AB1165 MEDICATION ADHERENCE DATA IN A RANDOMIZED TRIAL: LARGE CHALLENGES TO COME FROM RAW DATA TO A WORKABLE AND RELIABLE DATASET

Background:Medication adherence in the GLORIA trial, among elderly patients with rheumatoid arthritis, is measured with caps that register openings of the medication bottle. At each study visit, one or two medication bottles with cap (kits) are dispensed, each containing 90 capsules. Multiple steps are needed to come to a workable dataset to describe adherence.Objectives:To describe the steps that are needed to come from raw data to a workable dataset to analyze adherence data that are recorded by electronic caps.Methods:The medication bottle contains a cap with the ability to register cap openings. The raw dataset from the caps consist of an excel file with one opening event per row, recorded as date and time. One cap yields approximately 90 rows. First, the kit numbers were matched to the corresponding patient numbers, that are recorded in another excel file. Instances where two kits were dispensed were recorded with two kit numbers in one cell and need to be copied to two cells with one kit number. Second, the VLOOKUP function was used to combine dates and kit numbers. One row now contains all openings from one kit. Then, the number of days between first opening and each next opening date was calculated. A range of 90 days was made to calculate how many times the bottle was opened on each day of the 90-days period. The results were color-coded to visualize instances of zero, one or ≥two openings on a day.Results:The colored calendar matrix (Figure 1) can now be used to categorize adherence patterns.Conclusion:A monitoring cap seems a simple instrument to measure adherence. However, multiple steps and a lot of time are needed to come to a workable dataset for the study of adherence patterns.Acknowledgments:The GLORIA project is funded by the European Union's Horizon 2020 research and innovation programme under the topic "Personalizing Health and Care'', grant agreement No 634886.Disclosure of Interests:Linda Hartman: None declared, Elisa Alessandri: None declared, Reinhard Bos: None declared, Daniela Opris-Belinski Speakers bureau: as declared, Marc R Kok Grant/research support from: BMS and Novartis, Consultant of: Novartis and Galapagos, Hanneke Griep-Wentink: None declared, Ruth Klaasen: None declared, Cornelia Allaart: None declared, George Bruyn: None declared, Hennie Raterman Grant/research support from: UCB, Consultant of: Abbvie, Amgen, Bristol-Myers Sqibb, Cellgene and Sanofi Genzyme, Marieke Voshaar Grant/research support from: part of phd research, Speakers bureau: conducting a workshop (Pfizer), Nuno Gomes: None declared, Rui Pinto: None declared, Thomas Klausch: None declared, WIllem Lems Grant/research support from: Pfizer, Consultant of: Lilly, Pfizer, Maarten Boers: None declare

A patient-driven registry on Behçet’s disease: the AIDA for patients pilot project

IntroductionThis paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behcet's disease (BD). MethodsThe project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behcet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry. ResultsRespondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behcet's Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0-30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1-50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 & PLUSMN; 1.1 (range - 1.8-4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p < 0.001), the presence of any major organ involvement (p < 0.031), the presence of gastro-intestinal (p < 0.001), neurological (p = 0.012) and musculoskeletal (p = 0.022) symptoms, recurrent fever (p = 0.002), and headache (p < 0.001) were associated to a higher number of accesses to the healthcare system. Multiple linear regression showed that the BDQoL score could significantly predict the global socioeconomic impact of BD (F = 14.519, OR 1.162 [CI 0.557-1.766], p < 0.001). DiscussionPreliminary results from the AIDA for Patients BD registry were consistent with data available in the literature, confirming that PROs and PREs could be easily provided by the patient remotely to integrate physician-driven registries with complementary and reliable information

Development of prediction models to select older RA patients with comorbidities for treatment with chronic low-dose glucocorticoids

Objective: To develop prediction models for individual patient harm and benefit outcomes in elderly patients with RA and comorbidities treated with chronic low-dose glucocorticoid therapy or placebo.Methods: In the Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis (GLORIA) study, 451 RA patients >= 65 years of age were randomized to 2 years 5 mg/day prednisolone or placebo. Eight prediction models were developed from the dataset in a stepwise procedure based on prior knowledge. The first set of four models disregarded study treatment and examined general predictive factors. The second set of four models was similar but examined the additional role of low-dose prednisolone. In each set, two models focused on harm [the occurrence of one or more adverse events of special interest (AESIs) and the number of AESIs per year) and two on benefit (early clinical response/disease activity and a lack of joint damage progression). Linear and logistic multivariable regression methods with backward selection were used to develop the models. The final models were assessed and internally validated with bootstrapping techniques.Results: A few variables were slightly predictive for one of the outcomes in the models, but none were of immediate clinical value. The quality of the prediction models was sufficient and the performance was low to moderate (explained variance 12-15%, area under the curve 0.67-0.69).Conclusion: Baseline factors are not helpful in selecting elderly RA patients for treatment with low-dose prednisolone given their low power to predict the chance of benefit or harm.Pathophysiology and treatment of rheumatic disease

Development of prediction models to select older RA patients with comorbidities for treatment with chronic low-dose glucocorticoids

