DMARDs In Rheumatoid Arthritis Research Articles

Comparison of active tuberculosis occurrence associated with Janus kinase inhibitors and biological DMARDs in rheumatoid arthritis

ObjectivesThis study aimed to evaluate the risk of tuberculosis associated with the use of Janus kinase (JAK) inhibitors or biological disease-modifying antirheumatic drugs (bDMARDs) in patients diagnosed with rheumatoid arthritis...

Complementary Therapies and Their Association with Problems in Therapeutic Adherence to Conventional Synthetic DMARDs in Rheumatoid Arthritis: A Cross-Sectional Study.

The use of complementary therapies is highly prevalent among patients with rheumatoid arthritis (RA). Nevertheless, the use of complementary medicine could involve problems in the following of scientifically accepted treatments. To date, there is limited information regarding the association of nonconventional therapies with problems regarding compliance with the treatment. Therefore, the objective of this study was to identify whether the utilization of complementary therapies is associated with a high risk of problems regarding therapeutic adherence to conventional synthetic disease-modifying anti-rheumatic drugs (cs-DMARDs) in RA patients. A survey was performed with RA patients in an outpatient rheumatology clinic in a university hospital; the use of complementary therapies, as well as their type, was identified. To assess problems with therapeutic adherence, we used the four-item Morisky-Green scale. A comprehensive assessment of clinical and therapeutic characteristics was performed. Univariable and multivariable models were performed to identify the risk of problems with therapeutic adherence in users of complementary therapies. In total, 250 RA patients were included; 92% used complementary therapies. Of them, the most frequently used were herbal medicine (65%), homeopathy (64%), and cannabis and its derivatives (51%). In the univariable logistic regression analysis, the factors associated with problems in the therapeutic adherence to cs-DMARDs were age (p = 0.019), the presence of other comorbidities (p = 0.047), and the use of complementary therapies (p = 0.042). After controlling for potential confounders, the use of complementary therapies increased the risk of problems with therapeutic adherence to cs-DMARDs (adjusted OR = 2.84, 95% CI = 1.06-7.63, p = 0.037). We concluded that the use of complementary therapies increases the risk of problems with therapeutic adherence. Therefore, for physicians and healthcare professionals, the early identification of the use of nonconventional therapies in their RA patients is required, followed by a directed discussion with their patients about the risks and benefits to which they could be exposed to complementary therapies.

677 Do Flare-Ups in Systemic Disease Activity Correlate to Cervical Deformity in Patients With Rheumatoid Arthritis?

INTRODUCTION: Following the introduction of biological DMARDs in Rheumatoid Arthritis (RA) treatment, cervical spine deformity seems to be less prevalent in those patients. It seems that this vast decline in patients with Atlanto-axial Subluxation (AAS), Subaxial Subluxation (SAS) or Vertical Subluxation (VS) is correlated to better control of systemic disease activity (DAS). The aim of the current study is to correlate the frequency of flare-ups in DAS to cervical spine deformity. METHODS: 272 RA patients were included and cervical deformity (AAS and/or SAS) was observed in 108 patients. 84 (31%) patients were in remission at 10 years FU and 206 (75%) of patients reached remission at least once during 10 years FU. Patients with cervical spine deformity at 10 years had less flare-ups (1.26) in DAS than patients without cervical spine deformity (1.58; 95% CI: 0.013-0.627). RESULTS: So, even though the BeSt Trial was designed to optimize treatment, 40% of the patients still developed RA-associated cervical spine deformity. However, remarkably, patients with more flares had less cervical deformity. This may be explained by the treatment regimen that anti-inflammatory medication is augmented upon measuring a systemic flare-up. CONCLUSIONS: This raises the hypothesis that RA medication treatment regimes should not be solely aimed at DAS values, as they are currently defined, in order to avoid cervical deformity in RA in the long term.

Using real-world data to dynamically predict flares during tapering of biological DMARDs in rheumatoid arthritis: development, validation, and potential impact of prediction-aided decisions

