Traditional Disease-modifying Antirheumatic Drugs Research Articles

Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis

Objective To compare methotrexate based disease modifying antirheumatic drug (DMARD) treatments for rheumatoid arthritis in patients naive to or with an inadequate response to methotrexate.Design Systematic review and Bayesian random...

Rheumatoid arthritis is still expensive in the new decade: a comparison between two early RA cohorts, diagnosed 1996–98 and 2006–09

Objectives: To calculate total costs during the first year after diagnosis in 463 patients with early rheumatoid arthritis (RA) included during 2006–09 (T2) and compare the results with a similar cohort included in 1996–98 (T1).Method: Clinical and laboratory data were collected regularly in both cohorts, and patients completed biannual questionnaires reporting health care utilization and number of days lost from work.Results: Disease activity was similar in both cohorts T1 and T2 at inclusion. Significant improvements were seen during the first year in both cohorts but were more pronounced in T2. Outpatient care increased and hospitalization decreased in T2 compared with T1. Almost 3% of patients had surgery in both cohorts, but in T2, only women had surgery. Drug costs were higher in T2 than in T1 (EUR 689 vs. EUR 435). In T2, 12% of drug costs were direct costs and 4% were total costs. The corresponding values for T1 were 9% and 3%. In T1, 50% were prescribed disease-modifying anti-rheumatic drugs (DMARDs) at inclusion, compared to T2, where prescription was > 90%. Direct costs were EUR 5716 in T2 and EUR 4674 in T1. Costs for sick leave were lower in T2 than in T1 (EUR 5490 vs. EUR 9055) but disability pensions were higher (EUR 4152 vs. EUR 2139), resulting in unchanged total costs. In T1, direct costs comprised 29% and indirect costs 71% of the total costs. The corresponding values for T2 were 37% and 63%.Conclusions: The earlier and more aggressive treatment of RA with traditional DMARDs in T2 resulted in better outcomes compared to T1. Direct costs were higher in T2, partly offset by decreased sick leave, but total costs remained unchanged.

COURSE OF UVEITIS IN PATIENTS WITH ANKYLOSING SPONDYLITIS

Relapsing uveitis is a serious problem for patients with ankylosing spondylitis (AS). Tumor necrosis factor- α inhibitors significantly reduce the frequency of uveitis attacks in AS patients, but they are not always available. In this connection, it is appropriate to evaluate the effect of traditional disease-modifying antirheumatic drugs on the course of uveitis in AS. Objective: to compare the frequency of uveitis attacks in AS during combined therapy using sulfasalazine (SULF) and nonsteroidal anti-inflammatory drugs (NSAIDs) versus monotherapy with NSAIDs. Subjects and methods. A total of 111 patients with significant AS who had at least one uveitis attack during the disease were examined. 49 subjects received combined therapy including SULF 2 grams daily and NSAIDs for at least 1 year. Six of the 49 patients were noted to have frequently relapsing uveitis (above 3 episodes yearly); 43 had no more than 3 ones per year. The remaining 62 patients took NSAIDs only throughout the follow-up period. Nine of them had an average of 3 uveitis attacks per year; 53 had no more than 3 ones per year. Out of the 49 patients receiving combined therapy with NSAIDs and SULF, 23 took NSAIDs only at least 1 year before SULF use; 10 of them were observed to have frequent relapses in that period and 13 had three or fewer episodes. Results and discussion. The entire group showed an average of 2.06±2.04 uveitis attacks per year during monotherapy with NSAIDs and 1.41±1.83 attacks yearly during combined therapy with NSAIDs and SULF (p = 0.08). Among the patients with less than 3 uveitis attacks per year, the mean number of episodes was significantly fewer during combined therapy than during NSAID monotherapy: 0.99±0.87 and 1.37±0.91, respectively (p = 0.04). Among those with frequently relapsing uveitis (more than 3 attacks per year), the mean number of episodes yearly was not significantly different during NSAID monotherapy and combined therapy: 5.7±2.5 and 5.5±2.7, respectively (p = 0.9). In a subgroup of patients receiving sequentially NSAID monotherapy and combined therapy with NSADs and SULF, 13 patients with three or fewer baseline attacks per year displayed a significant reduction in the frequency of episodes from 1.92±0.96 to 0.4±0.44 (p = 0.00003). During combined therapy versus monotherapy, 10 patients with frequently relapsing uveitis (over 3 episodes yearly) exhibited an insignificant reduction in the number of relapses from 5.9±3.02 to 5.33±1.1 (p = 0.6). Conclusion. Combined therapy with SULF and NSAIDs does not substantially affect the frequency of uveitis episodes in AS patients with frequently relapsing uveitis (above 3 attacks per year), but significantly reduces the number of episodes among patients with its mild course (less than 3 attacks yearly).

