Kathleen Tymms

Objective: We aimed to describe patients’ perspectives and experiences of gout medications to inform patient-centered practice. Method: We performed a systematic review (using MEDLINE, Embase, PsychINFO, and CINAHL databases) and thematic analysis of studies using qualitative methodology from database inception up to May 2023. Results: Five dominant themes were identified in 45 studies involving 1203 patients: denying illness, negotiating uncertainty, juggling competing priorities, minimizing symptoms and lifestyle restrictions, and developing strategies and empowerment. Conclusion: Patients with gout wanted to avoid suffering and lifestyle restrictions but were concerned with stigmatization and were uncertain about medications. Comprehensive information about the disease and reframing the role of the different medications is needed to overcome the barriers of adherence to available and effective treatment. Our results highlight the fundamental importance of maintaining a patient-centered focus and include some avenues of how clinicians may redefine their approach to gout management.

Objective: To describe the trends in remission rates among RA patients in the OPAL dataset, spanning from 2009 to 2022, and provide insights into the effectiveness of evolving RA management approaches in real-world clinical settings. Methods: Patients with a physician diagnosis of RA and at least 3 visits between 1 January 2009 and December 2022 were identified in the OPAL dataset, an aggregated collection of data extracted from the electronic medical records of patients managed by 117 Australian rheumatologists. Demographics, disease history, prescribed medications and proportions of patients in Disease Activity Score 28-joint count C-reactive protein (DAS28CRP)) categories (remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)) were described. Results: A large population (n = 48,388) of eligible patients with RA were identified in the OPAL dataset. A consistent and substantial improvement in DAS28CRP remission rates were found in (i) all patients, (ii) patients managed on conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and (iii) patients treated with biological or targeted synthetic (b/ts)DMARD therapy, increasing from approximately 50% in 2009 to over 70% by 2022. The increase in DAS28CRP remission was accompanied by reduced proportions of patients in MDA and HDA states. Conclusion: This study highlights a consistent improvement in disease activity and rising remission rates among Australian RA patients within the OPAL dataset, offering the potential for enhanced patient outcomes and reduced disease burden. Key Points• The treat-to-target (T2T) approach, with the treatment goal of remission or, as an alternative, a state of LDA, has been widely adopted for the management of RA in Australia.• This study demonstrates an encouraging trend of improved disease activity over time, with remission rates of Australian patients with RA steadily increasing year on year.

Introduction: Sleep disturbance and fatigue are commonly reported in ankylosing spondylitis (AS) but specific prevalence and the relationship to disease control are unknown. Method: This retrospective non-interventional observational study of data from the OPAL dataset included patients with AS (ICD code M45, M45.0 or M08.1), aged 18 to 95 years and had completed ≥ 1 sleep questionnaire between 1 January 2019 and 30 September 2020. The prevalence of insomnia and obstructive sleep apnoea were assessed using the Insomnia Severity Index (ISI) and Multivariate Apnoea Prediction Index (MAPI), respectively. Propensity score (PS) matching based on sex, age and symptom duration increased comparability between patients administered tumour necrosis factor inhibitors (TNFi) and interleukin 17A inhibitors (IL-17Ai). Results: Four hundred ninety-five patients were included. The mean ISI total score in the overall population was 8.6 ± 6.2. Self-reported moderate or severe clinical insomnia was present in 16% and 3.2% of patients, respectively. The mean MAPI score was 0.4 ± 0.3, self-reported apnoea was identified in 31.5% of patients and the mean FACIT-Fatigue score was 36.1 ± 10.7. In the PS matched population, the only treatment-related difference was the mean MAPI score (IL-17Ai 0.4 ± 0.3 and TNFi 0.3 ± 0.2, p = 0.046). Those with poor disease control (BASDAI ≥ 4) were more likely (odds ratio [OR] 7.29, 95% CI 2.37 to 22.46, p = 0.001) to have a greater severity of insomnia symptoms than those with good disease control. Conclusion: In this real-world AS cohort, poor disease control was associated with sleep disturbance. Little difference in sleep disturbance was observed between biologic TNFi and IL-17Ai treatment. Key Points • Sleep disturbance and fatigue are common in patients with ankylosing spondylitis.• In our real-world cohort, self-reported apnoea was reported in one-third of patients; and one in five patients reported moderate to severe insomnia.• Those with poor disease control were more likely to experience greater sleep disturbance than those with good disease control.

