The association between increased body mass index and response to conventional synthetic DMARD treatment in rheumatoid arthritis: Results from the METEOR database

Rheumatology ◽  
2021 ◽  
Author(s):  
Mrinalini Dey ◽  
Sizheng S Zhao ◽  
Robert J Moots ◽  
Sytske Anne Bergstra ◽  
Robert B Landewe ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Similar Response ◽  
Obese Patients ◽  
Eular Response ◽  
Early Ra ◽  
Dmard Treatment ◽  
Established Disease ◽  
Das28 Remission ◽  
Methotrexate Dose ◽  
Few Data

Abstract Background Few data exist on the association between increased BMI and response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in rheumatoid arthritis (RA). We aimed to explore the association between increased (overweight or obese) BMI on csDMARD-prescribing, methotrexate-dose and disease activity over 12-months. Methods Participants in an international RA database were stratified into early (<1year post-diagnosis) and established RA. EULAR response, DAS28 remission and treatments were recorded at baseline, 6-months and 12-months. Increased BMI was explored in early and established RA, as predictors of good EULAR response, DAS28 remission, number of csDMARDs and methotrexate-dose, using logistic and linear regression. Results Data from 1313 patients, 44.3% with early RA, were examined. In early RA, increased BMI was not significantly associated with remission. In established RA, obese patients on monotherapy were significantly less likely to achieve good EULAR response or DAS28 remission at 6 months and more likely to be treated with combination csDMARDs, compared with normal BMI. In patients taking methotrexate, overweight and obese patients with early and established RA were exposed to higher methotrexate doses (mono- and combination-therapy), with a mean dose of 20mg/week, compared to 15mg/week in those of normal BMI. Conclusion We observed, compared to patients with normal BMI, overweight and obese individuals experienced more intensive csDMARD exposures. Similar response rates were observed in early RA but increased BMI was associated with reduced response in established RA. Optimisation of targeted RA treatment remains important, particularly in those with increased BMI where response in established disease may be attenuated.

scholarly journals P62 Assessing the effect of increased body mass on response to DMARD treatment in rheumatoid arthritis: results from the METEOR database

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Mrinalini Dey ◽  
Sizheng S Zhao ◽  
Eftychia-Eirini Psarelli ◽  
Robert J Moots ◽  
Robert Landewe ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Body Mass ◽  
Normal Weight ◽  
Sensitivity Analyses ◽  
Tender Joint Count ◽  
Weekly Dose ◽  
Obese Patients ◽  
Eular Response ◽  
Significant Difference ◽  
Das28 Remission