Objective: To develop prediction models for individual patient harm and benefit outcomes in elderly patients with RA and comorbidities treated with chronic low-dose glucocorticoid therapy or placebo. Methods: In the Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis (GLORIA) study, 451 RA patients >= 65 years of age were randomized to 2 years 5 mg/day prednisolone or placebo. Eight prediction models were developed from the dataset in a stepwise procedure based on prior knowledge. The first set of four models disregarded study treatment and examined general predictive factors. The second set of four models was similar but examined the additional role of low-dose prednisolone. In each set, two models focused on harm [the occurrence of one or more adverse events of special interest (AESIs) and the number of AESIs per year) and two on benefit (early clinical response/disease activity and a lack of joint damage progression). Linear and logistic multivariable regression methods with backward selection were used to develop the models. The final models were assessed and internally validated with bootstrapping techniques. Results: A few variables were slightly predictive for one of the outcomes in the models, but none were of immediate clinical value. The quality of the prediction models was sufficient and the performance was low to moderate (explained variance 12-15%, area under the curve 0.67-0.69). Conclusion: Baseline factors are not helpful in selecting elderly RA patients for treatment with low-dose prednisolone given their low power to predict the chance of benefit or harm.</p

Development of prediction models to select older RA patients with comorbidities for treatment with chronic low-dose glucocorticoids

OBJECTIVE: To develop prediction models for individual patient harm and benefit outcomes in elderly patients with RA and comorbidities treated with chronic low-dose glucocorticoid therapy or placebo. METHODS: In the Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis (GLORIA) study, 451 RA patients ≥65 years of age were randomized to 2 years 5 mg/day prednisolone or placebo. Eight prediction models were developed from the dataset in a stepwise procedure based on prior knowledge. The first set of four models disregarded study treatment and examined general predictive factors. The second set of four models was similar but examined the additional role of low-dose prednisolone. In each set, two models focused on harm [the occurrence of one or more adverse events of special interest (AESIs) and the number of AESIs per year) and two on benefit (early clinical response/disease activity and a lack of joint damage progression). Linear and logistic multivariable regression methods with backward selection were used to develop the models. The final models were assessed and internally validated with bootstrapping techniques. RESULTS: A few variables were slightly predictive for one of the outcomes in the models, but none were of immediate clinical value. The quality of the prediction models was sufficient and the performance was low to moderate (explained variance 12-15%, area under the curve 0.67-0.69). CONCLUSION: Baseline factors are not helpful in selecting elderly RA patients for treatment with low-dose prednisolone given their low power to predict the chance of benefit or harm. TRIAL REGISTRATION: https://clinicaltrials.gov; NCT02585258

Medication adherence in older people with rheumatoid arthritis is lower according to electronic monitoring than according to pill count

Objectives. Suboptimal medication adherence is a serious problem in the treatment of chronic inflammatory diseases. To measure medication adherence, electronic monitoring is regarded as superior to pill count. GLORIA is an ongoing two-year trial on the addition of low-dose (5 mg/d) prednisolone or placebo to standard care in older people (65+ years) with RA. During the entire trial, adherence is measured with electronic caps, and with pill counts. The objective is to describe medication adherence patterns, and to compare the adherence results of the two methods.Methods. The recorded adherence patterns of patients (blinded for treatment group) were classified according to descriptive categories. The cutoff for good adherence was set at 80% of prescribed pills taken.Results. Trial inclusion closed in 2018 at 451 patients, but trial follow-up is ongoing; the current dataset contains adherence data of 371 patients. Mean number of recorded 90-day periods per patient was 4 (range 1-8). Based on pill count over all periods, 90% of the patients had good adherence; based on cap data, only 20%. Cap data classified 30% of patients as non-user (<20% of days an opening) and 40% as irregular user (different adherence patterns, in or between periods).Conclusion. In our trial of older people with RA, the majority appeared to be adherent to medication according to pill count. Results from caps conflicted with those of pill counts, with patterns suggesting patients did not use the bottle for daily dispensing, despite specific advice to do so.Pathophysiology and treatment of rheumatic disease

Low dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+: the pragmatic randomised, double-blind placebo-controlled GLORIA trial

Background Low-dose glucocorticoid (GC) therapy is widely used in rheumatoid arthritis (RA) but the balance of benefit and harm is still unclear.Methods The GLORIA (Glucocorticoid LOw-dose in Rheumatoid Arthritis) pragmatic double-blind randomised trial compared 2 years of prednisolone, 5 mg/day, to placebo in patients aged 65+ with active RA. We allowed all cotreatments except long-term open label GC and minimised exclusion criteria, tailored to seniors. Benefit outcomes included disease activity (disease activity score; DAS28, coprimary) and joint damage (Sharp/van der Heijde, secondary). The other coprimary outcome was harm, expressed as the proportion of patients with >= 1 adverse event (AE) of special interest. Such events comprised serious events, GC-specific events and those causing study discontinuation. Longitudinal models analysed the data, with one-sided testing and 95% confidence limits (95% CL).Results We randomised 451 patients with established RA and mean 2.1 comorbidities, age 72, disease duration 11 years and DAS28 4.5. 79% were on disease-modifying treatment, including 14% on biologics. 63% prednisolone versus 61% placebo patients completed the trial. Discontinuations were for AE (both, 14%), active disease (3 vs 4%) and for other (including covid pandemic-related disease) reasons (19 vs 21%); mean time in study was 19 months. Disease activity was 0.37 points lower on prednisolone (95% CL 0.23, p<0.0001); joint damage progression was 1.7 points lower (95% CL 0.7, p=0.003). 60% versus 49% of patients experienced the harm outcome, adjusted relative risk 1.24 (95% CL 1.04, p=0.02), with the largest contrast in (mostly non-severe) infections. Other GC-specific events were rare.Conclusion Add-on low-dose prednisolone has beneficial long-term effects in senior patients with established RA, with a trade-off of 24% increase in patients with mostly non-severe AE; this suggests a favourable balance of benefit and harm.Pathophysiology and treatment of rheumatic disease