of 5 mg or less per day, 14.4% (CI, 13.8% to 15.1%) for greater than 5 to 10 mg/d, and 17.7% (CI, 16.5% to 19.1%) for greater than 10 mg/d (all P < 0.001 vs. no glucocorticoids). The 1-year cumulative incidence of hospitalized infection in Optum patients not receiving glucocorticoids was 4.0% versus 5.2% (CI, 4.7% to 5.8%) for glucocorticoid dose of 5 mg or less per day, 8.1% (CI, 7.0% to 9.3%) for greater than 5 to 10 mg/d, and 10.6% (CI, 8.5% to 13.2%) for greater than 10 mg/d (all P < 0.001 vs. no glucocorticoids). Potential for residual confounding and misclassification of glucocorticoid dose. In patients with RA receiving stable DMARD therapy, glucocorticoids were associated with a dose-dependent increase in the risk for serious infection, with small but significant risks even at doses of 5 mg or less per day. Clinicians should balance the benefits of low-dose glucocorticoids with this potential risk. National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Rate and causes of noncompliance with disease-modifying antirheumatic drug regimens in patients with rheumatoid arthritis.

To determine the prevalence and factors associated with medication noncompliance by Thai patients with rheumatoid arthritis (RA). This prospective cohort study enrolled 443 adult RA patients (≥ 18years) who were followed up at the outpatient rheumatology clinics of Siriraj Hospital and Phramongkutklao Hospital between May 2018 and December 2019. Medication noncompliance was assessed using the Compliance Questionnaire for Rheumatology-19 (CQR-19). A score of 0 indicated complete noncompliance, whereas a score of 100 indicated a perfect compliance. An unsatisfactory compliance was arbitrarily defined as a taking compliance of ≤ 80%. The prevalence of medication noncompliance was 22.1%. The most common cause was forgetting to take medications due to a busy work schedule. In a univariate analysis, the factors that were significantly related to medication noncompliance were age, income, number of comorbidities, functional status as measured by the Health Assessment Questionnaire (HAQ), number of prescribed pills per day, and number of types of prescribed medications per day. In a subsequent backward stepwise multiple logistic regression analysis, only 2 factors were found to be negatively associated with medication noncompliance: age (risk ratio, 0.98; 95% CI, 0.96-0.99; p, 0.048) and HAQ (risk ratio, 0.62; 95% CI, 0.39-0.98; p, 0.041). Medication noncompliance is common in patients with RA. As this may lead to unfavorable outcomes, patient education related to drug compliance should be addressed and emphasized in daily practice. Key Points • Medication noncompliance is common in patients with RA. • Forgetting to take pills was the most frequent explanation offered for noncompliance. • All patients should be strongly encouraged to comply with the recommended drug regimens.

Pharmacotherapeutic considerations for systemic rheumatic diseases amid the COVID-19 pandemic: more questions than answers.

Thus far, associations between the presence of systemic rheumatic disease and an increased risk of novel coronavirus disease 2019 (COVID-19) acquisition or a worse prognosis from COVID-19 have not been conclusive. It is not known for certain if there is an association between any pharmacological agent used for rheumatologic treatment, including biological and non-biological disease-modifying antirheumatic drugs (DMARDs), and an increased risk of COVID-19 acquisition or adverse outcomes from COVID-19, although these agents have been associated with an overall higher risk of infections. The pharmacological management of patients with a rheumatic disease without COVID-19 should currently follow usual treatment approaches. Individualized approaches to adjusting DMARD regimens in patients with documented COVID-19 seems prudent, with specific attention paid to the severity of the infection. Patients receiving antimalarials (hydroxychloroquine/chloroquine) may continue treatment with these agents. Treatment with sulfasalazine, methotrexate, leflunomide, immunosuppressants and biological agents other than interluekin-6 receptor inhibitors and JAK inhibitors should be stopped or withheld. It should be reasonable to resume DMARD treatment when patients are no longer symptomatic and at least 2 weeks after documentation of COVID-19, although the decision should be individualized, preferably based on infection severity.