Abstract Background Worldwide, >60% patients with rheumatoid arthritis (RA) are overweight/obese (body mass index, BMI≥25kg/m2). Studies demonstrate poorer disease outcomes and health-related quality of life in these patients. However, little is known about the effect of increased BMI on drug choice, dosing, or treatment response. Objective: To explore the effect of increased BMI on DMARD-prescribing, methotrexate (MTX)-dose, and disease activity over 12 months. Methods Participants registered on METEOR (international database of RA patients) were stratified into early (<1year post-diagnosis, eRA), and established RA (estRA). EULAR response and DAS28 remission (including components), and treatment regimens were recorded at baseline, 6, and 12 months. Increased BMI (defined overweight and obese) were explored in 1) eRA and 2) estRA, as predictors of good EULAR response, DAS28 remission, number of DMARDs prescribed, and MTX-dose. Logistic and linear regression models (controlling for age, gender, smoking, and baseline outcome values), subgroup analyses (by drug exposure), and sensitivity analyses, were performed. Results 1,313 patients (1056 female) were included, 582 eRA. In eRA, increased BMI was not significantly associated with remission outcomes. In estRA, obese patients on monotherapy were statistically significantly less likely to achieve good EULAR response [OR 0.4 (95%CI 0.23-0.7)] or DAS28 remission [OR 0.47 (95%CI 0.24-0.88)] at 6 months, compared to those of normal weight. A similar trend observed at 12 months did not reach significance. Obese estRA patients were more likely to be treated with combination conventional synthetic DMARDs (csDMARD) than monotherapy, compared with those of normal weight, significant at 6 months [OR 1.59 (95%CI 1.03-2.45)]. In early and established disease, no significant difference in remission outcomes was demonstrated for combination compared to monotherapy. However, overweight/obese individuals were less likely to achieve remission overall (non-significant). Regarding components of remission, tender joint count and ESR in estRA were higher in overweight/obese individuals at 6 months [β 1.05 (95%CI 0.05-2.06)] and 12 months [β 6.58 (95%CI 0.16-12.99)] respectively, compared to those of normal weight. Sensitivity analyses showed no difference in the above results. MTX-dose was available for 613 patients at sequential visits. Within this subgroup, overweight/obese patients with both eRA and estRA were exposed to higher doses of MTX (mono- and combination-therapy) at any time-point, compared to those of normal weight. eRA: overweight: β 5.33, 95%CI 3.10-7.56; obese: β 6.01, 95%CI 3.57-8.46. estRA: overweight: β 4.87, 95%CI 3.79-5.95; obese: β 2.69, 95%CI 1.56-3.83. An average weekly dose of 20mg was prescribed in overweight/obese patients, compared to 15mg in those of normal weight. Conclusion We observed that overweight/obese individuals require more intense csDMARD therapy to achieve the same treatment targets as those of normal weight. Awareness of this is particularly important given the increasing obesity prevalence in RA. Disclosures M. Dey None. S.S. Zhao None. E. Psarelli None. R.J. Moots None. R. Landewe Other; Member of METEOR board. N.J. Goodson None.

scholarly journals OP0220 ASSESSING THE EFFECT OF INCREASED BODY MASS INDEX ON RESPONSE TO TNF INHIBITORS IN ESTABLISHED RHEUMATOID ARTHRITIS: RESULTS FROM THE METEOR DATABASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 137.1-137
Author(s):  
M. Dey ◽  
S. S. Zhao ◽  
R. J. Moots ◽  
R. B. M. Landewé ◽  
N. Goodson
Keyword(s):  
Rheumatoid Arthritis ◽  
Body Mass Index ◽  
Body Mass ◽  
Personalised Medicine ◽  
Normal Weight ◽  
Sensitivity Analyses ◽  
Established Rheumatoid Arthritis ◽  
Eular Response ◽  
Significant Difference ◽  
Das28 Remission