BackgroundBiological disease-modifying antirheumatic drugs (bDMARDs) are effective in the treatment of rheumatoid arthritis. However, as bDMARDs may also lead to adverse events and are expensive, tapering them is of great clinical interest. Tapering according to disease activity-guided dose optimization (DGDO) does not seem to affect long term remission rates, but flares are frequent during this process. Our objective was to develop a model for the prediction of flares during bDMARD tapering using data from routine care and to evaluate its potential clinical impact.MethodsWe used a joint latent class model to repeatedly predict the probability of a flare occurring within the next 3 months. The model was developed using longitudinal data on disease activity (DAS28) and other routine care data from two clinics. Predictive accuracy was assessed in cross-validation and external validation was performed with data from the DRESS (Dose REduction Strategy of Subcutaneous tumor necrosis factor inhibitors) trial. Additionally, we simulated the reduction in number of flares and bDMARD dose when implementing the model as a decision aid during bDMARD tapering in the DRESS trial.ResultsData from 279 bDMARD courses were used for model development. The final model included two latent DAS28-trajectories, bDMARD type and dose, disease duration, and seropositivity. The area under the curve of the final model was 0.76 (0.69–0.83) in cross-validation and 0.68 (0.62–0.73) in external validation. In simulation of prediction-aided decisions, the mean number of flares over 18 months decreased from 1.21 (0.99–1.43) to 0.75 (0.54–0.96). The reduction in he bDMARD dose was mostly maintained, increasing from 54 to 64% of full dose.ConclusionsWe developed a dynamic flare prediction model, exclusively based on data typically available in routine care. Our results show that using this model to aid decisions during bDMARD tapering may significantly reduce the number of flares while maintaining most of the bDMARD dose reduction.Trial registrationThe clinical impact of the prediction model is currently under investigation in the PATIO randomized controlled trial (Dutch Trial Register number NL9798).

Real-Life Retention Rates and Reasons for Switching of Biological DMARDs in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis.

Aims: To determine real-life biologic/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) retention rates in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), explore reasons for switching and to compare results to previously published data.Methods: Time-to-event analysis for mean treatment duration (estimated as the Restricted Mean Survival Time), b/tsDMARD failure, and b/tsDMARDs switching was performed for 230 patients (n = 147 RA, 46 PsA, 37 AS) who commenced their first b/tsDMARD between 2008 and 2018. Patients were managed in a dedicated “biologics” clinic in a tertiary hospital; the choice of b/tsDMARD was clinician driven based on medical factors and patient preferences. The effect of covariates on switching risk was analysed by a conditional risk-set Cox proportional-hazards model. Treatment retention data was compared to a historical analysis (2002–2008).Results: The proportions remaining on treatment (retention) were similar, throughout follow-up, for the first, second and third b/tsDMARDs across all patients (p = 0.46). When compared to RA patients, the risk of b/tsDMARD failure was halved in PsA patients [Hazard Ratio (HR) = 0.50], but no different in AS patients (HR = 1.0). The respective restricted mean (95%CI) treatment durations, estimated at 5 years of follow-up, were 3.1 (2.9, 3.4), 4.1 (3.7, 4.6), and 3.3 (2.8, 3.9) years, for RA, PsA, and AS, respectively. Age, gender, disease duration, smoking status and the use of concomitant csDMARDS were not associated with the risk of bDMARD failure. The most common reasons for switching in the first and subsequent years were secondary (n = 62) and primary (n = 35) failure. Comparison with historical data indicated no substantive differences in switching of the first biologic for RA and PsA.Conclusion: Similar retention rates of the second and third compared to the first b/tsDMARD in RA, PsA, and AS support a strategy of differential b/tsDMARDs use informed by patient presentation. Despite greater availability of b/tsDMARDs with differing mechanisms of action, retention rates of the first b/tsDMARD remain similar to previous years.

Bronchiectasis is as crucial as interstitial lung disease in the severe pneumonia that occurs during treatment with biologic DMARDs in rheumatoid arthritis: a retrospective cohort study in a single facility.

Interstitial lung disease (ILD) carries a risk for severe pneumonia in patients with rheumatoid arthritis (RA). Bronchiectasis, another risk of severe pneumonia, has not been well elucidated in RA. We investigated the types of respiratory diseases in RA and correlated them to severe pneumonia during the course of treatment using biologic DMARDs (bDMARDs), with special attention to bronchiectasis and ILD. RA patients were examined by computed tomography before starting bDMARDs and divided into three groups: normal, bronchiectasis and ILD. The log-rank test and Dunnett's multiple comparisons test were employed for the statistical analysis. Among 424 patients, 350 were categorized as normal, 32 as having bronchiectasis, and 42 as having ILD. Two in the normal group, three in the bronchiectasis group and four in the ILD group developed severe pneumonia. The log-rank test showed a significant difference among the three groups (p < 0.0001). The pneumonia-free rates in the bronchiectasis and ILD groups were significantly lower than the normal group, respectively, with Dunnett's multiple comparison test (p < 0.0001). This study suggests that the bronchiectasis that occurs in RA carries a risk of severe pneumonia during treatment with bDMARDs that is comparable to ILD.

