DMARD Therapy Research Articles

OP0177 Randomized Comparison of Triple Dmard Therapy with Methotrexate Mono-Therapy

BackgroundEULAR/ACR guidelines recommend Methotrexate (MTX) with or without glucocorticoids (GCs) for DMARD naïve patients. Triple DMARD therapy however is not recommended in these guidelines, because well proven evidence of superior...

SAT0130 Defining the Optimal Biological Monotherapy in Rheumatoid Arthritis (RA): Network Meta-Analysis of Randomized Trials

BackgroundMethotrexate (MTX) is considered the anchor drug in RA, both as monotherapy, as well as for its ability to increase the efficacy of biologic agents when used in combination [1]....

SAT0049 Obesity is Associated with Reduced Improvement in Functional Disability After 1 Year of Treatment: Results from an Inception Early Rheumatoid Arthritis Cohort

BackgroundDisease outcomes in rheumatoid arthritis (RA) may be influenced by a patient’s body mass index (BMI). Previous work has shown improved radiographic outcomes in obese RA patients1. However, obesity is...

SAT0304 Long-Term Costs of Biologics in the Treatment of Psoriatic Arthritis in the United States

BackgroundThe introduction of biologic therapies has dramatically changed the management of psoriatic arthritis (PsA), however, these therapies are more expensive than previous treatments. To our knowledge, there is little information...

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...

AB0363 Coadministration of asp015k, a novel janus kinase inhibitor, with methotrexate demonstrates tolerability and lack of pharmacokinetic interactions in patients with rheumatoid arthritis

BackgroundASP015K is an oral Janus kinase (JAK) inhibitor with selectivity for JAK1/3 in development for treatment of rheumatoid arthritis (RA) and other autoimmune diseases. Methotrexate (MTX) is the most common...

PMS11 - Meta-Analysis For Efficacy Of Etanercept For Treatment Of Psoriatic Arthritis

Psoriatic arthritis (PA) is an inflammatory disease affecting joints and connective tissues. The anti-tumor necrosis factor (TNF) biologics are increasingly being used in patients who have failed traditional disease-modifying antirheumatic drugs. Etanercept has shown efficacy in treatment of PA. The objective of this study was to conduct meta-analysis and present total evidence for etanercept in treatment of PA. For this meta-analysis we included randomized controlled trials (RCTs)evaluating etanercept for the treatment of PS. RCTs studying adult populations with active and progressive PA with an inadequate response to previous DMARD therapy were eligible. Trials conducted among PA populations with prior experience with anti-TNF agents, including an inadequate response, were excluded. A systematic literature search for Etanercept trials was undertaken for the databases Pubmed, Embase, Biosis, Google Scholar, and Cochrane. Data was collected for the study size, interventions, year, and the three outcomes HAQ, PASI and PsARC. For meta-analysis, random effects and fixed effects models were used to obtain cumulative statistics. Two RCTs with a total of 131 patients were identified. The pooled response rates for Etanercept for PsARC were 75% (95% CI 60%-90%), for HAQ were 59% (95% CI 46%-72%), and for PASI were 24% (95% CI 13%-34%). The pooled response rates for placebo for PsARC were 30% (95% CI 26%-35%), for HAQ were 5% (95% CI 1%-9%), and for PASI were 3% (95% CI 0%-7%). For PsARC the cumulative relative risk with Etanercept versus placebo was 0.40 (95% CI 33%-48%). For HAQ, the cumulative relative risk with Etanercept versus placebo was 0.08 (95% CI 5%-12%). For PASI, the cumulative relative risk with Etanercept versus placebo was 0.14 (95% CI 8%-20%). Meta-analysis shows Etanercept offers patients with psoriatic arthritis an effective therapeutic option for control of their disease

Treatment preferences in juvenile idiopathic arthritis – a comparative analysis in two health care systems

BackgroundVariations in the treatment of juvenile idiopathic arthritis (JIA) may impact on quality of care. The objective of this study was to identify and compare treatment approaches for JIA in two health care systems.MethodsPaediatric rheumatologists in Canada (n=58) and Germany/Austria (n=172) were surveyed by email, using case-based vignettes for oligoarticular and seronegative polyarticular JIA. Data were analysed using descriptive statistics; responses were compared using univariate analysis.ResultsTotal response rate was 63%. Physicians were comparable by age, level of training and duration of practice, with more Canadians based in academic centres. For initial treatment of oligoarthritis, only approximately half of physicians in both groups used intra-articular steroids. German physicians were more likely to institute DMARD treatment in oligoarthritis refractory to NSAID (p<0.001). Canadian physicians were more likely to switch to a different DMARD rather than a biologic agent in polyarthritis refractory to initial DMARD therapy. For oligoarthritis and polyarthritis, respectively, 86% and 90% of German physicians preferred regular physiotherapy over home exercise, compared to 14% and 15% in Canada. Except for a Canadian preference for naproxen in oligoarthritis, no significant differences were found for NSAID, intra-articular steroid preparations, initial DMARD and initial biologic treatment.ConclusionsTreatment of oligo- and polyarticular JIA with DMARD is mostly uniform, with availability and funding obviously influencing physician choice. Usage of intra-articular steroids is variable within physician groups. Physiotherapy has a fundamentally different role in the two health care systems.