Cost-Effectiveness Analysis of Tocilizumab in Comparison with Infliximab in Iranian Rheumatoid Arthritis Patients with Inadequate Response to tDMARDs: A Multistage Markov Model

ObjectivesTo analyze the cost-effectiveness of two common treatment strategies in Iran, comparing infliximab plus methotrexate with tocilizumab plus methotrexate in patients with rheumatoid arthritis with inadequate response to traditional disease-modifying antirheumatic drugs. MethodsA multistage Markov decision model was applied to assess the incremental cost-effectiveness ratio (ICER) of a tocilizumab-containing regimen versus an infliximab-containing regimen over a 5-year time period. In the case of no response, we assumed that patients switched to the next treatment (adalimumab, rituximab, or supportive care) in sequence for each strategy. We considered major cost items, such as direct medical costs and direct nonmedical costs, from a payer (patients and third-party payers) perspective. A deterministic sensitivity analysis was conducted to assess the robustness of the model results over the uncertainty of key parameters. ResultsIn the base-case analysis, the ICER of the tocilizumab-containing regimen was US $60,800 per quality-adjusted life-year as compared to the infliximab-containing regimen. In the sensitivity analysis, changes in the price of the drugs by generic substitution, in utility scores, and in discount rate did not change our overall conclusions. Among all inputs to the primary study and the sensitivity analyses, however, the price of tocilizumab had the most impact on the ICER. ConclusionsAlthough tocilizumab and methotrexate provide a larger gain in quality-adjusted life-years, their current price is quite high as compared with those of our other interventions. Therefore, a regimen containing tocilizumab is not cost-effective as compared with an infliximab-containing regimen for patients with rheumatoid arthritis in Iran.

Acute Lymphoid Leukemia After Anti-TNF-alpha Treatment: A Case Report and Review of the Literature

The efficacy and safety of anti-tumor necrosis factor-alpha drugs have been shown in active ankylosing spondylitis cases that are resistant to traditional disease-modifying antirheumatic drugs. However, it is well known that these drugs may cause some complications as reactivation of tuberculosis and various hematologic malignancies. In this article, we report a 40-year-old male patient with ankylosing spondylitis who developed Philadelphia chromosome-positive acute lymphoid leukemia after treatment with tumor necrosis factor-alpha inhibitors.

2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis

To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.

To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

The Definition and Measurement of Axial Psoriatic Arthritis.

This review seeks to update the state of the art of axial psoriatic arthritis (axPsA). The definition and assessment of axPsA can be problematic because no agreement and no definitive data on this topic have been published, resulting in uncertainty as to the best approach to deal with these patients. A few recent scientific reports show new data on the possible coincidence of diffuse idiopathic skeletal hyperostosis and axPsA, as well as on the radiological assessment as measured with the validated instruments for axPsA. Moreover, the role of magnetic resonance imaging has also been evaluated for this intriguing subset. All data confirmed that radiological assessment is a useful tool to detect typical findings of axPsA, while other imaging techniques remain to be validated. Finally, there is no evidence to support treatment of axPsA with traditional disease-modifying antirheumatic drugs, while a "leap" to biologic agents is the only treatment after failure with nonsteroidal antiinflammatory drugs.

Iguratimod in combination with methotrexate in active rheumatoid arthritis : Therapeutic effects.