Background: Research on adherence interventions in rheumatology is limited by methodological issues, particularly heterogeneous outcomes. We aimed to describe researchers’ experiences with conducting interventional studies targeting medication adherence in rheumatology and their perspectives on establishing core outcomes. Methods: Semi-structured interviews using audio conference were conducted with researchers who had conducted an adherence study of any design in the past 10 years. Data collection and thematic analysis were performed iteratively, until saturation. Results: We interviewed 13 researchers, most of whom worked in academia and specialized in epidemiology and/or health services research. We identified three themes: 1) improving measurement of adherence (considering all phases of adherence, using appropriate and relevant measures, and establishing clinically meaningful thresholds); 2) challenges in designing and appraising adherence intervention studies (considering the confusion over a plethora of outcomes, difficulties with powering studies to demonstrate meaningful changes, and suboptimal descriptions of adherence interventions in published studies); and 3) advancing outcome assessment in adherence intervention studies (capturing rationale for developing a core domain set as well as recommendations and anticipated challenges by participants). Conclusions: Uniquely gathering perspectives from international adherence researchers, our findings led to researcher-informed recommendations for improving adherence research including specifying the targeted adherence phase in designing interventions and studies and providing a glossary of terms to promote consistency in reporting. We also identified recommendations for developing a core domain set for interventional studies targeting medication adherence including involvement of patients, clinicians, and other stakeholders and methodological and practical considerations to establish rigor and support uptake.

Objective: To describe the perspectives of patients with inflammatory arthritis (IA) on outcome domains of trials evaluating medication adherence interventions.Methods: Adult patients (≥ 18 yrs) with IA taking disease-modifying antirheumatic drugs from centers across Australia, Canada, and the Netherlands participated in 6 focus groups to discuss outcome domains that they consider important when participating in medication adherence trials. We analyzed the transcripts using inductive thematic analysis.Results: Of the 38 participants, 23 (61%) had rheumatoid arthritis and 21 (55%) were female. The mean age was 57.3 ± (SD 15.0) years. Improved outcome domains that patients wanted from participating in an adherence trial were categorized into 5 types: medication adherence, adherence-related factors (supporting adherence; e.g., medication knowledge), pathophysiology (e.g., physical functioning), life impact (e.g., ability to work), and economic impact (e.g., productivity loss). Three overarching themes reflecting why these outcome domains matter to patients were identified: how taking medications could improve patients’ emotional and physical fitness to maintain their social function; how improving knowledge and confidence in self-management increases patients’ trust and motivation to take medications as agreed with minimal risk of harms; and how respect and reassurance, reflecting health care that values patients’ opinions and is sensitive to patients’ individual goals, could improve medication-taking behavior.Conclusion: Patients value various outcome domains related to their overall well-being, confidence in medication use, and patient–healthcare provider relationships to be evaluated in future adherence trials.

Objective: To assess the impact of anti-citrullinated protein antibody (ACPA) serostatus on response to treatment with either tumor necrosis factor inhibitors (TNFi) or abatacept in patients with rheumatoid arthritis (RA). Methods: Data was obtained from the Optimizing Patient outcomes in Australian RheumatoLogy (OPAL) dataset. Patient data were included in the analysis if they commenced treatment with abatacept or TNFi between 01 August 2006 and 30 June 2017 and had at least 12 months’ follow-up. The primary outcome was the mean change in the clinical disease activity index (CDAI) score from baseline to 12 months. Results: A total of 2,052 patients were included of which 1,415 were in the TNFi cohort (n=1,053 ACPA positive) and 637 in the abatacept cohort (n=445 ACPA positive). Patients were predominantly female (75% TNFi; 80% abatacept) with no significant difference in age between cohorts. Patients with ACPA positivity had longer disease duration before commencing treatment in both the TNFi and abatacept cohorts compared to ACPA negative patients. No difference in disease severity was observed in those with ACPA negativity compared to those with ACPA positivity. Patients treated with TNFi and abatacept had significantly improved mean change in CDAI after 12 months; ACPA positivity was associated with greater response to treatment with abatacept compared to that in patients with ACPA negativity (p=0.011). No difference in response was observed based on ACPA serostatus in patients treated with TNFi (p=0.73). Conclusion: Baseline ACPA positivity was associated with improved clinical response using CDAI outcome measure at 12 months for abatacept but not for TNFi therapies. Cite this article as: Tymms K, Butcher B, Smith T, Littlejohn G, OPAL Consortium. Impact of anti-citrullinated protein antibody on tumor necrosis factor inhibitor or abatacept response in patients with rheumatoid arthritis. Eur J Rheumatol 2021; 8(2): 67-72.

Objective.: Nonadherence to medications is common in rheumatic conditions and associated with increased morbidity. Heterogeneous outcome reporting by researchers compromises the synthesis of evidence of interventions targeting adherence. We aimed to assess the scope of outcomes in interventional studies of medication adherence.Methods.: We searched electronic databases to February 2019 for published randomized controlled trials and observational studies of interventions with the primary outcome of medication adherence including adults with any rheumatic condition, written in English. We extracted and analyzed all outcome domains and adherence measures with prespecified extraction and analysis protocols.Results.: Overall, 53 studies reported 71 outcome domains classified into adherence (1 domain), health outcomes (38 domains), and adherence-related factors (e.g., medication knowledge; 32 domains). We subdivided adherence into 3 phases: initiation (n = 13 studies, 25%), implementation (n = 32, 60%), persistence (n = 27, 51%), and phase unclear (n = 20, 38%). Thirty-seven different instruments reported adherence in 115 unique ways (this includes different adherence definitions and calculations, metric, and method of aggregation). Forty-one studies (77%) reported health outcomes. The most frequently reported were medication adverse events (n = 24, 45%), disease activity (n = 11, 21%), bone turnover markers/physical function/quality of life (each n = 10, 19%). Thirty-three studies (62%) reported adherence-related factors. The most frequently reported were medication beliefs (n = 8, 15%), illness perception/medication satisfaction/satisfaction with medication information (each n = 5, 9%), condition knowledge/medication knowledge/trust in doctor (each n = 3, 6%).Conclusion.: The outcome domains and adherence measures in interventional studies targeting adherence are heterogeneous. Consensus on relevant outcomes will improve the comparison of different strategies to support medication adherence in rheumatology.