Cardiovascular Disease Risk in Older Adults and Elderly Patients with Rheumatoid Arthritis: What Role Can Disease-Modifying Antirheumatic Drugs Play in Cardiovascular Risk Reduction?

The prevalence of rheumatoid arthritis (RA), the most common autoimmune inflammatory arthritis, is increasing, partly due to the aging of the general population. RA is an independent risk factor for the development of cardiovascular disease (CVD). Older adults and elderly patients with RA develop CVD at a younger age compared with their general population peers. Both the traditional cardiovascular risk factors (age, sex, smoking, diabetes mellitus, hypertension), and systemic inflammation (i.e. high disease activity) are contributors to accelerated CVD in people with RA. Of the disease-modifying antirheumatic drugs (DMARDs) used for RA treatment, methotrexate, triple combination oral therapy (methotrexate, sulfasalazine, and hydroxychloroquine), tumor necrosis factor inhibitor biologicals, and abatacept have the strongest data in favor of the reduction of cardiovascular events in patients with RA. A treat-to-target strategy should be employed in older adults and elderly patients with RA to ensure appropriate reduction in cardiovascular risk, which can also prevent short- and long-term musculoskeletal disability. Our review findings are in line with the 2016 European League Against Rheumatism guideline recommendations, specifically: (1) RA disease activity should be controlled with an optimal DMARD regimen using a treat-to-target approach; (2) the lipid profile should be assessed and monitored in every older adult and elderly RA patient; (3) CVD risk factors, including smoking cessation, blood pressure, and blood glucose control, should be optimized; (4) RA treatment should be initiated as soon as possible; and (5) shared decision making regarding the treatment of patients with RA should include a discussion on the potential amelioration of increased cardiovascular risk.

Patterns of Systemic Treatment for Psoriatic Arthritis in the US: 2004-2015.

To examine trends in the use of systemic disease-modifying antirheumatic drugs (DMARDs) among patients with psoriatic arthritis (PsA) in the US. Using claims data (2004-2015) from a large US commercial health plan, we identified patients with PsA who initiated DMARD therapy. We examined baseline patient characteristics and initial treatment patterns. We then assessed changes in the DMARD regimen over the 12-month period after the first DMARD initiation date. Using Poisson regression, we estimated age- and sex-adjusted incidence rates of treatment changes in each calendar year. We identified 9,222 PsA patients who initiated DMARD therapy (42.8% biologic DMARDs [bDMARDs] and 57.2% conventional synthetic DMARDs [csDMARDs]). Initiators of bDMARDs were younger than those initiating csDMARDs (mean ± SD age 48 ± 13 versus 52 ± 14 years) and generally had fewer comorbidities, but a higher proportion of bDMARD initiators received nonsystemic treatments for psoriasis at baseline. Methotrexate was the most frequently used DMARD, constituting 80.6% of csDMARD initiations. Etanercept (49.1%) was the most commonly prescribed bDMARD, followed by adalimumab (34.4%). During the 12-month followup after the first DMARD initiation, 20.1% of bDMARD initiators and 31.1% of csDMARD initiators had their initial DMARD regimen modified, with an increasing trend in treatment modifications over the 11-year study period (P = 0.03). Overall, 5.3% of patients discontinued treatment, but the rates of discontinuation decreased over time (P < 0.001). In this large cohort of PsA patients with DMARD initiation, more than 40% were treated with a bDMARD. We found an increasing trend in treatment modification after use of the initial DMARD and a decreasing trend in complete DMARD discontinuation over the past decade.

Does Regular Use of a Complementary Medicine of Olea Europe and Ficus carica Have Adverse Effects on Lipid Profile and Fasting Blood Glucose of Rheumatoid Arthritis (RA) Patients Under Treatment with DMARD Regimens Containing Methotrexate?

