Search

Objective: To describe obstetric outcomes based on COVID-19 vaccination status, in women with rheumatic and musculoskeletal diseases (RMDs) who developed COVID-19 during pregnancy., Methods: Data regarding pregnant women entered into the COVID-19 Global Rheumatology Alliance registry from 24 March 2020-25 February 2022 were analysed. Obstetric outcomes were stratified by number of COVID-19 vaccine doses received prior to COVID-19 infection in pregnancy. Descriptive differences between groups were tested using the chi-squared or Fisher's exact test., Results: There were 73 pregnancies in 73 women with RMD and COVID-19. Overall, 24.7% (18) of pregnancies were ongoing, while of the 55 completed pregnancies, 90.9% (50) of pregnancies resulted in livebirths. At the time of COVID-19 diagnosis, 60.3% (n = 44) of women were unvaccinated, 4.1% (n = 3) had received one vaccine dose while 35.6% (n = 26) had two or more doses. Although 83.6% (n = 61) of women required no treatment for COVID-19, 20.5% (n = 15) required hospital admission. COVID-19 resulted in delivery in 6.8% (n = 3) of unvaccinated women and 3.8% (n = 1) of fully vaccinated women. There was a greater number of preterm births (PTB) in unvaccinated women compared with fully vaccinated 29.5% (n = 13) vs 18.2% (n = 2)., Conclusions: In this descriptive study, unvaccinated pregnant women with RMD and COVID-19 had a greater number of PTB compared with those fully vaccinated against COVID-19. Additionally, the need for COVID-19 pharmacological treatment was uncommon in pregnant women with RMD regardless of vaccination status. These results support active promotion of COVID-19 vaccination in women with RMD who are pregnant or planning a pregnancy., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: MTX remains the cornerstone for therapy for RA, yet research shows that non-adherence is significant and correlates with response to therapy. This study aimed to halve self-reported non-adherence to MTX at the Kellgren Centre for Rheumatology., Methods: An anonymous self-report adherence questionnaire was developed and data collected for 3 months prior to the introduction of interventions, and then regularly for the subsequent 2.5 years. A series of interventions were implemented, including motivational interviewing training, consistent information about MTX and development of a summary bookmark. Information on clinic times was collected for consultations with and without motivational interviewing. Surveys were conducted to ascertain consistency of messages about MTX. A biochemical assay was used to test MTX serum levels in patients at two time points: before and 2.8 years following introduction of the changes. Remission rates at 6 and 12 months post-MTX initiation were retrieved from patient notes and cost savings estimated by comparing actual numbers of new biologic starters compared with expected numbers based on the numbers of consultants employed at the two time points., Results: Between June and August 2016, self-reported non-adherence to MTX was 24.7%. Following introduction of the interventions, self-reported non-adherence rates reduced to an average of 7.4% between April 2018 and August 2019. Clinic times were not significantly increased when motivational interviewing was employed. Consistency of messages by staff across three key areas (benefits of MTX, alcohol guidance and importance of adherence) improved from 64% in September 2016 to 94% in January 2018. Biochemical non-adherence reduced from 56% (September 2016) to 17% (June 2019), whilst remission rates 6 months post-initiation of MTX improved from 13% in 2014/15 to 37% in 2017/18, resulting is estimated cost savings of £30 000 per year., Conclusion: Non-adherence to MTX can be improved using simple measures including focussing on the adherence and the benefits of treatment, and providing consistent information across departments., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To identify different trajectories of disease activity in patients with RA following initiation of a first anti-TNF., Methods: Patients with RA starting their first anti-TNF between 2001 and 2013 were selected from the British Society for Rheumatology Biologics Register for RA. Six-monthly DAS28-ESR scores were used to identify trajectories of disease activity using latent class modelling. Data were included for six follow-ups after registration (approximately 3 years). Subgroup analysis examined changes in disease activity profiles over time., Results: A total of 14 436 patients with RA starting their first anti-TNF were enrolled between 2001 and 2013 (13 115 between 2001 and 2008, 1321 between 2010 and 2013). The mean number of DAS28-ESR scores was 3.5/patient (s.d. 2.1), with a mean of 184.9 days (s.d. 