Rheumatoid arthritis (RA) is a potentially destructive disease that may have a profound impact on patients' function and quality of life. RA therapy is still a challenge for rheumatologists; however, new antirheumatic drugs may be a treatment option for disease-modifying antirheumatic drug (DMARD)-experienced patients with active RA. The present study is a prospective trial that aims to investigate the effects of therapy with iguratimod plus methotrexate (MTX) in comparison with iguratimod or MTX monotherapy in DMARD-experienced adult patients with active RA. A total of 131patients (24 men, 107 women, mean age 46.63 ± 10.61 years) with a history of being treated with traditional DMARDs were investigated. In all, 44patients were treated with iguratimod (25mg, twice daily, orally) plus MTX (a weekly dose of 10mg, orally), 38patients received iguratimod (25mg, twice daily, orally), or 49patients received MTX (weekly dose of 10mg, orally) for 24weeks. A therapeutic effect with iguratimod was observed between 4 and 10 weeks after treatment initiation and was effective even in patients who had a poor response to previous treatment with DMARDs. The combination of iguratimod with MTX was superior to iguratimod or MTX monotherapy. The data imply that iguratimod is a welcome addition to the small-molecule drug therapy for DMARD-experienced patients with active RA. Iguratimod (alone or in combination with MTX) is an emerging option for the treatment of DMARD-experienced adult patients with active RA who have had an inadequate response to or are intolerant of other DMARDs.

PMS135 - Characteristics of Patients Starting Biologic Treatments for Rheumatoid Arthritis in The Real World: Systematic Review

To assess demographic and disease characteristics of rheumatoid arthritis (RA) patients starting treatment with biologic disease-modifying anti-rheumatic drugs (DMARDs) in observational studies. Systematic review of published observational studies in adult patients with RA treated with one of three biologic DMARDs (etanercept, rituximab, tocilizumab). We identified eligible studies through electronic searches of the MEDLINE and EMBASE databases. Two reviewers screened the articles independently. We extracted study characteristics such as location and calendar period, demographics of study populations, dose, frequency and concomitant therapies, and baseline characteristics such as disease duration, disease activity and lab measurements. 106 papers met our inclusion criteria. Studies were published between 2003 and 2015 and mostly from Europe; 39 included patients starting etanercept, 36 included patients starting rituximab and 32 patients starting tocilizumab. Mean age ranged between 42.9 and 63.3 years, 78.2% were female. The drugs were given in combination with methotrexate and/or other traditional DMARDs in over two thirds of the studies. Mean disease duration varied between 4 and 17.5 years, baseline disease activity 28 scores between 4.3 and 7.0, and baseline health assessment questionnaire values between 1 and 2.9. The mean percentage of rheumatoid-factor positive patients was 76.4%. Reporting of comorbidities and smoking status was generally poor, with only few studies providing detailed data. This systematic review of data from observational studies and clinical databases indicates that the characteristics of RA patients starting biological DMARDs outside clinical trials in the real world varied widely. These observational data will now be compared with clinical trial data but it seems likely that some patient groups were not well represented in the trials.

Optimizing Methotrexate Treatment in Rheumatoid Arthritis: The Case for Subcutaneous Methotrexate Prior to Biologics.

Methotrexate is the most common disease-modifying antirheumatic drug (DMARD) used in the treatment of rheumatoid arthritis (RA). Current evidence supports its efficacy in the treatment of RA, resulting in improved short-term disease control and long-term outcomes in terms of radiographic progression. Oral methotrexate has traditionally been used first-line due to various reasons, including ease of administration, low cost and easy availability. A methotrexate dose of >15 mg/week is generally required for disease control but oral methotrexate may be only partially effective or poorly tolerated in some patients. The rationale for using subcutaneous (SC) methotrexate is based on its improved bioavailability at higher doses and better tolerability in some patients who have side effects when receiving oral methotrexate. Current guidance advocates 'treating to target', with the aim of inducing remission in RA patients. In some patients, this can be achieved using methotrexate alone or in combination with other traditional DMARDs. Patients who have not responded to two DMARDs, including methotrexate, are eligible for biological therapy as per current National Institute for Health and Care Excellence (NICE) guidance in the UK. Biological treatments are expensive and using SC methotrexate can improve disease control in RA patients, thus potentially avoiding or delaying the requirement for future biological treatment.

Indirect comparisons of the efficacy of biological agents in patients with psoriatic arthritis with an inadequate response to traditional disease-modifying anti-rheumatic drugs or to non-steroidal anti-inflammatory drugs: A meta-analysis.

