Outcomes following switching from etanercept originator to etanercept biosimilar in 1024 RA patients: A matched-analysis of the BSRBR-RA.

OBJECTIVES: Adults with RA are being switched from etanercept originator to biosimilar in non-medical/cost-saving switching. This analysis aims to investigate outcomes in these patients, including (a) drug survival and (b) disease activity at six and 12-month, compared with those who remain on originator. METHODS: Using BSRBR-RA, those who switched directly from etanercept originator to biosimilar were identified and matched to patients receiving originator, based on gender, age, disease duration, originator start year. Drug survival was calculated; Cox-proportional hazard models assessed differences in drug persistence between those who switched versus remaining on originator. Change in DAS28 after six and 12-months was compared between cohorts. Multiple imputation was used. RESULTS: 1024 adults with RA switching from etanercept originator to biosimilar were included, with a matched cohort of patients remaining on originator. Patients who switched onto a biosimilar product were no more likely to discontinue etanercept treatment versus those who remained on originator; hazard ratio 1.06 (95%CI 0.89-1.26), with 65% of patients remaining on treatment at three years. Ninety-five (9%) patients switched back to originator within the first year. After six and 12-months, biosimilar patients were no more likely to have a worsening of DAS28 (>0.6units) compared with those who remained on originator. CONCLUSIONS: This is the largest matched comparative effectiveness analysis showing patients switched from etanercept originator to biosimilar appear to do just as well with regards to disease activity and drug persistence compared with those who remained on originator. These data will be reassuring to clinicians and patients regarding non-medical switching.

Evaluation of serious infections, including Mycobacterium tuberculosis, during treatment with biologic disease-modifying antirheumatic drugs: does line of therapy matter?

OBJECTIVES: This study aimed to evaluate if and how the incidence of serious infection (SI) and active tuberculosis (TB) differ among seven biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) considering the line of therapy. METHODS: Patients with RA from the British Society for Rheumatology Biologics Register-RA cohort who initiated etanercept, certolizumab, infliximab, adalimumab, abatacept, rituximab, or tocilizumab from the first to fifth line of therapy were included. Follow-up extended up to three years. Primary outcome was SI, secondary outcome was TB. Event rates were calculated and compared using Cox proportional-hazards, controlling for confounding with inverse probability of treatment weights. Comparisons were made overall and stratified by line of therapy. Sensitivity analysis restricted to all treatment courses from 2009 (tocilizumab availability) until end of study (2018). RESULTS: Among 33 897 treatment courses (62 513 patient-years) the incidence of SI was 4.4/100 patient-years (95%CI 4.2-4.5). After adjustment, hazards ratios (HR) of SI were slightly higher with adalimumab and infliximab compared with etanercept. However, no clear pattern was observed when stratifying by line of therapy, in terms of incidence rate or hazards ratio. Sensitivity analyses showed similar HR among these treatments. Regarding TB, all 49 cases occurred during the first three lines of treatment and rarely since 2009. CONCLUSION: The risk of serious infections does not appear to be influenced by the line of therapy in patients with RA. However, the risk of tuberculosis seems to be more frequent during the initial lines of treatment or prior to 2009.

Etanercept originator versus etanercept biosimilar for the treatment of rheumatoid arthritis as a first biologic: results from the BSRBR-RA.