Objective.: The OMERACT-Adherence meeting was convened to discuss the conceptual and methodological challenges in developing a core domain set (Adherence-CDS) for trials of interventions for medication adherence in rheumatology.Methods.: Forty participants from nine countries participated.Results.: Four ideas emerged: for adherence trials, the Adherence-CDS could include adherence and the condition-specific CDS; many factors affect adherence and are intervention targets, contextual factors, or outcome domains; adherence is a critical factor in drug trials; and standardized adherence measures are needed.Conclusion.: Despite the challenges, the meeting clarified an approach to developing an Adherence-CDS that complements existing OMERACT work and methodology.

The aim was to describe the real-world treatment persistence of subcutaneous TNF inhibitors (TNFi) for patients with inflammatory rheumatic disease newly initiating treatment with biologic disease-modifying antirheumatic drugs (bDMARD). This was a retrospective cohort study that extracted data for new users of TNFi between 1 August 2010 and 31 August 2016 from the Australian Optimising Patient outcome in Australian RheumatoLogy (OPAL) registry. Patients were 1:1 propensity-score matched with golimumab based on their age, sex, year of index, C-reactive protein level, baseline treatment combination and disease. Treatment persistence was calculated. Data from 3749 patients were extracted (adalimumab n = 1518; certolizumab n = 298; etanercept n = 1068; golimumab n = 865). The mean (SD) ages of patients were 51.7 (14.2) years for adalimumab, 53.7 (14.0) years for certolizumab, 52.8 (14.3) years for etanercept and 52.3 (14.6) years for golimumab, with disease durations 7.7 (10.5), 8.8 (9.2), 8.1 (10.4) and 7.3 (9.7) years, respectively. Two thirds of the patients were women. There was no significant difference in treatment persistence by treatment in the overall population (adalimumab 33.6 [95% CI 28.6–40.7], certolizumab 24.8 [95% CI 21.3–42.1], etanercept 27.6 [95% CI 23.4–36.5], golimumab 30.3 [95% CI 23.26–36.5]; months, p = 0.545), or in the propensity score-matched population. No safety signals were detected. In this real-world biologic-naïve Australian inflammatory rheumatic disease cohort treated with subcutaneous TNF inhibitors during the period 2010–2016, there was no difference in treatment persistence between agents.

Aim: To describe the persistence of biologic disease modifying anti‐rheumatic drugs (bDMARDs) in Australian rheumatoid arthritis (RA) patients, and assess the influence of methotrexate and other conventional DMARD (cDMARD) concomitant medications, and treatment line on bDMARD persistence and glucocorticoids usage.Method: RA patients, from the 10% Australian Medicare random sample, aged ≥18 for whom bDMARDs were dispensed were included. Individual sub‐cutaneous (SC) anti‐tumor necrosis factor‐α (anti‐TNFα) agents were combined as they were equivalent.Results: Data from 1230 patients were analyzed. For all patients the 12‐month persistence rates (based on Kaplan–Meier estimates) were 76% for intravenous (IV) tocilizumab, 63% abatacept (SC/IV), 61% SC‐anti‐TNFs and 36% IV‐infliximab. Persistence rates on first‐line bDMARDs were 79% (tocilizumab and abatacept), 64% (SC‐anti‐TNFs) and 13% (infliximab); rates were sustained for tocilizumab but dropped to 49% for abatacept and 51% for SC‐anti‐TNFs in the second‐line setting. Median treatment persistence was 40 months tocilizumab (95% CI: 30‐ND), 33 months abatacept (95% CI: 20‐ND); 22 months SC‐anti‐TNF (95% Cl: 18–27), and 4 months infliximab (95% CI: 2–13). Longer persistence was observed for SC‐anti‐TNFs and abatacept combined with methotrexate or other cDMARDs. For tocilizumab, persistence was robust with or without concomitant medications. The median oral glucocorticoid doses decreased from 4.1 mg/day (min 0, max 21) to 2.0 mg/day (min 0, max 17.3) over 2 years.Conclusions: Treatment persistence was longer on tocilizumab followed by abatacept then SC‐anti‐TNF therapy and was influenced by co‐therapy. Glucocorticoid dosage decreased with bDMARD use. This real‐world data highlights that persistence on bDMARDs differs according to biologics mode of action and co‐therapy.