While the efficacy of biologic agents for the treatment of psoriatic arthritis (PsA) has been well demonstrated in randomized controlled trials (RCTs), the data on their relative efficacy is limited. This meta-analysis is aimed at assessing the comparative efficacy of these agents in patients who had persistently active disease despite traditional non-steroidal anti-inflammatory drugs (NSAIDs)/disease-modifying anti-rheumatic drugs (DMARDs), or who could not tolerate NSAIDs/DMARDs. RCTs examining the efficacy of biologic agents in patients with PsA who experienced inadequate response or intolerance of traditional DMARDs or NSAIDs were identified. If more than one RCT were available for a given biologic agent, the pooled risk ratio (RR) and 95% confidence interval (CI) of attaining a 20% improvement according to American College of Rheumatology criteria (ACR20) response across trials were calculated. The pooled risk ratios for each biologic agent were then compared using the indirect comparison technique. A total of 12 RCTs were identified and included in the data analyses. We found that patients who received older TNF inhibitors (etanercept, infliximab, adalimumab, and golimumab) had a statistically significantly higher chance of achieving ACR20 response compared with apremilast, ustekinumab, and certolizumab. The likelihood of achieving ACR20 response among secukinumab users (at the dose of 150 mg and 300 mg weekly) was also higher compared with apremilast, ustekinumab, and certolizumab, though the relative risk did not always reach statistical significance. Our study demonstrates that patients with PsA who experience inadequate response or intolerance of traditional DMARDs or NSAIDs have a higher probability of achieving the ACR20 response with older TNF inhibitors and secukinumab.

Pharmacological treatment of spondyloarthritis: exploring the effectiveness of nonsteroidal anti-inflammatory drugs, traditional disease-modifying antirheumatic drugs and biological therapies.

Spondyloarthritis represents a heterogeneous group of articular inflammatory diseases that share common genetic, clinical and radiological features. The therapy target of spondyloarthritis relies mainly in improving patients' quality of life, controlling articular inflammation, preventing the structural joints damage and preserving the functional abilities, autonomy and social participation of patients. Among these, traditional disease-modifying antirheumatic drugs have been demonstrated to be effective in the management of peripheral arthritis; moreover, in the last decade, biological therapies have improved the approach to spondyloarthritis. In patients with axial spondyloarthritis, tumor necrosis factor α inhibitors are currently the only effective therapy in patients for whom conventional therapy with nonsteroidal anti-inflammatory drugs has failed. The aim of this review is to summarize the current experience and evidence about the pharmacological approach in spondyloarthritis patients.

X-RAY PROGRESSION AND ITS IMPACT ON THE FUNCTIONAL STATUS OF PATIENTS WITH EARLY RHEUMATOID ARTHRITIS DURING A 5-YEAR FOLLOW-UP

Objective: to assess progression of X-ray joint changes and their impact on functional status of patients with early rheumatoid arthritis (RA). Subjects and methods. The investigation enrolled 204 patients with early RA included in the RADICAL (Early Arthritis: Diagnosis, Outcomes, Criteria, Active Treatment) program in the period 2003 to 2007. The duration of the disease at the inclusion was less than 2 years. RA was diagnosed according to 1987 American College of Rheumatology (ACR) criteria. Rheumatoid factor was presentin 67.5% of the patients and anti-cyclic citrullinated peptide antibodies – in 57%. Women were 86.5%; median age was 49 [40; 58] years. The patients received traditional diseasemodifying antirheumatic drugs and biological agents (24%). Therapy response was monitored applying the tight control strategy. Main clinical and laboratory parameters, DAS28, and HAQ scores, and functional class and hand and foot X-ray were recorded every year. Results and discussion . After 5 years of follow-up, new erosions appeared in 57% of the patients. Joint erosions were present in 16.5% of the patients at the inclusion and in 73% following 5 years. At baseline, after 1, 2, 3, 4, and 5 years, the total erosion scores (modified Sharp score) was equal to 0 [0; 0], 0 [0; 1], 0 [0; 4], 1 [0; 8], 3 [0; 12], 6 [0; 14], respectively. A significant functional improvement could be achieved just during the first year of follow-up. Thus, the median HAQ value decreased from 1.125 [0.625; 1.75] to 0.5 [0.125; 1.0], reaching the population level. Following 2, 3, 4, and 5 years, the median HAQ was 0.5 [0; 1.0], 0.5 [0; 1.0], 0.5 [0; 1.0], and 0.75 [0.125; 1.125], respectively. There was a weak positive correlation between total erosion scores and HAQ in the eаrly stage of the disease. However, it became more marked after 3, 4, and 5 years (correlation coefficient, 0.38, 0.39, and 0.40, respectively; p < 0.01). Conclusion. In spite of the stable pattern of disease course, structural damage progression was seen in patients with early RA. However, detailed erosive component assessment using the modified Sharp score showed that the structural changes were modest in the majority of patients and HAQ value during the first 4 years of follow-up were comparable with the population level, which may be indicative of a rather favorable functional prognosis. Five years later, there was an increasing correlation between total erosion scores and HAQ. This may be responsible for higher HAQ scores after 5 years of follow-up