OBJECTIVES: Etanercept biosimilars show comparable efficacy to their originators among biologic-naïve patients with RA in randomized controlled trials. Nationwide guidelines have obligated prescribing of etanercept biosimilars from 2016, resulting in significant cost savings. This analysis aimed to compare the effectiveness of etanercept originator vs etanercept biosimilar amongst biologic-naïve RA patients treated in routine clinical practice in the UK. METHODS: Biologic-naïve RA patients starting etanercept in the British Society for Rheumatology Biologics Register in Rhematoid Arthritis (BSRBR-RA) cohort study from 2010 were included. Data collected at start of therapy includes patient demographics and disease activity. Follow-up data includes changes in disease activity and anti-rheumatic therapy. Six- and 12-month primary outcomes include DAS for 28-joints (DAS28) remission, EULAR response and minimal clinically important difference in function. Etanercept drug survival was assessed using Kaplan-Meier and Cox regression, including reasons for treatment withdrawal. Multiple imputation accounted for missing data. Propensity-decile adjustment was used to account for confounding by indication. RESULTS: A total of 1806 biologic-naïve RA patients started etanercept: 1009 originator, 797 biosimilar. At 6 and 12 months, the proportion of patients achieving DAS28 remission and EULAR response were similar between treatments. During follow-up, 19% of originator patients switched onto etanercept biosimilar. Patients were censored at time of switch. Patients on originator were no more likely to stop therapy vs biosimilar; 71% of originator and 76% of biosimilar patients remained on therapy at 1 year. CONCLUSIONS: In one of the largest analyses of patients with RA, biologic-naïve RA patients treated with etanercept originator showed similar outcomes vs biosimilar using real-world data. Drug survival, and disease activity after 6 and 12 months of therapy, was similar between cohorts.

Cervical screening uptake and rates of cervical dysplasia in the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

OBJECTIVES: To compare cervical screening attendance and cytology (high- and low-grade cervical dysplasia [HGCD and LGCD]) between women with RA and the English general population and between biologic DMARD (bDMARD)-naïve and exposed women. METHODS: The British Society for Rheumatology Biologics Register for RA (BSRBR-RA), a national prospective study of RA treatment outcomes, was linked to the National Health Service Cervical Screening Programme, providing data for 12 785 women to compare with national screening data. Rates of HGCD/LGCD were compared with rates of negative smears using risk difference calculations between BSRBR-RA and national statistics. Within the BSRBR-RA, coverage was compared between those with low and high physical disability scores, while coverage and cytology results were compared between bDMARD-naïve and -exposed RA patients. RESULTS: The mean 5 year screening coverage was significantly higher in BSRBR-RA (83%) compared with the general population (79%), but lower in women with high disability (78%) compared with lesser disability (85%). Risk differences for HGCD were lower in the BSRBR-RA compared with national statistics, whereas risk differences for LGCD were higher. There was no statistically significant difference in the rates of HGCD or LGCD between bDMARD-exposed and -naïve women. CONCLUSION: This first-ever British analysis of cervical screening rates in RA has shown that women with RA have higher screening rates than the general population. Disability negatively impacts attendance, but treatment type does not. Women with RA did not have an increased risk of HGCD compared with national statistics, which was also not influenced by bDMARD exposure.

Biologic refractory disease in rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

OBJECTIVES: Biologic disease-modifying antirheumatic drugs (bDMARDs) have revolutionised treatment and outcomes for rheumatoid arthritis (RA). The expanding repertoire allows the option of switching bDMARD if current treatment is not effective. For some patients, even after switching, disease control remains elusive. This analysis aims to quantify the frequency of, and identify factors associated with, bDMARD refractory disease. METHODS: Patients with RA starting first-line tumour necrosis factor inhibitor in the British Society for Rheumatology Biologics Register for RA from 2001 to 2014 were included. We defined patients as bDMARD refractory on the date they started their third class of bDMARD. Follow-up was censored at last follow-up date, 30 November 2016, or death, whichever came first. Switching patterns and stop reasons of bDMARDs were investigated. Cox regression identified baseline clinical factors associated with refractory disease. Multiple imputation of missing baseline data was used. RESULTS: 867 of 13 502 (6%) patients were bDMARD refractory; median time to third bDMARD class of 8 years. In the multivariable analysis, baseline factors associated with bDMARD refractory disease included patients registered more recently, women, younger age, shorter disease duration, higher patient global assessment, higher Health Assessment Questionnaire score, current smokers, obesity and greater social deprivation. CONCLUSIONS: This first national study has identified the frequency of bDMARD refractory disease to be at least 6% of patients who have ever received bDMARDs. As the choice of bDMARDs increases, patients are cycling through bDMARDs quicker. The aetiopathogenesis of bDMARD refractory disease requires further investigation. Focusing resources, such as nursing support, on these patients may help them achieve more stable, controlled disease.