Rheumatoid arthritis (RA) patients are vulnerable to cardiovascular morbidity and mortality in which atherosclerosis plays a major role. In this study, the lipid profile and fasting blood sugar (FBS) of RA patients receiving a complementary medicine of olive and fig, as add-on therapy for routine disease-modifying antirheumatic drugs (DMARDs) regimen containing low dose methotrexate (MTX), were studied. A randomized controlled clinical trial was designed. Adult RA patients were randomly allocated in two groups receiving routine DMARDs regimen (control group) and routine DMARDs regimen plus the herbal supplementary formulation of olive oil, fig and olive fruits (intervention group). Patients were followed every 4 weeks for total study period of 16 weeks. In addition to demographic and medical history of the patients, the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), the atherogenic index of plasma (AIP) defined as log(TG/HDL-C), and the fasting blood sugar (FBS) were determined and recorded. 56 patients (control = 27 and intervention = 29), with mean ± sd age of 50.9 ± 12.3 years completed the study. Average MTX dose received by intervention and control groups were 24.30 ± 18.39 and 17.61 ± 15.53 mg/week, respectively (p = 0.11). Repeated measures analysis of variance (ANOVA) revealed that differences between lipid profile indicators and FBS in the two study groups were not statistically significant (P>0.05). No additional substantial adverse reaction was seen in the study groups. Our findings are more reassuring for patients and their doctors to trust on the safety of the investigated complementary preparation to be used as add-on therapy to manage rheumatoid arthritis.

Study of the Effect of an Oral Formulation of Fig and Olive on Rheumatoid Arthritis (RA) Remission Indicators: A Randomized Clinical Trial.

This study was designed to explore the complementary effects of a combination formulation of olive oil, olive and fig fruits on RA remission indicators. A randomized controlled clinical trial was designed. Adult RA patients were randomly divided into two groups receiving routine Disease-modifying antirheumatic drugs (DMARDs) regimen (control group) and routine DMARDs regimen plus the herbal supplementary formulation of olive oil, fig and olive fruits (intervention group). Patients were followed every 4 weeks for total study period of 16 weeks. In addition to demographic and medical history of the patients, the Disease Activity Score with 28-joint counts based on Erythrocyte Sedimentation Rate (DAS28_ESR) were recorded. SPSS (version 22.0) software was used to analyze data, assuming p<0.05 as significance level. 56 patients (control = 27 and intervention = 29), with mean ± sd age of 50.91 ± 12.26 years completed the study. Repeated measures analysis revealed that differences between remission indicators in the two study groups were not statistically significant, however, there was a p = 0.03 for the within-subjects contrast test of the Patient Global Assessment (PtGA), approving a nonlinear change for PtGA with respect to time. No between groups differences in adjunct drug therapy pattern for disease flares were seen. In conclusion, although, non-significant changes in the study variable of DAS28_ESR is in agreement with few previous reports, nevertheless, trends in its reduction in the intervention group along with the significant delayed PtGA score improvements occurred in the intervention group convince us to suggest further investigations on the supplementary olive and fig products, with a longer follow up periods.

Pharmacogenomics of NAT2 and ABCG2 influence the toxicity and efficacy of sulphasalazine containing DMARD regimens in early rheumatoid arthritis

Sulphasalazine (SSA) is a disease modifying anti-rheumatic drug (DMARD) that is commonly used to treat rheumatoid arthritis (RA). Plasma levels of SSA and its metabolite sulphapyridine are influenced by common polymorphisms in genes that encode N-acetyl transferase 2 (NAT2) and ATP-binding cassette protein G2 (ABCG2). Study participants had early RA that was treated with a combination DMARD regimen that included SSA. Toxicity was defined by cessation of SSA due to adverse effects and response as remission after 12 months of treatment. The effect of variables on toxicity was assessed by a Cox-proportional Hazard model and response by logistic regression. After correction for conventional variables, toxicity in 229 participants was influenced by NAT2 phenotype (hazard ratio=1.74 (95% confidence interval (CI) 1.01-3.21), P=0.044) and remission in 141 participants was associated with ABCG2 genotype (odds ratio=3.34 (95% CI 1.18-9.50), P=0.024). In our sample of early RA patients who were primarily treated with a combination of DMARDs, common variants in genes that encode NAT2 and ABCG2 were associated respectively with toxicity and response to SSA.