69.9) between scores. The DAS28-ESR nadir was achieved within 250 days of commencing anti-TNF, although apparent trajectory divergence emerged by first 6-monthly follow-up at 180 days. Four distinct response trajectories comprised the most stable model. Most patients fitted into 'modest' (7986 patients; 55.3%) or 'substantial' (4676 patients; 32.4%) response trajectories. Of the remainder, 1254 (8.7%) and 520 (3.6%) fitted 'maximal' and 'minimal' response trajectories, respectively. There was a significant (P < 0.01) increase in proportion achieving 'maximal' response between 2001-2008 and 2010-2013., Conclusion: This is the largest study to identify long-term response trajectories with anti-TNF. By 6 months, longer-term trajectory profiles of DAS28 could already be identified, with many patients identified earlier. The majority of patients had persistent moderate response, equivalent to maintained DAS28-ESR moderate disease activity. The maximal response trajectory (equivalent to sustained DAS2-ESR remission) was only achieved by approximately one-third of patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: To investigate the frequency and predictors of sustained 28-joint DAS (DAS28) remission and low disease activity (LDA) in patients receiving anti-TNF therapy and changes in responses over a 12 year period., Methods: Data from the British Society for Rheumatology Biologics Registry for Rheumatoid Arthritis were used. Sustained remission and LDA were defined according to DAS28-ESR thresholds sustained for 6 months. The dataset was dichotomized into sequential chronological subgroups (2001-2010 and 2010-2013). Predictive variables were identified from a previous systematic review and modelled using multivariable logistic regression., Results: Overall, 2144 (14.9%) and 3802 (26.3%) patients achieved sustained remission or LDA, respectively. Positive predictors of sustained remission/LDA included adalimumab (vs etanercept), greater patient global assessment, never- and ex-smoker status (vs current smoking), greater swollen joint count, more recent commencement of anti-TNF and MTX co-prescription (except in the 2010-2013 subgroup). Negative predictors of sustained remission and LDA included poor baseline functional status (HAQ), female gender, older age at starting anti-TNF, infliximab use (vs etanercept), increasing BMI and greater baseline ESR. Increasing tender joint count was negatively associated with sustained LDA only. The overall proportion of patients achieving sustained remission and LDA has increased significantly over time., Conclusion: Sustained remission/LDA on anti-TNF treatment remains uncommon. Adalimumab use, greater patient global assessment, never- and ex-smoker status, greater swollen joint count, more recent commencement of anti-TNF and MTX co-prescription are associated with achievement of sustained remission/LDA. However, co-prescription of MTX was not associated with an increased likelihood of achieving sustained remission or LDA in the analysis of more recent anti-TNF responses., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Previous ecological data suggest a decline in the need for joint replacements in RA patients following the introduction of TNF inhibitor (TNFi) therapy, although patient-level data are lacking. Our primary aim was to estimate the association between TNFi use and subsequent incidence of total hip replacement (THR) and total knee replacement., Methods: A propensity score matched cohort was analysed using the British Society for Rheumatology Biologics Registry (2001-2016) for RA data. Propensity score estimates were used to match TNFi users to similar conventional synthetic DMARD users (with replacement) using a 1:1 ratio. Weighted multivariable Cox regression was used to estimate the impact of TNFi on study outcomes. Effect modification by baseline age and disease severity were investigated. Joint replacement at other sites was also analysed. An instrumental variable sensitivity analysis was also performed., Results: The matched analysis contained a total of 19 116 patient records. Overall, there was no significant association between TNFi use vs conventional synthetic DMARD on rates of THR (hazard ratios = 0.86 [95% CI: 0.60, 1.22]) although there was significant effect modification by age (P < 0.001). TNFi was associated with a reduction in THR among those >60 years old (hazard ratio = 0.60 [CI: 0.41, 0.87]) but not in younger patients. No significant associations were found for total knee replacement or other joint replacement., Conclusion: Overall, no association was found between the use of TNFi and subsequent incidence of joint replacement. However, TNFi was associated with a 40% relative reduction in THR rates among older patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: To evaluate determinants of discordance between DAS28-ESR and DAS28-CRP and resulting impact on disease activity stratification in RA., Methods: Paired DAS28-ESR and DAS28-CRP readings (n = 31 074) were obtained from the British Society for Rheumatology Biologics Register for RA. Factors influencing discordance between DAS28-ESR and DAS28-CRP were evaluated alongside the resulting effect on disease activity stratification. The impact of gender adjustment to the DAS28-CRP was evaluated., Results: DAS28-CRP scores were ∼0.3 lower than DAS28-ESR overall, with greatest differences for women (-0.35) and patients over 50 years old (-0.34). Mean male DAS28-CRP scores were 0.15 less than corresponding DAS28-ESR scores. Discordance between DAS28-ESR and DAS28-CRP significantly impacted disease activity stratification at low disease activity and remission thresholds (32.0% and 66.6% concordance, respectively). Adjusting DAS28-CRP scores by gender significantly (P < 0.001) improved agreement with the DAS28-ESR., Conclusion: Discordance between DAS28-ESR and DAS28-CRP is greatest for women and patients over 50 years of age, and influences disease activity stratification. The proposed gender-adjusted DAS28-CRP improves inter-score agreement with DAS28-ESR, supporting more reliable disease activity stratification in treat-to-target approaches for RA., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: To determine if depressive symptoms assessed near diagnosis associate with future measures of pain, disability and disease for adolescent patients diagnosed with JIA., Methods: Data were analysed from JIA patients aged 11-16 years recruited to the Childhood Arthritis Prospective Study, a UK-based inception cohort of childhood-onset arthritis. Depressive symptoms (using the Mood and Feelings Questionnaire; MFQ), active and limited joint count, disability score (Childhood Health Assessment Questionnaire), pain visual analogue scale and patient's general evaluation visual analogue scale were collected. Associations between baseline measures (first visit to paediatric rheumatologist) were analysed using multiple linear regression. Linear mixed-effect models for change in the clinical measures of disease over 48 months were estimated including MFQ as an explanatory variable., Results: Data from 102 patients were analysed. At baseline, median (IQR) age was 13.2 years (11.9-14.2 years) and 14.7% scored over the MFQ cut-off for major depressive disorder. At baseline, depressive symptoms significantly associated with all clinical measures of disease (P ⩽ 0.01). High baseline depressive symptoms scores predicted worse pain (P ⩽ 0.005) and disability (P ⩽ 0.001) 12 months later but not active and limited joint counts., Conclusions: Adolescent patients with JIA and depressive symptoms had more active joints, pain and disability at the time of their first specialist appointment. The associations between baseline depression and both pain and disability continued for at least one year, however, this was not the case for active joint count.

Objectives: To establish the rate of recurrent infection in RA patients recruited to the British Society for Rheumatology Biologics Register - Rheumatoid Arthritis. Secondary objectives were to establish whether the organ class of index infection predicted future serious infection (SI)., Methods: Using data from the British Society for Rheumatology Biologics Register - Rheumatoid Arthritis, a prospective observational cohort, we identified patients with at least one episode of SI. Incidence rates of SI, recurrent SI within the same organ class as the index infection and recurrent SI (of any class) were calculated. A Cox proportional hazards model was used to identify predictors of SI., Results: In total, 5289 subjects with at least one SI contributing 19 431 patient-years follow-up were studied. The baseline annual rate of first SI was 4.6% (95% CI: 4.5, 4.7), increasing to 14.1% (95% CI: 13.5, 14.8) following an index infection. Respiratory infections were the most frequent (44% of all events). Recurrent infections mirrored the organ class of the index infection. Sepsis, increasing age and polypharmacy were significant predictors of infection recurrence in a fully adjusted model. The system class of index infection was associated with the risk of a recurrent event; subjects who experienced sepsis had the highest risk of subsequent SI within 12 months, 19.7% (95% CI: 15.1, 25.7)., Conclusion: Recurrent infections in RA are common. Understanding patterns and predictors of recurrent infection together with the differential infection risk associated with immunosuppressive agents will help personalize RA care, tailor treatment choices better and mitigate against episodes of SI.

