Elena Nikiphorou

A study of baseline prevalence and cumulative incidence of comorbidity and extra-articular manifestations in RA and their impact on outcome

OBJECTIVES To study the prevalence at diagnosis and cumulative incidence of comorbidity in RA, associations with clinical features and impact on outcome. METHODS Standard clinical, laboratory and radiological measures of RA, and details of comorbidity and extra-articular features were recorded at baseline and yearly in an inception cohort of 1460 patients with recently diagnosed RA from nine regions in the UK. The General Practice Research Database was used to compare the incidence of common comorbid conditions (International Classification for Disease-10 codes). RESULTS Baseline prevalence was 31.6% and 8.6% for all comorbidities and extra-articular features, respectively, and 15-year cumulative incidence was 81% and 53%, respectively. Rates of hypertension [standardized incidence ratio (SIR) = 1.61; 95% CI 1.43, 1.79] and ischaemic heart disease (SIR = 1.60; 95% CI 1.35, 1.84) were raised compared with figures for the general population, as was stroke in females (SIR = 1.34; 95% CI 1.02, 1.77) and chronic obstructive pulmonary disorder in males (SIR = 1.63; 95% CI 1.17, 2.26). Comorbidity was associated with risk of both all-cause and cardiovascular mortality (hazard ratio = 1.09; 95% CI 1.02, 1.17) and increased rates of functional decline over 10 years (b = 0.011; 95% CI 0.004, 0.019). Comorbidity was not related to disease activity or structural damage. CONCLUSION Significant comorbidity was present at the outset of RA, increasing with follow-up, mainly in cardiovascular, non-cardiac vascular and respiratory systems. Specific conditions (e.g. hypertension) occurred more frequently than in the general population. Comorbidity was related to mortality and functional decline, and more intensive therapies may need consideration in these patients. As many co-existent conditions are amenable to preventative/therapeutic measures, comorbidity needs earlier detection and management in order to reduce its impact on outcome in RA.

Clinical effectiveness of CT-P13 (Infliximab biosimilar) used as a switch from Remicade (infliximab) in patients with established rheumatic disease. Report of clinical experience based on prospective observational data.

Objective: To gain clinical experience on the effectiveness and safety of switching from infliximab-Remicade(INX) to infliximab-biosimilar-CT-P13(INB) in patients with established rheumatic disease. Methods: Patients receiving INX treatment at a rheumatology clinic consented to switching from INX to INB. Patient reported outcomes (PROs), disease-activity, and inflammatory markers were recorded at every visit. Generalized estimating equation models and time-dependent area under the curve (AUC) before/during INX and INB treatments were employed. Results: Thirty-nine consecutive patients [mean (SD) age 53 (11), 17 F] with various rheumatic diseases were switched to INB after a mean (SD) of 4.1 (2.3) years on INX. Thirty-one patients were on concomitant methotrexate. At a median (range) of 11 (7.5-13) months following the first administration of INB, AUCs for disease activity and PROs were similar for INX and INB. They were better compared to those prior to INX. Eleven patients (28.2%) discontinued INB, due to INX antidrug antibodies detected prior to INB infusion (n = 3); latent tuberculosis (n = 1); new-onset neurofibromatosis (n = 1); subjective reasons with no objective deterioration of disease (n = 6). Conclusion: The clinical effectiveness of INB in both PROs and disease-activity measures was comparable to INX during the first year of switching, with no immediate safety signals. Subjective reasons (negative expectations) may play a role among discontinuations of biosimilars. Larger patient numbers and longer follow-up are necessary for confirming this clinical experience.

Hand and foot surgery rates in rheumatoid arthritis have declined from 1986 to 2011, but large-joint replacement rates remain unchanged: results from two UK inception cohorts.

To assess whether there have been any secular changes in orthopedic interventions in patients with rheumatoid arthritis (RA) since 1986, as examined in 2 early rheumatoid arthritis (RA) inception cohorts with up to 25 years of followup.

Patient global assessment in measuring disease activity in rheumatoid arthritis: a review of the literature

Patient-reported outcomes (PROs) reflect the patient’s perspective and are used in rheumatoid arthritis (RA) routine clinical practice. Patient global assessment (PGA) is one of the most widely used PROs in RA practice and research and is included in several composite scores such as the 28-joint Disease Activity Score (DAS28). PGA is often assessed by a single question with a 0–10 or 0–100 response. The content can vary and relates either to global health (e.g., how is your health overall) or to disease activity (e.g., how active is your arthritis). The wordings used as anchors, i.e., for the score of 0, 10, or 100 according to the scale used, and the timing (i.e., this day or this week) also vary. The different possible ways of measuring PGA translate into variations in its interpretation and reporting and may impact on measures of disease activity and consequently achievement of treat-to-target goals. Furthermore, although PGA is associated with objective measures of disease activity, it is also associated with other aspects of health, such as psychological distress or comorbidities, which leads to situations of discordance between objective RA assessments and PGA. Focusing on the role of PGA, its use and interpretation in RA, this review explores its validity and correlations with other disease measures and its overall value for research and routine clinical practice.