SAT0556 Predictors of Intensive Anti-Rheumatic Therapy in Early Care for Rheumatoid Arthritis

BackgroundEarly, intensive disease-modifying anti-rheumatic drug (DMARD) therapy is an effective strategy to limit disease progression in rheumatoid arthritis (RA). It was recently reported that DMARD therapy is initiated in advance...

Patient satisfaction with nursing consultations in a rheumatology outpatient clinic: a 21-month randomised controlled trial in patients with inflammatory arthritides

ObjectiveTo study the effect of individual nursing consultations in patients treated with disease-modifying antirheumatic drugs (DMARDs) in a rheumatology outpatient setting.MethodsPatients with inflammatory arthritides (IA) who had started with a...

Patients’ views about treatment with combination therapy for Rheumatoid Arthritis: a comparative qualitative study

BackgroundCombinations of disease-modifying anti-rheumatic drugs (DMARDs) are increasingly used to control active rheumatoid arthritis (RA); however there is little information about patients’ perspectives, their expectations, concerns and experiences of this intensive treatment.MethodWe interviewed a quota sample of 18 patients from a single tertiary outpatient clinic, stratified by gender, ethnicity and age, based on the outpatient clinic population. Patients with early RA (<2 years) received combined conventional DMARDs; patients with established RA (>2 years) received combined conventional DMARDs or DMARDs with biologics.ResultsFour main themes emerged from the analytical framework: (i) patients’ expectations about the combined treatment focuses mainly on physical symptoms; (ii) the impact of the treatment on quality of life varied with the new medication in both groups (iii) concerns about new interventions concentrated mainly on potential side effects; and (iv) combination therapy can be self-managed in close collaboration with clinic staff, but this requires individualised management approaches. These themes resonate with von Korff’s collaborative management of chronic illness model.ConclusionTo our knowledge this is the first qualitative study that examined systematically in patients with early and established RA their expectations, impact on quality of life, concerns about side effects and the management of the treatment when taking combined medication with DMARDs or DMARDs and biologics. Patients have generally positive views of combination DMARDs. Within routine practice settings, achieving medication concordance with complex combined DMARD regimens is challenging, and the concerns vary between patients; careful individual assessments are essential to successfully deliver such intensive treatment.

Changes in cotherapies after initiation of disease‐modifying antirheumatic drug therapy in patients with rheumatoid arthritis

Objective. We hypothesized that initiation of a new disease-modifying antirheumatic drug (DMARD) for treatment of rheumatoid arthritis (RA) would decrease the use of corticosteroids, nonsteroidal antiinflammatory drugs (NSAIDs), and narcotics.Methods. Using administrative databases, we assembled 4 retrospective cohorts of RA patients (1998-2005) and identified 5 groups initiating DMARD regimens: methotrexate (MTX) with (new MTX) or without (first MTX) use of other nonbiologic DMARDs in the previous year; new hydroxychloroquine (HCQ) and/or sulfasalazine (SSZ; new HCQ/SSZ)and new leflunomide (new LEF), both with previous use of MTX; and new tumor necrosis factor α (TNFα) antagonists(new anti-TNF). We compared within-person differences in any use of cotherapies (≥ prescription) between the 6 months before and the 6-12 months after DMARD initiation.Results. Among 32,476 DMARD initiators, the prevalence of corticosteroid, NSAID, and narcotic use increased by 15%, 5%,and 6%, respectively, in the 6 months before initiation compared to the previous 6 months, suggesting worsening of the disease. In the 6-12 months after initiation for most initiator groups, more patients stopped using corticosteroids and NSAIDs than started, with overall decreases of 8.9% (95% confidence interval [95% CI] 8.4-9.4%) for corticosteroids and 12.9% (95%CI 12.3-13.4%) for NSAIDs. The proportion of narcotic users changed little (overall decrease of 2.5%; 95% CI 1.9-3.0%).Conclusion. Use of all 3 cotherapies increased in the 6 months before initiation of new DMARD regimens for RA. Use of corticosteroids and NSAIDs decreased modestly 6-12 months after initiation, but there was only a very small decrease in narcotic use. These differential changes require further study.