Predictors of drug survival for biologic and targeted synthetic DMARDs in rheumatoid arthritis: Analysis from the TRA Clinical Electronic Registry

In this study we aimed to identify the predictors of drug survival for biologic and targeted synthetic DMARDs (bDMARDs and tsDMARDs) among patients with rheumatoid arthritis (RA) in a real-world setting. Data from RA patients receiving bDMARDs and tsDMARDs between 2007 and 2019 were extracted from the Taiwan Rheumatology Association Clinical Electronic Registry (TRACER). Patients were categorized into tumor necrosis factor-alpha (TNF-α) inhibitors, non-TNF-α inhibitors, and tofacitinib groups. The primary outcome was 3-year drug retention and the causes of bDMARDs and tsDMARDs discontinuation were recorded. Baseline demographic data before the initiation of bDMARDs and tsDMARDs treatment were analyzed to identify the predictors of 3-year drug survival. A total of 1,270 RA patients were recruited (TNF-α inhibitors: 584; non-TNF-α inhibitors: 535; tofacitinib: 151). The independent protective factors for 3-year drug survival were positive rheumatoid factor (RF) (HR: 0.48, 95% CI: 0.27-0.85, p = 0.013) and biologics-naïve RA (HR: 0.61, 95% CI: 0.39-0.94, p = 0.024). In contrast, positive anti-citrullinated protein antibody (ACPA) (HR: 2.24, 95% CI: 1.32-3.79, p = 0.003) and pre-existing latent tuberculosis (HR: 2.90, 95% CI: 2.06-4.09, p<0.001) were associated with drug discontinuation. RA patients treated with TNF-α inhibitors exhibited better drug retention, especially in the biologics-naïve subgroup (p = 0.037). TNF-α inhibitors were associated with lower cumulative incidence of discontinuation due to inefficacy and adverse events (both p<0.001). Baseline RF and ACPA positivity in abatacept-treated patients were associated with a better 3-year drug survival. However, negative ACPA levels predicted superior drug survival of TNF-α inhibitors and tofacitinib. In conclusion, bio-naïve status predicted better drug survival in TNF-α inhibitors-treated RA patients. RF and ACPA positivity predicted better abatacept drug survival. In contrast, ACPA negativity was associated with superior TNF-α inhibitors and tofacitinib survival.

The effectiveness and safety of Tripterygium wilfordii glycosides combined with disease-modifying anti-rheumatic drugs in the treatment of rheumatoid arthritis: A systematic review and meta-analysis of 40 randomized controlled trials.

This systematic review and meta-analysis were performed to investigate the efficacy and safety of Tripterygium wilfordii glycosides (TG) for rheumatoid arthritis (RA) from the current literature. An electronic search was conducted in eight databases (PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese VIP Database, and Wanfang Database) from inception until September 2020. Randomized controlled trials (RCTs) with risk of bias (RoB) score ≥ 4 according to the Cochrane RoB tool were included for the analyses. The primary outcome measures were duration of morning stiffness (DMS), tender joint count (TJC), swollen joint count (SJC), visual analog score (VAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF). The secondary outcome measures were the total clinical effective rate and adverse events. All the analyses were used by the random effects models. The meta-analysis was performed using RevMan 5.3 and STATA 14.0. A total of 40 RCTs with 3092 patients met our inclusion criteria. This meta-analysis showed that TG plus DMARDs for RA could decrease the DMS (p < .001), TJC (p < .001), SJC (p < .001), VAS (p < .001), serum CRP (p < .001), ESR (p < .001), and RF (p < .001) and improve total effective rate (p < .001). In addition, TG was generally safe and well tolerated in RA patients. Despite the limitations, the present evidence supports, at least to an extent, that TG can be recommended for routine use for RA patients. More large multicenter and high-quality RCTs are required for further research.

Clinico-genetic model to predict methotrexate intolerance in rheumatoid arthritis.