Background:Rheumatoid arthritis (RA) is associated with increased body mass index (BMI)- 60% of patients are either overweight or obese. Obesity in RA has been shown to predict reduced response to biologic therapy including tumour-necrosis-factor inhibitors (TNFi) [1]. However, it is not clear whether increased BMI influences response to all TNFi drugs in RA.Objectives:1.To explore whether BMI is associated with response to TNFi in patients with established rheumatoid arthritis (estRA), including those newly-starting on these drugs.Methods:Participants with estRA (>1year since diagnosis) taking biologic medications, registered on METEOR (international database of RA patients), 2008-2013, were included. EULAR response, DAS28 remission (including components), and treatment regimens were recorded at baseline, 6, and 12 months. WHO definitions of overweight (BMI≥ 25) and obese (BMI≥30) were explored as predictors of TNFi response (good EULAR response and DAS28 remission) using normal BMI as comparator. Logistic and linear regression models (controlling for age, gender, smoking, and baseline outcomes) and sensitivity analyses were performed. Subgroup analyses were performed for grouped TNFi and individual TNFi (infliximab, IFX; adalimumab, ADA; etanercept, ETN).Results:247 patients with estRA were taking a biologic at 6 months, and 231 patients were taking a biologic at 12 months. Obese patients taking any biologic were significantly less likely to achieve DAS28 remission (OR 0.33 [95%CI 0.12-0.80]) or good EULAR response (OR 0.37 [95%CI 0.16-0.81]) after 6 months, compared to those of normal BMI; this was also demonstrated in those co-prescribed methotrexate (DAS28 remission: OR 0.23 [95%CI 0.07-0.62]; good EULAR response: OR 0.39 [95%CI 0.15-0.92]). These associations did not remain statistically significant at the 12 months assessment.Regarding specific anti-TNF therapies, RA patients treated with monoclonal antibody (-mab) TNFis (IFX/ADA/ GOL) were significantly less likely to achieve good EULAR response at 6 months if they were obese RA (n=38), compared to those of normal weight (n=44) (OR 0.17 [95%CI 0.03-0.59]). A similar non-significant difference was demonstrated for DAS28 remission, and 12-month remission. Specifically, obese individuals were significantly less likely to achieve good EULAR response at 6 months with IFX (OR 0.09 [95%CI 0.00-0.61]; n=20), and significantly less likely to achieve DAS28 remission at 6 months when newly-starting ADA (OR 0.14 [95%CI 0.01-0.96]; n=17), compared to those of normal weight. There were no significant differences in remission outcomes between individuals of different BMI taking ETN. A small number of individuals stopped taking their respective biologic after 6months; reason for cessation was not recorded.Similar outcomes were seen in patients already established on anti-TNF therapy, with overweight and obese individuals less likely overall to be in DAS28 remission at all time points.Conclusion:In established RA, obesity is associated with reduced treatment response to -mab TNFi. No association between increased BMI and response to ETA was observed. Using BMI to direct biologic drug choice could prove to be a simple and cost-effective personalised-medicine approach to prescribing.References:[1]Schäfer M, Meißner Y, Kekow J, Berger S, Remstedt S, Manger B, et al. Obesity reduces the real-world effectiveness of cytokine-targeted but not cell-targeted disease-modifying agents in rheumatoid arthritis. Rheumatology. 2019 Nov 20.Disclosure of Interests:Mrinalini Dey: None declared, Sizheng Steven Zhao: None declared, Robert J Moots: None declared, Robert B.M. Landewé Consultant of: AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Co.; Galapagos NV; Novartis; Pfizer; UCB Pharma, Nicola Goodson: None declared

scholarly journals FRI0046 PHARMACOGENOMICS-DRIVEN INDIVIDUALIZED PREDICTION OF TREATMENT RESPONSE TO METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS: A MACHINE LEARNING APPROACH

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 598.2-598
Author(s):  
E. Myasoedova ◽  
A. Athreya ◽  
C. S. Crowson ◽  
R. Weinshilboum ◽  
L. Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Machine Learning ◽  
Supervised Machine Learning ◽  
Research Support ◽  
Eular Response ◽  
Learning Methods ◽  
Machine Learning Methods ◽  
Early Ra ◽  
Genome Wide