Association Between Disease-Modifying Antirheumatic Drugs and Diabetes Risk in Patients With Rheumatoid Arthritis and Psoriasis

Rheumatoid arthritis (RA) and psoriasis have been linked with insulin resistance and diabetes mellitus (DM). Prior investigations suggest that systemic immunosuppressive drugs may improve insulin resistance and reduce the risk of DM. To compare the risk of newly recorded DM among participants diagnosed with RA or psoriasis based on use of a variety of disease-modifying antirheumatic drugs (DMARDs). A retrospective cohort study among 121,280 patients with a diagnosis of either RA or psoriasis on at least 2 visits. The analyses were conducted in the context of 2 large health insurance programs, 1 in Canada and 1 in the United States, using administrative data. The mean follow-up was 5.8 months and began with the first prescription for a DMARD after study eligibility was met. Drug regimens were categorized into 4 mutually exclusive groups: (1) tumor necrosis factor (TNF) inhibitors with or without other DMARDs; (2) methotrexate without TNF inhibitors or hydroxychloroquine; (3) hydroxychloroquine without TNF inhibitors or methotrexate; or (4) other nonbiologic DMARDs without TNF inhibitors, methotrexate, or hydroxychloroquine (reference exposure). Newly recorded DM as evidenced by a new diagnosis of DM with use of a DM-specific medication. The study cohort consisted of 13,905 participants with 22,493 treatment episodes starting 1 of the categories of DMARD regimens between January 1996 and June 2008. New diabetes cases and respective incidence rates per 1000 person-years were: other nonbiologic DMARDs (55 cases among 3993 treatment episodes; rate, 50.2; 95% confidence interval [CI], 47.3-53.2); TNF inhibitors (80 cases among 4623 treatment episodes; rate, 19.7; 95% CI, 19.1-20.3); methotrexate (82 cases among 8195 treatment episodes; rate, 23.8; 95% CI, 23.0-24.6); and hydroxychloroquine (50 cases among 5682 treatment episodes; rate, 22.2; 95% CI, 21.3-23.1). The multivariate adjusted hazard ratios for DM were 0.62 (95% CI, 0.42-0.91) for TNF inhibitors, 0.77 (95% CI, 0.53-1.13) for methotrexate, and 0.54 (95% CI, 0.36-0.80) for hydroxychloroquine compared with other nonbiologic DMARDS. Among patients with RA or psoriasis, the adjusted risk of DM was lower for individuals starting a TNF inhibitor or hydroxychloroquine compared with initiation of other nonbiologic DMARDs.

Endothelial dysfunction in ankylosing spondylitis improves after tumor necrosis factor-α blockade

Chronic inflammation in ankylosing spondylitis (AS) is associated with vascular endothelial dysfunction. Infliximab improves inflammatory disease activity in AS patients, but its effect on endothelial dysfunction has still not been tested in these patients. Twelve anti-TNF naive AS patients (mean age, 32.6 +/- 3.94 years; disease duration, 5.6 +/- 0.8 years) with high disease activity [Bath ankylosing spondylitis disease activity index (BASDAI score > 4)] despite treatment with stable doses of conventional disease modifying anti-rheumatic drugs (DMARDs) were investigated. Inflammatory disease activity [BASDAI and Bath ankylosing spondylitis functional index (BASFI) scores, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels], serum nitrite concentration, and endothelium-dependent and endothelium-independent vasodilation of the brachial artery were measured at baseline and 12 weeks of therapy after single intravenous infusion of infliximab (5 mg/kg). Previous DMARD(s) regimen remained unchanged throughout the study period. After treatment with infliximab, flow-mediated vasodilation improved from 9.81 +/- 1.70% to 26.93 +/- 2.34% (p < 0.001), whereas there was no significant change in endothelium-independent vasodilation with nitroglycerin and baseline diameter (13.65 +/- 2.10% versus 14.59 +/- 1.93%, p = 0.08, and 4.45 +/- 0.15 versus 4.46 +/- 0.15 mm, p = 0.3, respectively). Nitrite concentration reduced from 6.50 +/- 0.21 to 2.57 +/- 0.18 micromol/l (p < 0.001), ESR from 40.90 +/- 6.00 to 11.50 +/- 1.38 mm in the first hour (p < 0.001), and CRP level from 29.08 +/- 4.11 to 2.69 +/- 0.43 mg/dl (p < 0.001). BASDAI and BASFI scores were significantly reduced from 5.40 +/- 1.14 to 1.40 +/- 0.70 (p < 0.05) and 5.05 +/- 1.76 to 0.20 +/- 0.63 (p < 0.05), respectively. The study suggests that in ankylosing spondylitis, endothelial dysfunction is a part of the disease process and infliximab improves both endothelial dysfunction and inflammatory disease activity.