Work disability rates in RA. Results from an inception cohort with 24 years follow-up

OBJECTIVE To explore rates of and reasons for work disability in an early RA cohort with median 10 years follow-up. METHODS One thousand four hundred and sixty patients with early RA (<2 years symptom duration) and no prior DMARD therapy were recruited from nine rheumatology outpatient departments across the UK between 1986 and 1998. Standard clinical, laboratory and radiological assessments were recorded at 6-monthly and yearly intervals. Assessment of employment included details of type and hours of paid work. The main outcomes investigated were rates of and main reasons for work cessation, analysed by age of onset of RA (<45, 45-60 years) and year of recruitment to the study (before or after 1992). RESULTS Maximum follow-up was 24 years, median 10 years. Of 647 patients in paid work at baseline, the majority were <60 years old (91%). The estimated probability of stopping work due to RA was highest in patients with older age of onset (45-60 years) who were recruited before 1992, but improved in those recruited from 1992 to 1998 (P < 0.01). There was no difference seen over the study recruitment years in younger age of onset patients. CONCLUSION Work loss related to RA occurred much earlier than for other reasons, especially in the first 5 years of RA, but improved in the later recruitment period. Work disability is multifactorial, and the gradual changes in therapies used over time in this cohort may be one explanation for the secular differences seen.

Secular Changes in Clinical Features at Presentation of Rheumatoid Arthritis: Increase in Comorbidity But Improved Inflammatory States

To examine secular trends in demographics, clinical manifestations, and comorbidity on first presentation of rheumatoid arthritis (RA) prior to disease‐modifying antirheumatic drug treatment.

Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery: combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds

Objectives To examine the association between disease activity in early rheumatoid arthritis (RA), functional limitation and long-term orthopaedic episodes. Methods Health Assessment Questionnaire (HAQ) disability scores were collected from two longitudinal early RA inception cohorts in routine care; Early Rheumatoid Arthritis Study and Early Rheumatoid Arthritis Network from 1986 to 2012. The incidence of major and intermediate orthopaedic surgical episodes over 25 years was collected from national data sets. Disease activity was categorised by mean disease activity score (DAS28) annually between years 1 and 5; remission (RDAS≤2.6), low (LDAS>2.6–3.2), low-moderate (LMDAS≥3.2–4.19), high-moderate (HMDAS 4.2–5.1) and high (HDAS>5.1). Results Data from 2045 patients were analysed. Patients in RDAS showed no HAQ progression over 5 years, whereas there was a significant relationship between rising DAS28 category and HAQ at 1 year, and the rate of HAQ progression between years 1 and 5. During 27 986 person-years follow-up, 392 intermediate and 591 major surgeries were observed. Compared with the RDAS category, there was a significantly increased cumulative incidence of intermediate surgery in HDAS (OR 2.59 CI 1.49 to 4.52) and HMDAS (OR 1.8 CI 1.05 to 3.11) categories, and for major surgery in HDAS (OR 2.48 CI 1.5 to 4.11), HMDAS (OR 2.16 CI 1.32 to 3.52) and LMDAS (OR 2.07 CI 1.28 to 3.33) categories. There was no significant difference in HAQ progression or orthopaedic episodes between RDAS and LDAS categories. Conclusions There is an association between disease activity and both poor function and long-term orthopaedic episodes. This illustrates the far from benign consequences of persistent moderate disease activity, and supports European League Against Rheumatism treat to target recommendations to secure low disease activity or remission in all patients.

Secular changes in clinical features at presentation of rheumatoid arthritis

To examine secular trends in demographics, clinical manifestations, and comorbidity on first presentation of rheumatoid arthritis (RA) prior to disease‐modifying antirheumatic drug treatment.

Social media use among young rheumatologists and basic scientists: results of an international survey by the Emerging EULAR Network (EMEUNET).

Objectives To explore perceptions, barriers and patterns of social media (SM) use among rheumatology fellows and basic scientists. Methods An online survey was disseminated via Twitter, Facebook and by email to members of the Emerging European League Against Rheumatism Network. Questions focused on general demographics, frequency and types of SM use, reasons and barriers to SM use. Results Of 233 respondents (47 countries), 72% were aged 30–39 years, 66% female. 83% were active users of at least one SM platform and 71% were using SM professionally. The majority used SM for communicating with friends/colleagues (79%), news updates (76%), entertainment (69%), clinical (50%) and research (48%) updates. Facebook was the dominant platform used (91%). SM was reported to be used for information (81%); for expanding professional networks (76%); new resources (59%); learning new skills (47%) and establishing a professional online presence (46%). 30% of non-SM users justified not using SM due to lack of knowledge. Conclusions There was a substantial use of SM by rheumatologists and basic scientists for social and professional reasons. The survey highlights a need for providing learning resources and increasing awareness of the use of SM. This could enhance communication, participation and collaborative work, enabling its more widespread use in a professional manner.

Biologics registers in RA: methodological aspects, current role and future applications

The beginning of the 21st century saw a biopharmaceutical revolution in the treatment of inflammatory rheumatic diseases, particularly rheumatoid arthritis. The fast-evolving use of biologic therapies highlighted the need to develop registers at national and international levels with the aim of collecting long-term data on patient outcomes. Over the past 15 years, many biologics registers have contributed a wealth of data and provided robust and reliable evidence on the use, effectiveness and safety of these therapies. The unavoidable challenges posed by the continuous introduction of new therapies, particularly with regard to understanding their long-term safety, highlights the importance of learning from experience with established biologic therapies. In this Perspectives article, the role of biologics registers in bridging the evidence gap between efficacy in clinical trials and real-world effectiveness is discussed, with a focus on methodological aspects of registers, their unique features and challenges and their role going forward.