Background:Methotrexate (MTX) is the most common anchor drug for rheumatoid arthritis (RA), but the risk of missing the opportunity for early effective treatment with alternative medications is substantial given the delayed onset of MTX action and 30-40% inadequate response rate. There is a compelling need to accurately predicting MTX response prior to treatment initiation, which allows for effectively identifying patients at RA onset who are likely to respond to MTX.Objectives:To test the ability of machine learning approaches with clinical and genomic biomarkers to predict MTX response with replications in independent samples.Methods:Age, sex, clinical, serological and genome-wide association study (GWAS) data on patients with early RA of European ancestry from 647 patients (336 recruited in United Kingdom [UK]; 307 recruited across Europe; 70% female; 72% rheumatoid factor [RF] positive; mean age 54 years; mean baseline Disease Activity Score with 28-joint count [DAS28] 5.65) of the PhArmacogenetics of Methotrexate in RA (PAMERA) consortium was used in this study. The genomics data comprised 160 genome-wide significant single nucleotide polymorphisms (SNPs) with p<1×10-5 associated with risk of RA and MTX metabolism. DAS28 score was available at baseline and 3-month follow-up visit. Response to MTX monotherapy at the dose of ≥15 mg/week was defined as good or moderate by the EULAR response criteria at 3 months’ follow up visit. Supervised machine-learning methods were trained with 5-repeats and 10-fold cross-validation using data from PAMERA’s 336 UK patients. Class imbalance (higher % of MTX responders) in training was accounted by using simulated minority oversampling technique. Prediction performance was validated in PAMERA’s 307 European patients (not used in training).Results:Age, sex, RF positivity and baseline DAS28 data predicted MTX response with 58% accuracy of UK and European patients (p = 0.7). However, supervised machine-learning methods that combined demographics, RF positivity, baseline DAS28 and genomic SNPs predicted EULAR response at 3 months with area under the receiver operating curve (AUC) of 0.83 (p = 0.051) in UK patients, and achieved prediction accuracies (fraction of correctly predicted outcomes) of 76.2% (p = 0.054) in the European patients, with sensitivity of 72% and specificity of 77%. The addition of genomic data improved the predictive accuracies of MTX response by 19% and achieved cross-site replication. Baseline DAS28 scores and following SNPs rs12446816, rs13385025, rs113798271, and rs2372536 were among the top predictors of MTX response.Conclusion:Pharmacogenomic biomarkers combined with DAS28 scores predicted MTX response in patients with early RA more reliably than using demographics and DAS28 scores alone. Using pharmacogenomics biomarkers for identification of MTX responders at early stages of RA may help to guide effective RA treatment choices, including timely escalation of RA therapies. Further studies on personalized prediction of response to MTX and other anti-rheumatic treatments are warranted to optimize control of RA disease and improve outcomes in patients with RA.Disclosure of Interests:Elena Myasoedova: None declared, Arjun Athreya: None declared, Cynthia S. Crowson Grant/research support from: Pfizer research grant, Richard Weinshilboum Shareholder of: co-founder and stockholder in OneOme, Liewei Wang: None declared, Eric Matteson Grant/research support from: Pfizer, Consultant of: Boehringer Ingelheim, Gilead, TympoBio, Arena Pharmaceuticals, Speakers bureau: Simply Speaking

Patterns of Magnetic Resonance Imaging Bone Erosion in Rheumatoid Arthritis — Which Bones Are Most Frequently Involved and Show the Most Change?: Figure 1.

2011 ◽  
Vol 38 (9) ◽  
pp. 2014-2017 ◽  
Author(s):  
MIKKEL ØSTERGAARD ◽  
UFFE MØLLER DØHN ◽  
ANNE DUER-JENSEN ◽  
MERETE LUND HETLAND ◽  
KIM HØRSLEV-PETERSEN ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Disease Duration ◽  
Bone Erosion ◽  
Resonance Imaging ◽  
Early Ra ◽  
Established Disease ◽  
Magnetic Resonance Imaging Mri ◽  
Erosive Progression

Objective.To investigate by magnetic resonance imaging (MRI) which bones in wrists and metacarpophalangeal (MCP) joints most frequently show bone erosions, and which most frequently demonstrate erosive progression, in early and established rheumatoid arthritis (RA).Methods.MRI datasets from 258 RA patients [126 with early RA (disease duration < 6 months)] were analyzed, of whom 223, including 126 with early RA, had 1-year followup MRI. All patients had MRI of one wrist, whereas 86 patients had additional images of 2nd–5th MCP joints, and 46 patients additional images of the contralateral wrist. MRI were evaluated blinded by one reader, according to the OMERACT RA MRI scoring system (RAMRIS) for erosions, and presence/absence of erosions was noted in each bone, as was presence/absence of erosive progression.Results.The capitate, ulna, lunate, triquetrum, and scaphoid were the 5 bones with both most frequent baseline erosions and most frequently demonstrated erosive progression. No bones were without erosions. Patterns of erosions and progression were similar in early and established RA. No major difference between dominant and nondominant wrists was detected. In the fingers, the 2nd–3rd MCP joint most frequently displayed erosions and erosive progression.Conclusion.The distribution and frequency of bone erosion and erosive progression as detected by MRI in RA wrists and MCP joints were identified. No pattern differences between early versus established disease and dominant versus nondominant sides were detected. No bones showed erosive progression. Thus, no self-evident simplification of the RAMRIS erosion score was identified. Bone involvement patterns may be considered, when joints are selected for MRI protocols for clinical trials and practice.