Cost-Effectiveness of Sequential Therapy with Tumor Necrosis Factor Antagonists in Early Rheumatoid Arthritis

To estimate the comparative lifetime cost-effectiveness of sequenced therapy with tumor necrosis factor (TNF) antagonists as the initial therapeutic intervention for patients with early rheumatoid arthritis (RA). Because patients with RA switch regimens many times throughout the course of disease, sequenced therapeutic interventions were modeled, continuing until the last effective agent failed or death occurred. The model used published clinical outcomes from short-term, randomized controlled trials. Direct treatment costs and costs of lost productivity were modeled for each of 5 alternative treatment sequences. Incremental cost-effectiveness ratios are expressed as quality-adjusted lifeyears (QALY) gained. Treatment sequences that included TNF antagonists produced a greater number of QALY than conventional disease modifying antirheumatic drug regimens alone. The cost-effectiveness of sequenced therapy initiated with adalimumab plus methotrexate (MTX) extendedly dominated both infliximab-plus-MTX-initiated and etanercept sequences. The cost of adalimumab plus MTX per QALY was US $47,157 excluding productivity losses, and $19,663 including productivity losses. A supplementary sequence that incorporated adalimumab-plus-MTX-initiated first-line therapy followed by another TNF antagonist as second-line therapy was modeled; this sequence resulted in additional QALY gained and extendedly dominated all single-TNF strategies. Of the 3 single-TNF antagonist sequences, the adalimumab-plus-MTX-initiated sequence was cost-effective in producing the greatest number of QALY. Multiple TNF strategies, such as the supplementary sequence modeled in this analysis, may be cost-effective in producing even greater health gain.

Early rheumatoid arthritis: clinical and therapeutic evaluation in a tertiary care centre in India

Background Patients with early rheumatoid arthritis may show a qualitative change in their short-term outcome if they are treated at presentation. We tried to evaluate these patients on disease modifying antirheumatic drugs (DMARDs) commenced at diagnosis. Methods 110 consecutive patients enrolled in this study from our rheumatology clinic, fulfilling American College of Rheumatology (ACR) 1987 revised criteria for classification of RA with disease duration of less than 6 months who had not received any DMARD. Patients were randomized to two groups irrespective of clinical, serological and radiological findings and assigned to treatment with either MTX + HCQ or SSZ + HCQ and were followed for 6 months. Results There were statistically significant differences in clinical and laboratory parameters after 6 months in comparison to baseline within each group but not between the two groups. There was good correlation between DAS28 and CRP when compared at baseline and after 6 months of treatment in both the treatment groups. Conclusions Disease control is the real goal of treatment of early RA irrespective of the DMARD regimen employed. Radiological changes may be found even in early RA and may call for more aggressive management in some patients. Costly estimation of CRP should give way to simple estimation of DAS28.

Assessment of Adherence to and Persistence on Disease-Modifying Antirheumatic Drugs (DMARDs) in Patients With Rheumatoid Arthritis