Management of Psoriatic Arthritis

Traditional disease-modifying antirheumatic drugs (DMARD) remain the first-line treatment of psoriatic arthritis (PsA), despite lack of randomized controlled trials, and with evidence based on observational studies. Anti-tumor necrosis factor agents remain a top choice for biologic treatment, complemented with new biologics with different targets (IL12-23 and IL17). Unmet needs have been identified for patients who do not respond to treatment. Among targeted small molecules Apremilast is approved for the treatment of PsA and Tofactitinib is under investigation. The drugs discussed herein have the potential to address unmet needs; however, additional research is required to identify more effective therapies for PsA.

Impact of Etanercept Therapy on Disease Activity and Health-Related Quality of Life in Moderate Rheumatoid Arthritis Patients Population from a National British Observational Cohort

ObjectivesTo describe a population with moderate rheumatoid arthritis (RA) before biologic initiation and assess change in disease status, health-related quality of life (HRQOL), and adverse events in etanercept (ETN)-treated patients. MethodsData on adult patients with moderate RA (3.2 < Disease Activity Score in 28 Joints [DAS28] ≤ 5.1) were retrospectively analyzed from the British Society for Rheumatology Biologics Register comparing a nonbiologic-treated group (nBG) using at least one traditional disease-modifying antirheumatic drug to a biologic group (BG) treated with ETN. The HRQOL was assessed by using the Health Assessment Questionnaire disability index score. To mitigate confounding, we controlled for drivers of progression. Appropriate univariate, multivariate, and regression analyses were used. ResultsA total of 1754 patients with RA were assessed (211 BG and 1543 nBG). Compared with the nBG, the BG tended toward higher disease activity, such as significantly higher tender joints and DAS28. The BG compared with the nBG had 1) a greater reduction in DAS28 and Health Assessment Questionnaire scores; 2) disease remission occurring more often (odds ratio = 2.7; P = 0.006); and 3) progression occurring in fewer patients (odds ratio = 0.3; P = 0.002). BG patients had a higher incidence of “other serious infection” and “other central nervous system–related events,” with no significant differences in associated hospitalization rates or deaths. ConclusionsAmong patients with moderate RA from a clinical practice registry, ETN-treated patients had significantly higher disease activity at the time of biologic initiation but significantly reduced disease activity and better HRQOL after 6 months compared with nBG patients, although the possibility of unmeasured confounding remains. The ETN group reported significantly higher incidences of “other serious infections” and “other central nervous system–related events” without higher hospitalization rates.

Window of opportunity to achieve major outcomes in early rheumatoid arthritis patients: how persistence with therapy matters.