scholarly journals Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early stage of rheumatoid arthritis

2015 ◽  
Vol 75 (4) ◽  
pp. 763-771 ◽  
Author(s):  
L Yeo ◽  
N Adlard ◽  
M Biehl ◽  
M Juarez ◽  
T Smallie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Stage ◽  
Symptom Duration ◽  
Mrna Levels ◽  
Tissue Sections ◽  
Early Ra ◽  
Machine Learning Approach ◽  
Established Disease ◽  
Very Early Ra ◽  
Von Willebrand

Background and objectivesFor our understanding of the pathogenesis of rheumatoid arthritis (RA), it is important to elucidate the mechanisms underlying early stages of synovitis. Here, synovial cytokine production was investigated in patients with very early arthritis.MethodsSynovial biopsies were obtained from patients with at least one clinically swollen joint within 12 weeks of symptom onset. At an 18-month follow-up visit, patients who went on to develop RA, or whose arthritis spontaneously resolved, were identified. Biopsies were also obtained from patients with RA with longer symptom duration (>12 weeks) and individuals with no clinically apparent inflammation. Synovial mRNA expression of 117 cytokines was quantified using PCR techniques and analysed using standard and novel methods of data analysis. Synovial tissue sections were stained for CXCL4, CXCL7, CD41, CD68 and von Willebrand factor.ResultsA machine learning approach identified expression of mRNA for CXCL4 and CXCL7 as potentially important in the classification of early RA versus resolving arthritis. mRNA levels for these chemokines were significantly elevated in patients with early RA compared with uninflamed controls. Significantly increased CXCL4 and CXCL7 protein expression was observed in patients with early RA compared with those with resolving arthritis or longer established disease. CXCL4 and CXCL7 co-localised with blood vessels, platelets and CD68+macrophages. Extravascular CXCL7 expression was significantly higher in patients with very early RA compared with longer duration RA or resolving arthritisConclusionsTaken together, these observations suggest a transient increase in synovial CXCL4 and CXCL7 levels in early RA.

scholarly journals Higher levels of anti-phosphorylcholine autoantibodies in early rheumatoid arthritis indicate lower risk of incident cardiovascular events

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Sofia Ajeganova ◽  
Maria L. E. Andersson ◽  
Johan Frostegård ◽  
Ingiäld Hafström
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Events ◽  
Proportional Hazards ◽  
Coronary Intervention ◽  
Cox Proportional Hazards ◽  
Protective Effects ◽  
Early Ra ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Das28 Remission

Abstract Background The increased risk of cardiovascular events (CVE) in rheumatoid arthritis (RA) is not fully explained by traditional risk factors. Immuno-inflammatory mechanisms and autoantibodies could be involved in the pathogenesis of atherosclerotic disease. It has been suggested that anti-phosphorylcholine antibodies (anti-PC) of the IgM subclass may have atheroprotective effects. Here, we aimed to investigate the association between levels of IgM anti-PC antibodies with CVE in patients with early RA. Methods The study population was derived from the BARFOT early RA cohort, recruited in 1994–1999. The outcome of incident CVE (AMI, angina pectoris, coronary intervention, ischemic stroke, TIA) was tracked through the Swedish Hospital Discharge and the National Cause of Death Registries. Sera collected at inclusion and the 2-year visit were analyzed with ELISA to determine levels of anti-PC IgM. The Kaplan-Meier estimates and Cox proportional hazards regression models were used to compare CV outcome in the groups categorized by baseline median level of IgM anti-PC. Results In all, 653 patients with early RA, 68% women, mean (SD) age 54.8 (14.7) years, DAS28 5.2 (1.3), 68% seropositive, and without prevalent CVD, were included. During the follow-up of mean 11.7 years, 141 incident CVE were recorded. Baseline IgM anti-PC above median was associated with a reduction in risk of incident CVE in patients aged below 55 years at inclusion, HR 0.360 (95% CI, 0.142–0.916); in males, HR 0.558 (0.325–0.958); in patients with BMI above 30 kg/m2, HR 0.235 (0.065–0.842); and in those who did not achieve DAS28 remission at 1 year, HR 0.592 (0.379–0.924). The pattern of associations was confirmed in the models with AUC IgM anti-PC over 2 years. Conclusion Protective effects of higher levels of innate IgM anti-PC autoantibodies on CVE were detected in younger patients with RA and those at high risk of CVE: males, presence of obesity, and non-remission at 1 year.