Methotrexate is the gold-standard DMARD in rheumatoid arthritis but is often associated with "mild" adverse effects like intolerance or laboratory abnormalities. Although non-life threatening, they are responsible for drug discontinuation in 17-50%. There is limited data on clinical and genetic markers that predict their occurrence. This prospective study enrolled patients with active rheumatoid arthritis. They were started on methotrexate at a weekly dose of 15mg, escalated gradually to reach 25mg which was continued till the end of the study. Intolerance (symptomatic adverse effects) was ascertained by a questionnaire at 4, 8, 16, and 24weeks. Laboratory testing for occurrence of cytopenia and/or transaminitis was done at the same study visits. Seven SNPs in four genes involved in methotrexate handling were genotyped using real-time polymerase chain reaction. This study included 110 patients with rheumatoid arthritis who received methotrexate for 24weeks; the final mean weekly methotrexate dose was 22.0 ± 4.0mg. Methotrexate intolerance occurred in 40 (37%), common being nausea (and vomiting) in 29 and anxiety (and dizziness) in 9. It was associated with lower BMI at baseline (21.5 ± 3.7, 23.8 ± 4.6kg/m2, p = 0.01). FPGS rs10106 was significantly associated with intolerance with an allelic odds ratio (95% CI) of 2.02 (1.14-3.57) and the recessive genetic model (AA+AG versus GG) with an odds ratio of 3.8 (95% CI 1.5-9.6, p = 0.004). A model including both BMI and FPGS rs10106 could modestly predict methotrexate intolerance with an accuracy of 66.3%. A clinical-genetic model including BMI and SNP FPGS 10101 was found to have a modest prediction ability for methotrexate intolerance.Key Points• Methotrexate intolerance (symptomatic adverse effects) was common and occurred in 37% patients over 6months.• SNP FPGS rs10106 and low body mass index were associated with methotrexate intolerance.• Clinico-genetic model had a modest ability of 66% for predicting intolerance.

Mechanism based pharmacodynamic interactions of glucocorticoids and DMARDs- A review

Combination of conventional disease-modifying antirheumatic drugs (cDMARDs), which assist in achieving effective disease control and functional outcomes in rheumatoid arthritis (RA), is widely accepted as an effective treatment regimen. Steroid is often used in combination with DMARDs and there are several uncertainties associated with the regimen, including the therapeutic benefits of the combination. Further understanding the pharmacodynamics and mechanism of actions of steroids, and possible drug interactions may assist in improving the treatment outcomes. While the treatment has shown to be effective with better outcome, the use of steroids in the combination regime has been a topic of contradiction. The pharmacodynamic actions of corticosteroids and cDMARDs is variable and overlapping in some domains. In a highly dynamic and constantly adopting immune system, the expression of receptors and signal pathways depends on various factors including the status of cytokine and antigen load. The pattern of introduction of the drugs is one of the major challenges that hampers the effective use of synergism and other interactions associated with the combination. Understanding the drug mechanism and interaction pathways and their variability is essential for customizing the treatment strategies. This review article addresses the current trends of combined treatment in the management of RA. It is also aimed at providing consolidated information on the pharmacodynamic interactions of glucocorticoids and DMARDs in RA.

Patients' Attitudes and Experiences of Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis and Spondyloarthritis: A Qualitative Synthesis.

ObjectiveNonadherence to disease‐modifying antirheumatic drugs (DMARDS) in rheumatoid arthritis (RA) and spondyloarthritis (SpA) results in increased disease activity and symptoms and poorer quality of life. We aimed to describe patients’ attitudes and experiences of DMARDs in RA and SpA to inform strategies to improve medication adherence.MethodsDatabases (MEDLINE, Embase, PsycINFO, and CINAHL) were searched to January 2016. Thematic synthesis was used to analyze the findings.ResultsFrom 56 studies involving 1,383 adult patients (RA [n = 1,149], SpA [n = 191], not specified [n = 43]), we identified 6 themes (with subthemes): intensifying disease identity (severity of sudden pharmacotherapy, signifying deteriorating health, daunting lifelong therapy), distressing uncertainties and consequences (poisoning the body, doubting efficacy, conflicting and confusing advice, prognostic uncertainty with changing treatment regimens), powerful social influences (swayed by others’ experiences, partnering with physicians, maintaining roles, confidence in comprehensive and ongoing care, valuing peer support), privilege and right of access to biologic agents (expensive medications must be better, right to receive a biologic agent, fearing dispossession), maintaining control (complete ownership of decision, taking extreme risks, minimizing lifestyle intrusion), and negotiating treatment expectations (miraculous recovery, mediocre benefit, reaching the end of the line).ConclusionPatients perceive DMARDs as strong medications with alarming side effects that intensify their disease identity. Trust and confidence in medical care, positive experiences with DMARDS among other patients, and an expectation that medications will help maintain participation in life can motivate patients to use DMARDs. Creating a supportive environment for patients to voice their concerns may improve treatment satisfaction, adherence, and health outcomes.

Gender Is a Risk Factor for Annual Decline in Estimated Glomerular Filtration Rate in Patients Treated with Biological DMARDs in Rheumatoid Arthritis and Ankylosing Spondylitis: a Retrospective Observational Study.