Triple DMARD combination for rheumatoid arthritis resistant to methotrexate and steroid combination: a single-center experience

The mainstay of RA treatment is the disease-modifying antirheumatic drugs, and triple DMARD combination is now known to be better than monotherapies. Our aim in this trial was to report our clinical experience with triple DMARD therapy for resistant rheumatoid arthritis. Data of 140 patients with RA resistant to methotrexate and steroid combination were evaluated retrospectively. One hundred and nineteen (85 %) were female, and the median age at diagnosis was 56 (29-82) years. The median time between the diagnosis and beginning of triple therapy was 45.5 (6-564) months. Fifty-two (37.1 %) patients (group 1) on triple therapy protocol achieved remission, but the others (88; 62.9 %) (group 2) did not. The mean DAS28 scores for the study group before triple DMARD therapy and after 12 months under triple DMARD therapy were 4.93 and 3.24, respectively. The DAS28 scores after 12 months for groups 1 and 2 were 2.57 and 3.64. The median follow-up period for patients in group 1 was 60 months (23-118), and the mean DAS28 score at the time of the analysis for group 1 was 2.36. Triple DMARD combination may save one-third of the MTX-resistant RA patients from the serious side effects and the cost of anti-TNF.

PMS47 The Health and Economic Consequences of Delay in Starting Disease-Modifying Antirheumatic Drugs (DMARDs) in Rheumatoid Arthritis

THE HEALTH AND ECONOMIC CONSEQUENCES OF DELAY IN STARTING DISEASE-MODIFYING ANTIRHEUMATIC DRUGS (DMARDS) IN RHEUMATOID ARTHRITIS Van doornum S1, Roberts L2, Reed MD3, Liew D1 1The University of Melbourne, Parkville, Vic, Australia, 2James Cook University, Douglas, Queensland, Australia, 3Sir Charles Gairdiner Hospital, Nedlands, Western Australi, Australia OBJECTIVES: Several international studies suggest that the time between symptom onset and DMARD initiation in RA patients is longer than is considered optimal. We sought to assess the health economic impact of this delay in an Australian context. METHODS: The delay in DMARD initiation was estimated from a 2005 study of 96 Australian RA patients referred to one public and four private rheumatology practices. RA-associated utilities and costs were sourced from published data. Patients not taking and taking DMARD therapy were assumed to have utilities of 0.443 and 0.543, respectively. The annual direct costs of RA, excluding DMARDs, was AUD $3780, and of DMARD therapy was $2658. It was conservatively assumed that DMARD therapy did not reduce non-DMARD RA costs. RESULTS: In the 2005 study, the mean time from symptom onset to initiation of DMARD therapy was 1.48 years. Over this time a mean of 0.65 QALYs would have been lived per patient and $5579 of direct health care costs incurred. Had DMARDs been commenced at symptom onset, 0.80 QALYs would have been lived per patient, and $9503 of direct health care costs incurred. Hence early initiation of DMARDs would have saved 0.15 QALYs at a cost of $3924 per person, equating to an incremental cost-effectiveness ratio (ICER) of $26,583 per QALY saved. An additional $3400 could be spent per patient to reduce the time to DMARD initiation before the ICER breached the arbitrary cut-off of $50,000 per QALY saved. Our analysis was conservative in it did not consider the long-term health and cost savings associated with avoidance of permanent joint damage. CONCLUSIONS: The considerable delay in the initiation of DMARD therapy among patients with RA leads to significant health loss. Reducing the time to initiation of DMARDs represents a cost-effective means of reducing the burden of RA.