scholarly journals The Effect of Socioeconomic Class and Immigrant Status on Disease Activity in Rheumatoid Arthritis: Data from BARFOT, a Multi-Centre Study of Early RA

2013 ◽  
Vol 7 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Maria L.E. Andersson ◽  
Stefan Bergman ◽  
Maria K. Söderlin
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Tender Joint Count ◽  
Immigrant Status ◽  
Tender Joint ◽  
Eular Response ◽  
Multi Centre Study ◽  
Socioeconomic Class ◽  
Early Ra

Background:There have been no reports on the effect of immigrant status and socioeconomic status on outcome in rheumatoid arthritis (RA) in Sweden.Methods:Between 1992 and 2006, 2,800 patients were included in the BARFOT study on early RA in Sweden. Disease Activity Score 28 joints (DAS28), Health Assessment Questionnaire (HAQ), treatment and European League Against Rheumatism (EULAR) response criteria were registered. In 2010, 1,430 patients completed a questionnaire enquiring about demographics and lifestyle factors.Results:One hundred and thirty-nine of the 1,430 patients (9.7%) were immigrants. At baseline immigrants had higher mean HAQ (1.2 vs 0.97 for non-immigrants, p=0.001), DAS28 (5.6 vs 5.2, p=0.000), visual analog scale (VAS) pain (56 mm vs 45 mm, p=0.000), VAS global health (53 mm vs 44 mm, p=0.000) and tender joint count (TJC) (10 vs 8, p=0.000). These differences persisted for up to 2 years of follow-up (for HAQ, for up to 8 years of follow-up). Immigrant status did not have any effect on swollen joint count (SJC), ESR, CRP or EULAR response. Socioeconomic class did not have any effect on treatment or outcome.Conclusions:Immigrants scored worse in pain, function and TJC for up to 2 years of follow-up, but they did not differ from non-immigrants in objective measures of inflammation or EULAR outcome. This could be due to different perceptions of health and pain and/or the stress of immigration. Socioeconomic class had no effect on treatment or outcome, and this could be due to the relatively egalitarian society in Sweden.

scholarly journals OP0098 POLYPHARMACY IS ASSOCIATED WITH A POORER TREATMENT RESPONSE AND INCREASED RISK OF ADVERSE EVENTS IN EARLY RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 54.1-54
Author(s):  
S. Benamar ◽  
C. Lukas ◽  
C. Daien ◽  
C. Gaujoux-Viala ◽  
L. Gossec ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Treatment Response ◽  
Univariate Analysis ◽  
Group Versus ◽  
Biological Database ◽  
Lower Probability ◽  
Research Support ◽  
Early Ra ◽  
Increased Risk

