Biologics In Rheumatoid Arthritis Genetics And Genomics Study Syndicate Research Articles

OA40 Clinical and psychological factors associated with adherence based on a patient self-reported questionnaire: results from the biologics in rheumatoid arthritis genetics and genomics study syndicate (BRAGGS) cohort

Abstract Background/Aims To explore the relationship of clinical and psychological factors with adherence based on a patient self-reported questionnaire from a prospective longitudinal study of patients receiving TNFi biologic treatment for rheumatoid arthritis, recruited since 2008. Methods Analysis of data collected from a prospective longitudinal UK study (Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate [BRAGGSS]) of patients with moderate to severe RA commencing TNFi biologic treatment. Clinical data including Disease Activity Score-28 (DAS28), serological status (Rheumatoid Factor positivity) and body mass index (BMI) were collected. Patients also completed self-reported questionnaires, the health assessment questionnaire (HAQ), hospital anxiety and depression scale (HAD), beliefs about medicine questionnaire (BMQ), brief illness perception score (B-IPQ) and a self-reported adherence questionnaire. Adherence was defined as any deviation from prescribed medication regime such as altering the dose, forgetting a dose, stopping treatment, missing a dose, and taking less than instructed. Associations between demographic and psychological variables and adherence were evaluated using regression models and a multivariable logistic regression model was used to further evaluate associations, controlling for BMI. Results 1,513 patients (75.7% female, age 58.1 [IQR 16.0], disease duration 9.6 ± 9.6 years and pre-treatment DAS28 scores 5.7 ± 0.8) were included. 70% of patients self-reported adherence to their medication. When comparing the different TNFi treatments, etanercept had the lowest levels of adherence at the 3 and 6 month time-points. Adherence was higher in those with older age (β = 0.03, p< 0.01), higher baseline CRP levels (β = 0.01, p= 0.03) and higher necessity beliefs (β = 0.04, p= 0.03). Adherence was lower in those with higher tender joint counts at baseline (β=-0.03, p= 0.04) and 3 months (β = 0.03, p= 0.02) (Table I). These associations persisted after controlling for the effects of BMI using a multivariable logistic model. Conclusion Self-reported adherence was 70% in this BRAGGS population. Factors associated with non-adherence included higher tender joint counts and lower necessity beliefs pre-treatment, which may allow targeting of interventions to optimise adherence in these groups. Disclosure T.K.Y. Chong: None. N. Nair: None. A.W. Morgan: None. J.D. Isaacs: None. A.G. Wilson: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; K.H has grants from BMS and Pfizer. D. Plant: None. A. Barton: Grants/research support; A.B has received funding/speaker fees from BMS, Pfizer and Galapagos.

OA16 Therapeutic certolizumab pegol drug levels to achieve good EULAR response in patients with rheumatoid arthritis: results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS) cohort

Abstract Background/Aims Rheumatoid arthritis (RA) is a systemic inflammatory disease which is often treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) like tumour-necrosis factor inhibitors (TNFi) including certolizumab pegol (CTZ). A proportion of patients (approximately 30%) do not respond to treatment, and previous studies have shown that low drug levels and poor adherence are associated with poor response; however, an optimal drug level has not been defined or applied in clinical practice. The aim of this analysis is to determine an optimal CTZ drug level associated with a “good” European Alliance of Associations for Rheumatology (EULAR) response in fully adherent and non-adherent patients with RA. Methods In a prospective observational cohort study, patients with RA were treated with CTZ. At baseline, and at 6 months, 4-component DAS28 scores, as well as self-reported treatment adherence data were collected. Drug levels were measured using ELISA during follow-up at 6 months from treatment initiation. Patients were considered fully adherent if they self-reported never having altered, forgotten or omitted any dose of their biologic drug at follow-up. Patients without drug levels were excluded. In fully adherent patients, the relationship between random CTZ levels and clinical efficacy after 6 months was determined using a concentration-effect curve, and a receiver-operator characteristics (ROC) curve established a therapeutic cut-off concentration using the EULAR response classification. Median drug levels in “good” EULAR responders were compared between adherent and non-adherent patients to provide an estimated therapeutic range. Results Of 347 RA patients taking CTZ recruited, 111 (32.0%) had drug levels and EULAR response measured at 6 months, of which 42 (37.8%) also provided self-reported treatment adherence data. Of those, 37 (88.1%) reported being fully adherent. In 37 fully adherent RA patients taking CTZ, clinical efficacy was positively correlated with increasing CTZ concentration reaching a maximum median DAS28CRP improvement of 2.99 (IQR 2.67-3.40) with levels above 30mg/L. Levels exceeding 30mg/L showed no significant additional benefit. The ROC curve showed an area under the curve (AUC) of 0.714 (95% CI 0.526-0.901) for random CTZ levels with EULAR good response versus non/moderate responders. A cut-off of 30mg/L had a sensitivity and specificity of 86.4% and 60.0%, respectively, to classify good responders in fully adherent patients. Fully adherent good responders (n = 37) had a median drug level of 34.5mg/L (IQR 31-38), whereas good responders in the remaining cohort (n = 76) had a median drug level of 23.5 (IQR 15-30). Conclusion In RA patients taking CTZ, random drug levels were higher in EULAR good responders, and in fully adherent patients. A target lower threshold drug level cut-off of 30mg/L or a target range from 23.5mg/L to 34.5mg/L may be useful in clinical practice. Disclosure R.M. Hum: None. P. Ho: None. N. Nair: None. D. Plant: None. A.W. Morgan: None. J.D. Isaacs: None. A.G. Wilson: None. K.L. Hyrich: None. A. Barton: None.