Relative importance of doctor-reported outcomes vs patient-reported outcomes in DMARD intensification for rheumatoid arthritis: the DUO study

For optimal RA management, the current recommendation is to adapt DMARD therapy to the level of inflammation and not only of patient complaints. We designed the DUO (epidemiological study of treatment decison in RA: DROs and PROs) study to assess the relative weight of patient-reported outcomes (PROs) and doctor-reported outcomes (DROs) in DMARD intensification in RA patients. This French, observational, multicentre, cross-sectional study was conducted in 2009 on RA patients included by rheumatologists. The percentage of patients with DMARD intensification was evaluated with regard to the concomitant DAS28-ESR and Patient Acceptable Symptom State (PASS) questionnaire assessments. Logistic regression was used to find significant criteria of DMARD intensification. The relative weight of subjective/objective criteria was assessed using attributable risk fractions. A total of 1107 patients were analysed (76% women; median disease duration 6 years); DMARD intensification was proposed to 15% of patients (24% of patients with DAS >3.2 and 33% of patients with non-acceptable PASS). DMARD intensification determinants comprised both DROs (high tender and swollen joint counts) and PROs (high patient global assessment of disease activity), but also short disease duration and rheumatologist characteristics (young, hospital based). Respectively, 61% and 42% of DMARD intensification were attributable to PROs and DROs. The DUO study showed DMARD intensification was predominantly based on PROs compared with DROs and influenced by disease duration and type of rheumatology practice. Most RA patients with DAS28 >3.2 had no DMARD intensification.

Automated radiofrequency-based US measurement of common carotid intima-media thickness in RA patients treated with synthetic vs synthetic and biologic DMARDs

To compare the carotid intima-media thickness (IMT) assessed with automated radiofrequency-based US in RA patients treated with synthetic vs synthetic and biologic DMARDs and controls. Ninety-four RA patients and 94 sex- and age-matched controls were prospectively recruited at seven centres. Cardiovascular (CV) risk factors and co-morbidities, RA characteristics and therapy were recorded. Common carotid artery (CCA)-IMT was assessed in RA patients and controls with automated radiofrequency-based US by the same investigator at each centre. Forty-five (47.9%) RA patients had been treated with synthetic DMARDs and 49 (52.1%) with synthetic and biologic DMARDs. There were no significant differences between the RA patients and controls in demographics, CV co-morbidities and CV disease. There were significantly more smokers among RA patients treated with synthetic and biologic DMARDs (P = 0.036). Disease duration and duration of CS and synthetic DMARD therapy was significantly longer in RA patients treated with synthetic and biologic DMARDs (P < 0.0005). The mean CCA-IMT was significantly greater in RA patients treated only with synthetic DMARDs than in controls [591.4 (98.6) vs 562.1 (85.8); P = 0.035] and in RA patients treated with synthetic and biologic DMARDs [591.4 (98.6) vs 558.8 (95.3); P = 0.040). There was no significant difference between the mean CCA-IMT in RA patients treated with synthetic and biologic DMARDs and controls (P = 0.997). Our results suggest that radiofrequency-based measurement of CCA-IMT can discriminate between RA patients treated with synthetic DMARDs vs RA patients treated with synthetic and biologic DMARDs.

The US7 score is sensitive to change in a large cohort of patients with rheumatoid arthritis over 12 months of therapy

PurposeTo determine the sensitivity to change of the US7 score among RA patients under various therapies and to analyze the effect of each therapeutic option over 1 year. To estimate...

Phase III trial results for tofacitinib bring new oral DMARD therapy a step closer for patients with rheumatoid arthritis

Clinical trials: Phase III trial results for tofacitinib bring new oral DMARD therapy a step closer for patients with rheumatoid arthritis

Intracellular signaling transduction pathways

Even though biologics, frequently combined with conventional DMARD therapy, represent a significant advance in the treatment of rheumatic diseases, they have disadvantages such as high costs of production and parenteral administration. Therefore, oral small-molecule drugs are a potential alternative. Major targets for such small-molecule therapeutics are intracellular signaling molecules. This article will briefly discuss potential intracellular targets for therapeutics in the field of rheumatic diseases. How therapeutic signaling inhibitors will be used in clinical practice will depend on a number of factors: their overall effectiveness, their effectiveness in patients who did not or insufficiently respond to conventional DMARD therapy and/or treatment with biologics, their effectiveness when combined with other therapeutics, their side effects, and their cost-benefit ratio.The English full-text version of this article is available at SpringerLink (under "Supplemental").

Naive to Biologic Therapy or Inadequate Responders to TNF- Inhibitors: A Phase 2 Study of LY2439821

Evidence from both animal and human models regarding the proinflammatory cytokine interleukin-17 (IL-17) and the T-helper cell (Th17) that secretes it provides a compelling rationale for therapeutic targeting of IL-17 in rheumatoid arthritis (RA). Ixekizumab (LY2439821) is a humanized monoclonal antibody that is used in the treatment of autoimmune diseases [Peck A and Mellins ED. Infect Immun 2010; Sarkar S and Fox DA. Rheum Dis Clin North Am 2010]. This article presents results from an international Phase 2, 2 Dose-Ranging Study of Multiple Subcutaneous Doses of LY2439821 in Patients With Active Rheumatoid Arthritis on Concomitant DMARD Therapy [NCT00966875].