Background:Polypharmacy is steadily increasing in patients with rheumatoid arthritis (RA). They may interfere with treatment response and the occurrence of serious adverse events. Medications taken by a patient may reflect active comorbidities, whereas comorbidity indices usually used include past or current diseases.Objectives:To evaluate whether polypharmarcy is associated with treatment response and adverse events in an early RA cohort and to establish whether polypharmacy could represent a substitute of comorbidities.Methods:We used data from the French cohort ESPOIR, including 813 patients with early onset arthritis. Patients included the current study had to start their first disease modifying anti-rheumatic drug (DMARD) within 24 months of inclusion in the cohort. Disease activity data were collected at one, five and ten years from the initiation of the first DMARD. For each patient, treatments were collected at baseline and at five years. Medications count included all specialties other than background RA therapy, analgesics/NSAIDs and topicals. Polypharmacy was defined as a categorical variable based on the median and tertiles of distribution in the cohort. Treatment response was assessed by achieving DAS28 ESR remission (REM) at 1 year, 5 years and 10 years from the initiation of the first DMARD. The occurrence of severe adverse events (SAE) was measured by the occurrence of severe infection, hospitalization, or death during the 10-year follow-up. The association between patient’s characteristics and achievement of REM and occurrence of SAE were tested in univariate analysis. A logistic regression model was used to evaluate associations between polypharmacy and REM at 1 year, 5 years and 10 years (we used baseline polypharmacy for the 1-year analysis and five years polypharmacy for the 5- and 10-years analyses). Multivariate adjustment was made for age, sex, BMI, duration of disease, initial DAS28 ESR, initial HAQ, smoking status, rheumatic disease comorbidity index (RDCI).Results:The proportion of patients who achieved REM one year after the initiation of the first DMARD was 32.1% in the polypharmacy according to the median group (patients taken ≥2 medication) versus 67.9% in the non-polypharmacy group (p=0.07). At 5 years after the first DMARD, the proportion of patients with REM was 45.0% in the polypharmacy group versus 56.3% in the non-polypharmacy group (p=0.03). At 10 years the proportion of patients with REM was 32.5% in the polypharmacy group versus 67.5% (p=0.06). Patients who take greater or equal to 2 medications had a 40% lower probability of achieving REM (OR = 0.60 [0.38-0.94] p = 0.03) at 5 years from the first DMARD (if RDCI index was not included in the model). At 10 years, patients receiving multiple medications had a 43% lower probability of achieving REM (OR = 0.57 [0.34-0.94] p = 0.02). SAE incidence was 61 per 1000 patient-years. For patients who developed SAE all causes 71.4% where in the polypharmacy group versus 57.8% were in the non-polypharmacy group (p = 0.03; univariate analysis). These results are no longer significant after adjustment for comorbidities indices.Conclusion:In this early RA cohort, polypharmacy is associated with a poorer treatment response and increased risk of adverse events. Polypharmacy may represent a good substitute of comorbidities for epidemiological studies.Acknowledgements:We are grateful to Nathalie Rincheval (Montpellier) who did expert monitoring and data management and all theinvestigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine; MC. Boissier, Paris-Bobigny; A. Cantagrel, Toulouse; B. Combe, Montpellier; M. Dougados, Paris-Cochin; P. Fardellone and P. Boumier, Amiens; B. Fautrel, Paris-La Pitié; RM. Flipo, Lille; Ph. Goupille, Tours; F. Liote, Paris- Lariboisière; O. Vittecoq, Rouen; X. Mariette, Paris-Bicêtre; P. Dieude, Paris Bichat; A. Saraux, Brest; T. Schaeverbeke, Bordeaux; and J. Sibilia, Strasbourg).The work reported on in the manuscript did not benefit from any financial support. The ESPOIR cohort is sponsored by the French Society for Rheumatology. An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. Pfizer, Abbvie, Lilly and more recently Fresenius and Biogen also supported the ESPOIR cohort.Disclosure of Interests:Soraya Benamar: None declared, Cédric Lukas Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Consultant of: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Pfizer, Novartis and Roche-Chugai, Claire Daien Speakers bureau: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Consultant of: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Cécile Gaujoux-Viala Speakers bureau: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Consultant of: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Grant/research support from: Pfizer, Laure Gossec Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Anne-Christine Rat Speakers bureau: Pfizer, Lilly, Consultant of: Pfizer, Lilly, Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Grant/research support from: Novartis, Pfizer, and Roche-Chugai., Jacques Morel Speakers bureau: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Consultant of: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Grant/research support from: BMS, Pfizer

scholarly journals FRI0072 DISCONTINUATION OF DMARD USE IN RHEUMATOID ARTHRITIS PATIENTS WITH LUNG DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 612.1-613
Author(s):  
S. Pedro ◽  
T. Mikuls ◽  
J. Zhuo ◽  
K. Michaud
Keyword(s):  
Rheumatoid Arthritis ◽  
Lung Disease ◽  
Pulmonary Disease ◽  
Treatment Patterns ◽  
Dmard Treatment ◽  
Increased Risk ◽  
Pulmonary Manifestations ◽  
Clinical Models ◽  
Comorbidity Index ◽  
Time Varying Covariates