IntroductionBenefits of disease-modifying anti-rheumatic drugs (DMARD) in early rheumatoid arthritis patients (ERAP) will be achieved if patients follow prescribed treatment. Objective was to investigate whether timing of first non-persistence period and/or duration of persistence during the first 4 years of follow-up predicted disease outcomes at the 5th year in a cohort of ERAP, initiated in 2004.Patients and MethodsUp to February 2015, charts of 107 ERAP with at least 5 years of follow-up and prospective 6-month assessments of disease activity, disability and persistence were reviewed. Non-persistence was defined as omission of DMARD and/or corticosteroids for at least 7 consecutive days; regarding methotrexate, one weekly missing dose was considered non-persistence. Persistence was recorded through an interview (up to 2008) and thereafter through a questionnaire; persistence duration was recorded in months of continuous medicationtaking. At the 5th year, disease activity was defined according to Disease Activity Score (DAS)28, and disability according to Health Assessment Questionnaire (HAQ). Descriptive statistics and linear and Cox regression analyses were used.ResultsAt study entry, patients were more frequently middle-aged (39.1 ± 13.3 years) and female (88.8 %), as well as more likely to have high disease activity and disability. Over the first 4 years of follow-up, 54.2 % of the patients had indications for oral corticosteroids and all traditional DMARDs. Almost 70 % had at least one period of non-persistence, and their follow-up (median, 25th–75th interquartile range) to first non-persistence period was 13 months (1–31). Persistence duration during the first 4 years predicted subsequent DAS28 (in addition to gender and baseline DAS28) and HAQ (in addition to age). During the 5th year, 68 patients (56 women) achieved sustained remission (DAS28 < 2.6). In female population (n = 95), baseline DAS28 (odds ratio [OR], 0.65; 95 % confidence interval [CI], 0.50–0.83; p = 0.001) and persistence duration (OR, 1.04; 95 % CI, 1–1.08; p = 0.05) were predictors. Also, 84 patients achieved sustained function (HAQ <0.21), and baseline DAS28 and age were the only predictors. Timing of first non-persistence period did not impact outcomes.ConclusionsPersistence duration with DMARDs within the first 4 years of RA predicted subsequent favorable outcomes in ERAP; additional predictors were younger age, male gender and lower disease activity at diagnosis.

Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis.

BackgroundTo measure circulating anti-citrullinated peptide antibodies (ACPA) and cytokines pre- and 6 months post-therapy as a strategy to predict and optimize responses to traditional disease-modifying antirheumatic drugs (DMARDs) in early RA, which is an unmet need in developing countries.Patients and methodsA cohort of 140 predominantly (88.5 %) black female South African patients with early RA was treated with synthetic DMARDs, mostly methotrexate (MTX) alone, or in combination with low-dose oral corticosteroids (CS). Circulating ACPA and a panel of circulating cytokines/chemokines/growth factors were measured at baseline and after 6 months of therapy in relation to disease activity and Shared Epitope (SE).ResultsFollowing 6 months of therapy, the median simplified disease activity index (SDAI) declined from a baseline of 41.4 to 16.0 (p = 0.0001) for the entire cohort, which was paralleled by significant falls in median serum ACPA levels (516.6 vs. 255.7 units/ml, p = <0.0001) and several of the circulating cytokines (IL-4, IL-7, IL-8, G-CSF, VEGF; p < 0.0010 – p < 0.0001) which were most evident in the subgroup of patients treated with a combination of MTX and CS. Although biomarker concentrations decreased most notably in the low-disease activity group post-therapy, no significant correlations between these biomarkers and disease activity were observed, Baseline ACPA levels, but not SDAI or cytokines, were significantly higher in the subgroup of risk allele-positive patients (561.1 vs. 331.9 units/ml, p < 0.05), while no associations with ACPA and a smoking history were evident.ConclusionsThe use of DMARDs in RA is associated with significant decreases in ACPA and cytokines which did not correlate with changes in SDAI, precluding the utility of serial measurement of these biomarkers to monitor early responses to therapy, but may have prognostic value.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-015-0587-1) contains supplementary material, which is available to authorized users.

Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis

Serious infections are a major concern for patients considering treatments for rheumatoid arthritis. Evidence is inconsistent as to whether biological drugs are associated with an increased risk of serious infection compared with traditional disease-modifying antirheumatic drugs (DMARDs). We did a systematic review and meta-analysis of serious infections in patients treated with biological drugs compared with those treated with traditional DMARDs. We did a systematic literature search with Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to Feb 11, 2014. Search terms included "biologics", "rheumatoid arthritis" and their synonyms. Trials were eligible for inclusion if they included any of the approved biological drugs and reported serious infections. We assessed the risk of bias with the Cochrane Risk of Bias Tool. We did a Bayesian network meta-analysis of published trials using a binomial likelihood model to assess the risk of serious infections in patients with rheumatoid arthritis who were treated with biological drugs, compared with those treated with traditional DMARDs. The odds ratio (OR) of serious infection was the primary measure of treatment effect and calculated 95% credible intervals using Markov Chain Monte Carlo methods. The systematic review identified 106 trials that reported serious infections and included patients with rheumatoid arthritis who received biological drugs. Compared with traditional DMARDs, standard-dose biological drugs (OR 1.31, 95% credible interval [CrI] 1.09-1.58) and high-dose biological drugs (1.90, 1.50-2.39) were associated with an increased risk of serious infections, although low-dose biological drugs (0.93, 0.65-1.33) were not. The risk was lower in patients who were methotrexate naive compared with traditional DMARD-experienced or anti-tumour necrosis factor biological drug-experienced patients. The absolute increase in the number of serious infections per 1000 patients treated each year ranged from six for standard-dose biological drugs to 55 for combination biological therapy, compared with traditional DMARDs. Standard-dose and high-dose biological drugs (with or without traditional DMARDs) are associated with an increase in serious infections in rheumatoid arthritis compared with traditional DMARDs, although low-dose biological drugs are not. Clinicians should discuss the balance between benefit and harm with the individual patient before starting biological treatment for rheumatoid arthritis. Rheumatology Division at the University of Alabama at Birmingham.

Comparative Efficacy of Novel DMARDs as Monotherapy and in Combination with Methotrexate in Rheumatoid Arthritis Patients with Inadequate Response to Conventional DMARDs: A Network Meta-Analysis.

Given the availability of a number of alternative biologic treatment options and other novel disease-modifying antirheumatic drugs (DMARDs) for the treatment of patients with rheumatoid arthritis (RA), clinicians are faced with an increasingly challenging choice regarding optimal treatment. Biologics are usually combined with traditional DMARDs, primarily methotrexate (MTX), but some biologics and tofacitinib (together referred to in this article as novel DMARDs) have been shown to be efficacious as monotherapy as well. In real-world practice, approximately one-third of RA patients receiving biologics are on monotherapy, primarily because of intolerance of, or noncompliance with, MTX. Limited data, however, are available analyzing the effectiveness of monotherapy compared with combination therapy across novel DMARDs. To compare American College of Rheumatology (ACR) responses to approved novel DMARDs used as monotherapy or as combination therapy with methotrexate (MTX) at 24 weeks in RA patients who have shown inadequate response to conventional DMARDs (DMARD-IR). Through a systematic review of the literature, we identified randomized controlled trials that assessed approved novel DMARDs used as monotherapy or as combination therapy with MTX in DMARD-IR RA patients. Twenty-eight RCTs were identified that evaluated abatacept, anakinra, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, tocilizumab, or tofacitinib. ACR responses at 24 weeks were extracted and combined by means of Bayesian network meta-analyses. With the exception of anakinra plus MTX, which was less efficacious, most novel DMARDs, when used in combination with MTX, demonstrated comparable ACR responses. When novel DMARDs were used as monotherapies, greater ACR20/50/70 responses were observed with tocilizumab than with anti-tumor necrosis factor agents (aTNF) or tofacitinib. Furthermore, ACR20/50/70 responses with tocilizumab plus MTX were similar to those with tocilizumab monotherapy (odds ratio [OR] for the indirect comparison = 1.08, 95% credible interval [CrI] = 0.40-2.84; OR = 1.24, CrI = 0.44-3.61; OR = 0.95, CrI = 0.33-2.72, respectively), whereas greater responses were observed with aTNF plus MTX than with aTNF monotherapy (OR = 2.41, CrI = 0.51-11.61; OR = 2.85, CrI = 0.51-17.67; OR = 1.28, CrI = 0.21-8.42, respectively). Relative efficacy estimates for the indirect comparison of tofacitinib plus MTX with tofacitinib monotherapy were very uncertain. Results suggest that in combination with MTX most of the available novel DMARDs have similar levels of efficacy in DMARD-IR patients. As monotherapy, however, tocilizumab displayed higher ACR responses than aTNF or tofacitinib. ACR responses with tocilizumab plus MTX were similar to those with tocilizumab as monotherapy, whereas aTNF in combination with MTX demonstrated greater ACR responses than aTNF as monotherapy.