BackgroundThis study identified the risk factors of changes in renal function in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) treated with biological disease-modifying anti-rheumatic drugs (bDMARDs).MethodsWe retrospectively enrolled patients with RA (n = 293) and AS (n = 125) treated with bDMARDs. The estimated glomerular filter rate (eGFR) using the Modification of Diet in Renal Disease equation was applied for assessment of annual changes in renal function between initiation and last visit after bDMARD therapy. The annual change in eGFR was used as an indicator for change in renal function. Statistical significance was assessed by Mann-Whitney test, Spearman's correlation coefficient, and multivariate linear regression analysis.ResultsThe positive annual change in eGFR in women was significantly noted, compared to that in men (P = 0.004). The annual change in eGFR was different between men and women (P = 0.038) in RA, but not in AS patients (P = 0.126). In multivariate linear regression analysis, women patients and increased serum creatinine at baseline were closely associated with positive annual change in eGFR in both RA and AS patients. In RA patients, younger age and lower ESR level were considered risk factors of positive annual change in eGFR (P = 0.013 and P = 0.022, respectively). However, disease duration and duration of bDMARD use were not associated with annual change in eGFR.ConclusionThis study found that gender, especially men, might be responsible for annual decline in eGFR in RA and AS patients treated with bDMARDs.

Cancer risk with biologic DMARDs in rheumatoid arthritis

Cancer risk with biologic DMARDs in rheumatoid arthritis

Use of Non Biologic DMARD in Rheumatoid Arthritis with Emphasis on Leflunomide

Use of Non Biologic DMARD in Rheumatoid Arthritis with Emphasis on Leflunomide

Stopping tumour necrosis factor-targeted biological DMARDs in rheumatoid arthritis.

The combined use of MTX and biological DMARDs (bDMARDs) targeting TNF has revolutionized treatment of RA, and clinical remission becomes a realistic treatment goal. After sustained remission, discontinuation of bDMARDs without disease flare has been emerging as an important theme from the risk-benefit point of view and economic burden. According to several studies, approximately half of early RA patients could discontinue TNF-targeted bDMARDs without clinical flare and functional impairment after obtaining low disease activity or remission by treatment with bDMARDs and MTX. For established RA, however, fewer patients sustained remission or low disease activity after the discontinuation of bDMARDs, compared with early RA. The results were controversial among studies, and the percentage of patients who could successfully discontinue bDMARDs ranged from 13 to 48% at 1 year after discontinuation. From the adalimumab discontinuation without functional and radiographic damage progression following sustained remission study and the induction of remission by infliximab in RA study, deep remission at discontinuation was a key factor for maintaining the treatment holiday of bDMARDs in established RA patients. However, such early intensive treatment would have the potential for reducing drug-induced adverse effects and reducing long-term medical costs, although the risks of worsening clinical, structural and functional outcomes should be considered, with careful monitoring.

PMS94 - Impact of National Criteria and Healthcare System Characteristics on Access to Biologic Dmards in Rheumatoid Arthritis In Europe

PMS94 - Impact of National Criteria and Healthcare System Characteristics on Access to Biologic Dmards in Rheumatoid Arthritis In Europe

SAT0036 Retention of Tocilizumab Therapy: A Comparison between Tocilizumab in Monotherapy and in Combination with DMARDS Based on the Tocerra Collaboration

BackgroundClinical trials have shown that tocilizumab (TCZ) is efficacious as monotherapy and in combination with methotrexate (MTX) or other DMARDs. However, longitudinal TCZ retention data from large registry populations have...

THU0117 Methotrexate (MTX) Optimal Regimen: Dose Escalation to Least at 20Mg/W or 0.3Mg/Kg/W IF Remission is not Reached is the Key Factor to Get Favorable RA Outcomes at 1 and 2 Years. Results from the ESPOIR Cohort

BackgroundMTX is recommended as the first DMARD in rheumatoid arthritis. Despite its widespread use and more than two decades of experience, considerable variations exist among rheumatologists in prescribing MTX.ObjectivesTo describe...

Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis

ObjectivesTo update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism(EULAR) Task Force treatment recommendations.MethodsMedline,...

FRI0150 Maintenance of remission in rheumatoid arthritis patients with low-moderate disease activity following withdrawal of certolizumab PEGOL treatment: Week 52 results from the certain study

BackgroundCertolizumab pegol (CZP) increased rates of remission and low disease activity (LDA) as an addition to non-biologic DMARDs in rheumatoid arthritis (RA) patients (pts) with long-standing, low/moderate disease activity (DA).1ObjectivesTo...