Background:Pulmonary manifestations such as interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD) are frequent extra-articular features that carry a poor prognosis in Rheumatoid Arthritis (RA). Little data is available on how RA patients (pts) with pulmonary disease are managed in real-world settings.Objectives:To assess treatment patterns and DMARD discontinuation in RA patients with comorbid lung disease in comparison with other RA patients.Methods:The study included RA Patients enrolled in the Forward Databank with ≥1 year observation after 2000 initiating a DMARD. Forward is a large longitudinal rheumatic disease registry in the US. RA patients’ diagnoses were rheumatologist-confirmed, and every 6 months participants completed comprehensive questionnaires regarding symptoms, disease outcomes, medications, and clinical events. Lung disease (LD+) was defined as at least one of the following: emphysema, asthma, bronchitis, COPD, pleural effusion, fibrosis of the lung, “RA lung”, or ILD, the later classified by ICD9 codes (England 2019). DMARDs were categorized hierarchically into four groups: csDMARDs, TNFi and NTNFi (bDMARDs), and tsDMARDs. Percentage of patients who initiated different DMARDs were reported for pts with LD+/LD-. Discontinuation was analyzed by Kaplan Meier (KM) curves, log-ranks tests, and Cox regression models using time-varying covariates. Best models were created using backward selection models (10% probability of removal) and pre-defined clinical models.Results:Of the 21,525 eligible RA patients, 13.8% had LD+ at the time they initiated a DMARD (follow-up: 69,597 pt-yrs (median 1.9 yrs/pt)). LD+ patients tended to have more severe RA outcomes and comorbidities. MTX-monotherapy (48% vs 44%, p<0.001) and NTNFi were initiated more frequently in LD+ pts with lower use of TNFi (Figure). DMARD discontinuation rates were higher among LD+ patients for all DMARD groups, but KM curves were only significantly different for csDMARDs and TNFi. Different HRs for LD+ were found depending on the model used ranging from 1.18 to 1.28, and all models revealed an increased risk of discontinuation for LD+ patients. Compared to csDMARDs, TNFi were more often discontinued (Table). Other variables associated with an increased risk of discontinuation included: HAQ, Rheumatoid Disease (RD) comorbidity index, pain, prior bDMARDs, and csDMARDs.Conclusion:Different DMARD treatment patterns were found for LD+ patients, who tended to initiate more csDMARD and NTNFi and less likely to initiate a TNFi. LD+ patients were at a higher risk of discontinuation irrespectively of the DMARD treatment, but with greater risk for TNF users.References:[1]England BR, et al. Arth Care Res. doi:10.1002/acr.24043.Figure.DMARD treatment initiators by disease groupTable .Cox models for DMARD discontinuation by stepwise (removal probability 10%) and clinical models including DMARD treatment.Model of DMARD persistence*Model 1- Stepwise-Without drugsModel 2 – StepwiseModel 3 - ClinicalLD+ vs LD–1.181.281.20(1.08 - 1.29)(1.13 - 1.45)(1.08 - 1.34)TNF vs csDmard1.321.22(1.08 - 1.63)(1.04 - 1.44)NTNF vs csDmard1.131.13(0.83 - 1.52)(0.90 - 1.41)tsDmard vs csDmard1.301.02(0.65 - 2.60)(0.64 - 1.62)*Best models searched/Clinical adjusted for LD+/LD-, DMARDs, age, sex, education, HAQ disability, RD comorbidity index, smoking, pain, glucocorticoids, year of entry, prior bDMARDs and csDMARDs counts and MRC breath scale.Disclosure of Interests:Sofia Pedro: None declared, Ted Mikuls Grant/research support from: Horizon Therapeutics, BMS, Consultant of: Pfizer, Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Kaleb Michaud: None declared

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