Objective: The aim was to correlate protein concentrations of S100A9 in pretreatment serum samples with response to the tumour-necrosis factor (TNF) inhibitor drugs etanercept in a large UK replication cohort., Methods: Pretreatment serum samples from patients with RA (n = 236) about to commence treatment with etanercept had S100A9 serum concentration measured using an ELISA. Following the experimental procedure, S100A9 concentrations were analysed with respect to EULAR response., Results: No evidence of association between S100A9 concentration and EULAR response to the TNF-inhibitor biologic drug etanercept was observed following multinomial logistic regression analysis (non-responder vs moderate responder, P = 0.957; and non-responder vs good responder, P = 0.316). Furthermore, no significant associations were observed when correlating pretreatment S100A9 concentrations with clinical parameters of disease activity (P > 0.05)., Conclusion: In the largest replication cohort conducted to date, no evidence for association was observed to support the use of S100A9 as a clinical biomarker predictive of response to the TNF-inhibitor biologic drug etanercept., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: A high incidence of pancreatic cancer (PCa) in patients exposed to was observed in the German biologics register. To evaluate this possible safety signal, a concerted analysis with the national biologics registers in the UK and Sweden was performed., Methods: Patients with enrolled in the British Society of Rheumatology Biologics Register (BSRBR), the Swedish Rheumatology Register (SRR) or the German Biologics Register [Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT)] were analysed. The patients were exposed to biologic or conventional DMARDs. Outcomes were obtained from physician reports, health authorities and via linkage to national cancer and death registers. Age- and gender-standardized incidence ratios (SIRs) of PCa were calculated based on the expected rates available from the individual national cancer registers., Results: Data from 5126 (Germany), 16 930 (UK) and 19 351 (Sweden) RA patients were available for the analysis. The highly discrepant prescription rates of LEF in the respective countries resulted in 11 343 (Germany), 30 787 (UK) and 2518 (S) patient-years of exposure to LEF. Compared with the general population, the incidence of PCa in patients ever exposed to LEF corresponded to a SIR of 3.1 (95% CI 1.3, 6.5) in Germany, 1.05 (95% CI 0.5, 2.1) in the UK and 1.8 (95% CI 0.1, 10.2) in Sweden., Conclusion: The results of the replication analyses do not support the hypothesis of an increased risk of PCa in patients exposed to treatment with LEF. However, they do not completely rule out concerns, and therefore further verification in other data sets is recommended.

Objectives: Small studies have shown an improvement in disease activity in patients with RA who have switched between anti-TNF therapies for reasons of inefficacy. However, it is not clear whether switching improves longer term outcomes, such as disability. This analysis compares changes in HAQ scores 1 yr following lack of response to a first anti-TNF based on subsequent treatment during that year., Methods: Analysis was limited to RA patients with inefficacy to a first anti-TNF based on (i) clinician opinion and/or (ii) disease activity score in 28 joints and had an HAQ measured at time of non-response and 12 months later. Patients were classified into three groups based on treatment during the next 12 months: (i) continued anti-TNF despite non-response; (ii) stopped anti-TNF with no further biologics; and (iii) switched to a second anti-TNF. Mean improvement in HAQ was compared among the groups using multivariable linear regression models., Results: As of July 2006, 868 patients met the inclusion for this analysis. Four hundred and seventy-nine patients stopped anti-TNF of whom 331 switched to a second anti-TNF. Three hundred and eighty-nine continued treatment. Patients who continued and those who switched had improvements in HAQ over the 12 months, unlike patients who discontinued all biologic therapy. The best improvement was seen in those who switched [adjusted mean improvement in HAQ 0.15 (95% CI 0.26, 0.05)]., Conclusion: There is a significant improvement in HAQ in patients who switch to a second anti-TNF, providing an effective next choice of therapy for some patients who fail to respond to their first anti-TNF.