Non-Trough Adalimumab and Certolizumab Pegol Serum Drug Levels in Rheumatoid Arthritis Associated with a Therapeutic EULAR Response: Results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGS) Cohort

Non-Trough Adalimumab and Certolizumab Pegol Serum Drug Levels in Rheumatoid Arthritis Associated with a Therapeutic EULAR Response: Results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGS) Cohort

THU0486 Correlating Whole Genome Expression Profiling with Treatment Response in Rheumatoid Arthritis Patients

BackgroundBefore the introduction of biologic drugs rheumatoid arthritis (RA) was traditionally treated with synthetic disease modifying anti-rheumatic drugs (DMARDs) whose mode of action is unclear. Biologics on the other hand,...

OP0257 Differential DNA Methylation Related to Response to Adalimumab and Etanercept in Patients with Rheumatoid Arthritis

BackgroundAnti-TNF therapies have proved a huge advance for the treatment of rheumatoid arthritis (RA), however very good disease control or remission is achieved in just 30% of patients. This makes...

Effect of inadequate adherence on clinical outcomes: results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort

BackgroundAnti-tumour necrosis factor (TNF) therapy has revolutionised patient prognosis in rheumatoid arthritis. In the UK, continuing anti-TNF therapy requires a sustained response as determined by the disease activity score in 28 joints (DAS28). Adherence to disease modifying anti-rheumatic drugs (DMARDs) is low but little is known about adherence to biological therapies and its association to treatment response. We investigated the association of adherence to subcutaneous anti-TNF therapy and DAS28 in people with rheumatoid arthritis. MethodsParticipants were recruited to the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS), a large UK multicentre, prospective, observational, cohort study. Demographic information for patients receiving subcutaneous anti-TNF therapy and disease characteristics were assessed at baseline. Self-reported adherence was defined as whether the biological agent was taken on the day agreed with the health-care professional and recorded at 3 and 6 months. DAS28 was recorded at baseline and after 3 and 6 months of therapy. Descriptive statistics, multivariate logistic regression, and linear regression statistics were used to analyse the data. FindingsData were collected for 392 patients with median disease duration of 7 years (IQR 3–15). Adherence data were collected in 286 patients, of whom 57 (20%) reported non-adherence with biological therapy. Older age, reported adherence at 6 months, and being ever non-adherent during the study period were significantly associated with a poorer DAS28 response to anti-TNF therapy after adjustment for disease duration, age at baseline, sex, concurrent DMARDs, non-steroidal anti-inflammatory drug (NSAID) use, and marital status (p=0·017, p=0·047, and p=0·014, respectively). Logistic regression analysis showed that neither demographic (age, sex, and marital status) nor clinical data (disease duration, NSAID and DMARD use, and baseline DAS28) predicted non-adherence. InterpretationPatients with rheumatoid arthritis who reported not taking their biological drug on the day agreed with their health-care professional had poorer clinical outcomes than did those who did take their drug, emphasising the need for strict adherence to biological therapy in patients with this condition. FundingNIHR Manchester Musculoskeletal Biomedical Research Unit.

OP0051 Differential Methylation Related to Response to Etanercept in Patients with Rheumatoid Arthritis

BackgroundThe introduction of biologic drug therapies targeting specific components of the inflammatory response represents a huge advance in the treatment of rheumatoid arthritis (RA). Despite this, up to 40% of...

THU0009 Reduced Clinical Improvement in Rheumatoid Arthritis Patients Showing IgG1 Allotype -Infliximab Incompatibility

BackgroundIgG1 allotypes (G1m) can induce antibodies in incompatible individuals. Allotypes 1 and 17 are always in the same IgG1 molecule, allotype 2 only appears in IgG1 with allotypes G1m1,17 but...

SAT0014 Correlation of CRP haplotypes with response to anti-TNF therapy in UK patients – results from the BRAGGSS cohort

BackgroundAnti-TNF medication is the most effective treatment method in patients with RA and reduces inflammation by blocking the TNF pathway. However, this treatment is expensive, costing ∼£10,000 per patient, per...

THU0174 Impact of IL-6R and IL-6ST Polymorphisms on Response to Anti-TNF Therapy in UK Patients – Results from the Braggss Cohort

BackgroundAnti-tumour necrosis factor (anti-TNF) biologic therapy is a highly effective yet expensive treatment for patients with Rheumatoid Arthritis (RA). Patient eligibility for therapy and response to treatment is assessed using...

AB0289 Can cd11c expression successfully predict response to etanercept in rheumatoid arthritis patients?

BackgroundThe treatment of rheumatoid arthritis (RA) with biologic drugs such as anti-tumor necrosis factor alpha (TNF) has significantly improved the clinical outcome in patients; however, 30-40% of patients fail to...

Evidence of NLRP3-inflammasome activation in rheumatoid arthritis (RA); genetic variants within the NLRP3-inflammasome complex in relation to susceptibility to RA and response to anti-TNF treatment

BackgroundThe NLRP3-inflammasome, implicated in the pathogenesis of several inflammatory disorders, has been analysed in rheumatoid arthritis (RA).MethodsRelative gene expression of NLRP3-inflammasome components was characterised in PBMCs of 29 patients receiving...