Treatment Strategies in Early Rheumatoid Arthritis and Prevention of Rheumatoid Arthritis

Data now suggest that current strategies in the treatment of rheumatoid arthritis (RA) should focus on early identification and diagnosis, followed by early initiation of DMARD therapy. Initiation of treatment in early RA-ideally, less than 3-6 months after symptom onset-improves the success of achieving disease remission and reduces joint damage and disability. While the optimal treatment regimen in early RA is unclear, use of initial DMARD mono- or combination therapy with prompt escalation to achieve low disease activity or remission is an appropriate approach. Ultimately, the goal of RA management should be the prevention of inflammatory joint disease and, thereby, prevention of disability. To date, studies have shown that pharmacologic interventions can delay progression from undifferentiated inflammatory arthritis to classifiable RA. However, further investigation is needed to identify asymptomatic individuals at high risk for future RA and to intervene early enough in the pathogenesis of RA to prevent progression to clinical disease.

Economic benefits of optimizing anchor therapy for rheumatoid arthritis

The total cost of RA is substantial, particularly in patients with high levels of disability. There are considerable differences in cost between countries, driven in part by differences in the use of biologic therapies. Economic evaluations are needed to assess the extra cost of using these treatments and the benefits obtained, to ensure appropriate allocation of limited health care resources. The BeSt trial, evaluating four treatment strategies, found comparable medium-term efficacy but substantially higher costs with early biologic therapy. A systematic review of such cost-effectiveness analyses concluded that biologic therapy should be used after therapy has failed with less costly alternatives such as synthetic DMARDs and glucocorticoids. Optimizing such relatively low-cost therapy to improve outcomes may delay the need for biologic therapy, thereby saving costs. A simple model has confirmed the value of this approach. The addition of modified-release prednisone 5 mg/day to existing synthetic DMARD therapy in patients with active disease resulted in improvement in DAS-28 to below the threshold level for initiation of reimbursed biologic therapy in 28-34% of patients. On a conservative estimate (i.e. assuming no further benefits beyond the 12 weeks of the study and a 12-week wait-and-see approach to starting biologic therapy), cost savings amounted to nearly € 400 per patient. While treatment decisions should never be based only on cost considerations, prolonging disease control by optimizing the use of non-biologic treatments may bring benefits to patients and also economic benefits by delaying the need for biologic treatments.

Disease control with glucocorticoid therapy in rheumatoid arthritis

DMARDs aim to improve long-term prognosis of RA, as indicated by reduced progression of radiographic damage and maintenance of function. However, it may be more appropriate to consider disease-modifying strategies rather than drugs alone. Despite the challenges (e.g. lack of standard outcome measures, poor reporting of dose levels), a systematic review of 15 studies involving more than 1400 patients showed that glucocorticoid treatment for 1-2 years slowed radiographic progression compared with control treatment. Evidence for longer term disease-modifying benefits of glucocorticoids comes from individual studies with extended follow-up. In the Utrecht study, patients with early RA originally assigned to prednisone 10 mg/day for 2 years and then tapered off the therapy showed significantly less radiographic progression at follow-up after a further 3 years than patients originally assigned placebo, with no significant difference in the use of synthetic DMARD therapy. In the combination therapy in early RA (COBRA) study, patients with newly diagnosed RA treated with glucocorticoid (starting with 60 mg/day, quickly reduced to 7.5 mg/day for weeks 7-28 and subsequently stopped), MTX up to week 40 and SSZ showed significantly decreased radiographic progression compared with those treated with SSZ alone. The benefits of short-term combination therapy on disease progression were still apparent at 5-year and 11-year follow-up. In conclusion, there is clear evidence that treatment regimens including low-dose glucocorticoids given early in RA slow radiographic progression, meeting the definition of a DMARD. Furthermore, the evidence suggests that such treatment strategies favourably alter the disease course even after glucocorticoid discontinuation.

PMS88 Mixed Treatment Comparison, Cost-Effectiveness Analysis and Budget Impact Model in the Treatment of Rheumatoid Arthritis After Failure of Conventional Dmard Therapy Using Comprehensive Bayesian Decision Analytical Modelling

PMS88 Mixed Treatment Comparison, Cost-Effectiveness Analysis and Budget Impact Model in the Treatment of Rheumatoid Arthritis After Failure of Conventional Dmard Therapy Using Comprehensive Bayesian Decision Analytical Modelling