Objectives: To study the association between disease severity at first presentation to paediatric rheumatology (PRh) and length of time since symptom onset in children recruited to the Childhood Arthritis Prospective Study., Methods: Children or=2 weeks were recruited from five UK hospitals. Data including demographics, disease features, Childhood Health Assessment Questionnaire (CHAQ), physician and parent global assessment and blood tests were collected at the first appointment with PRh (baseline). The association between symptom duration (defined as time from first reported symptom onset to presentation at PRh) and baseline disease characteristics was evaluated using non-parametric descriptive statistics and multivariable logistic regression analyses., Results: Five hundred and seven children (65% female) were included: median age at onset was 6.8 yrs. Two hundred and thirty-three had oligoarthritis, 68 had RF-negative polyarthritis, 27 had systemic onset arthritis and 29 had arthritis that was not JIA. The median symptom duration was 4.6 months. Median symptom duration was shortest for children presenting with systemic arthritis (1.6 months) and longest for those with PsA (8.6 months). Children with a longer duration of symptoms were older and had higher median active joint counts but lower median ESR. Symptom duration did not correlate with CHAQ score at presentation., Conclusions: Children who have systemic arthritis had the shortest delay to PRh presumably because they are profoundly unwell. Children with joint pain/stiffness but normal ESR had longer delays suggesting that if blood tests do not indicate inflammation, the diagnosis of JIA may be overlooked.

Background: Anti-tumour necrosis factor-alpha (TNF-alpha) therapies represent an important advancement in therapy for rheumatoid arthritis (RA). However, there remains a proportion of patients who do not improve despite therapy. These drugs are expensive and have the potential of serious toxicity. Therefore, it would be ideal to predict the patients who will respond, so that the use of these drugs can be targetted., Objective: To identify the clinical factors present at the start of anti-TNF-alpha therapy that are associated with response at 6 months in patients with RA., Methods: The British Society for Rheumatology (BSR) Biologics Register collects detailed data on all patients with a rheumatic disease receiving biologic therapy in the UK. We studied all patients with RA who had started etanercept (ETA) or infliximab (INF) and had achieved a minimum 6 months follow-up by 1 October, 2004. The disease status at the baseline and at 6 months was assessed using the Disease Activity Score (DAS28). The response was classified according to the European League against Rheumatism (EULAR) improvement criteria. The effect of baseline characteristics on response was studied using multivariate ordinal logistic regression., Results: 2879 patients were included in this analysis (1267 ETA, 1612 INF). At the start of therapy, the mean age was 55 yrs, disease duration 14 yrs, baseline DAS28 6.7 and health assessment questionnaire (HAQ) 2.1. In all, 28% of ETA and 86% of INF patients were receiving methotrexate. After 6 months, 18% had a good EULAR response, of whom 9% were considered to be in remission and 50% had a moderate response. There was no overall difference in response rate between the two anti-TNF-alpha therapies. A higher baseline HAQ score correlated with a lower response rate while a better response was associated with the current use of NSAIDs and the use of methotrexate (MTX), although the latter only reached statistical significance with ETA [OR 1.82 (95% CI 1.38-2.40)]. There was a lower response rate among current smokers, particularly in patients receiving INF [OR 0.77 (95% CI 0.60-0.99)]. Age, disease duration, rheumatoid factor and the previous number of disease-modifying antirheumatic drugs (DMARDs) did not predict response to either drug. However, females were less likely to achieve remission., Conclusions: These data support an improved outcome among patients receiving MTX in combination with anti-TNF-alpha therapies. However, the most disabled patients were less likely to respond, despite concurrent MTX. The benefits of NSAIDs may reflect the relative absence of comorbidities in patients who can tolerate these drugs or the continuing presence of reversible inflammatory symptoms. The association of smoking and poor outcome with INF is a novel finding and may reflect alterations in pharmacokinetics. The inability of other baseline disease characteristics to predict the outcome suggests that other factors, including potential genetic differences in drug metabolism, may be influencing the response to anti-TNF-alpha therapies.