Biologic disease-modifying antirheumatic drugs (DMARDs) are efficacious for treating rheumatoid arthritis (RA). However, measurements of relative effectiveness, including treatment adherence and persistence, are lacking. We evaluated adherence and persistence during new episodes of use of traditional and biologic DMARDs. Using Tennessee Medicaid databases (1995-2004), we assembled a retrospective cohort of patients diagnosed with RA, and identified new episodes of use for 12 DMARD regimens. We evaluated persistence through survival analyses, and adherence within episodes through the medication possession ratio. A risk score was included in the analyses to account for measured confounders. We identified 14,932 patients with RA; 6018 patients had 10,547 episodes of new use of DMARDs. Considering methotrexate as the reference and after adjustment for measured confounders, episodes of new use of sulfasalazine [adjusted hazard ratio (aHR) = 1.59; 95% confidence interval (CI) = 1.47-1.72] and infliximab alone (aHR = 1.37, 95% CI = 1.09-1.73) were more likely to be discontinued; and new episodes of etanercept (aHR = 0.82, 95% CI = 0.73-0.92) and methotrexate + adalimumab (aHR = 0.63, 95% CI = 0.48-0.84) were less likely to be discontinued. Compared with methotrexate, adherence was higher for leflunomide, infliximab, etanercept, and adalimumab and lower for sulfasalazine and all combined therapies. We developed an approach to assess persistence on and adherence to the most common DMARD therapies. In this large cohort, persistence and adherence to leflunomide and most biologic DMARD therapies were at least comparable to methotrexate. Adherence was lower for sulfasalazine and all combined therapies.

Real-world effectiveness of select biologic and DMARD monotherapy and combination therapy in the treatment of rheumatoid arthritis: results from the RADIUS observational registry

ABSTRACTObjective: To evaluate the effectiveness of select biologics, methotrexate (MTX), and other disease-modifying anti-rheumatic drugs (DMARDs) in the management of adult rheumatoid arthritis (RA) in routine clinical practice.Research design and methods: RADIUS (Rheumatoid Arthritis DMARD Intervention and Utilization Study) comprises two prospective, 5‐year, observational registries of over 10 000 patients. Over 4600 patients who initiated MTX or a biologic regimen (etanercept [ETN], infliximab [INF], ETN + MTX, and INF + MTX) and who had at least one on-regimen, follow-up evaluation, were included in this analysis. Adalimumab was not included because it had not yet received FDA approval at RADIUS initiation. Other common DMARD regimens ( N = 762) were also compared with MTX. Patients who initiated less commonly used regimens, such as anakinra or cyclosporine, and those who did not have at least one on-regimen, follow-up evaluation, were not eligible for this analysis. Because ESR/CRP measurements were often not available, a modified ACR20 response (mACR20), defined as three out of four response criteria excluding ESR/CRP, was used to assess response at 12 months. Logistic regression analysis was performed to control for baseline covariates that may affect outcomes.Main outcome measures: The primary endpoint was the proportion of patients who achieved a mACR20 response at 12 months post-RADIUS entry.Results: After adjusting for baseline covariates, patients receiving either ETN + MTX or ETN monotherapy were more likely to achieve a mACR20 response at 12 months than patients receiving MTX alone (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.09–1.52; p < 0.01 and OR 1.23, 95% CI 1.02–1.47; p < 0.05, respectively). Conversely, patients treated with MTX + leflunomide (LEF) were less likely to achieve a mACR20 response than those receiving MTX alone (OR 0.68, 95% CI 0.48–0.96; p < 0.05). Significant differences were not observed between patients receiving MTX alone and either INF + MTX, MTX + hydroxychloroquine, MTX + hydroxychloroquine + sulfasalazine, INF monotherapy, or LEF monotherapy.Conclusion: These data from routine rheumatology clinical practice settings highlight the effectiveness of common biologic and DMARD therapies, and provide additional data beyond those of randomized, controlled trials.

Current and future management approaches for rheumatoid arthritis

With the introduction of new disease-modifying antirheumatic drugs (DMARDs) and other therapeutic agents, the management of rheumatoid arthritis (RA) has shifted toward earlier, more aggressive therapy. The ultimate goal is to prevent structural joint damage that leads to pain and functional disability. Early diagnosis of RA is therefore essential, and early DMARD treatment combined with nonsteroidal anti-inflammatory drugs is recommended. Combination DMARD regimens and new biologic agents (anti-tumor necrosis factor [TNF] therapies [infliximab, etanercept] and the interleukin [IL]-1 antagonist [anakinra]) have emerged as viable options for early treatment of RA patients. These new biologic agents and future nonbiologic agents that target proteins in signaling cascades are likely to change the landscape of RA treatments.