Long-term persistence of TNF-inhibitor treatment in patients with psoriatic arthritis. Data from the British Society for Rheumatology Biologics Register.

BACKGROUND: Long-term effectiveness of tumour necrosis factor alpha inhibitors (TNFi) has mainly been explored in patients with rheumatoid arthritis (RA) and the data available on patients with psoriatic arthritis (PsA) includes limited follow-up. OBJECTIVE: Investigate long-term effectiveness of first TNFi in a PsA population by describing treatment persistence, identify factors associated with 5-year persistence and further investigate comparative long-term effectiveness of subsequent TNFi treatments through persistence to treatment. METHODS: Patients with a rheumatologist diagnosis of PsA receiving their first TNFi registered in the British Society for Rheumatology Biologics Register (BSRBR) (2002-2006) were included. Treatment at different time points was described and factors associated with 5-year treatment persistence were identified by logistic regression. Kaplan-Meier analysis was used to assess factors associated with persistence to first TNFi and subsequent TNFi treatments. RESULTS: At 5 years, 46.7% of patients were still on their initial TNFi treatment. Better 5 -year persistence was associated with male gender, use of etanercept or adalimumab rather than infliximab and absence of baseline comorbidity. Five-year persistence estimates (95% CI) of first, second and third TNFi were 53% (49% to 57%), 60% (43% to 57%) and 48% (36% to 59%), respectively. CONCLUSION: We found good long-term persistence of TNFi in this PsA population both for the first and subsequent TNFi treatments. The relationship between persistence and relevant clinical factors was not strong and demonstrates the difficulties in predicting outcome of TNFi treatment in PsA.

Serious infection risk after 1 year between patients with rheumatoid arthritis treated with rituximab or with a second TNFi after initial TNFi failure: results from The British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

Objectives: Both TNF inhibitors (TNFi) and rituximab (RTX), a B-cell depleting biologic, can disrupt the immune system in RA. RTX is licensed in Europe for use following TNFi failure. However, safety data on serious infections (SIs) are scarce for RTX in daily practice. This analysis aims to compare the risk of SIs in the first year after a switch to either TNFi or RTX in patients who have failed a first TNFi. Methods: This study included patients with RA registered with the British Society for Rheumatology Biologics Register (BSRBR-RA) who switched to either a second TNFi or RTX after failing a first TNFi. Patients were followed until first SI, treatment discontinuation, last recorded follow-up or the end of the first year after the switch, whichever came first. SI was defined as requiring hospitalization, intravenous antibiotics or resulting in death. The risk of first SI was compared between TNFi and RTX using Cox proportional hazard models adjusted using propensity scores using inverse probability of treatment weighting. Results: This analysis included 3419 TNFi and 1396 RTX patients contributing 2765 and 1224 person-years (pyrs), respectively. SI occurred in 164 (4.8%) TNFi and 81 (5.8%) RTX patients giving a crude rate of 59 and 66 SI/1000 pyrs, respectively. The adjusted hazard ratio for SI was 1.0 (95% CI: 0.7, 1.4). Conclusion: The risk of SIs was comparable over the first year of treatment between TNFi and RTX treatment in patients who had failed a single prior TNFi.

Mortality in patients with interstitial lung disease treated with rituximab or TNFi as a first biologic.

OBJECTIVES: Guidelines cautioned prescribing of tumour necrosis factor inhibitors (TNFi) to patients with rheumatoid arthritis and interstitial lung disease (RA-ILD) after reports of new or worsening of ILD. Less is known about outcomes among patients with RA-ILD who receive rituximab (RTX). This study compares mortality in patients with RA-ILD who received RTX or TNFi as their first biologic. METHODS: Participants with RA-ILD recruited to the British Society for Rheumatology Biologics Register for RA were included. Death rates were calculated and risk comparisons were made using Cox regression. Causes of death, including the frequency in which ILD was recorded on death certificates were examined. RESULTS: 43 patients on RTX and 309 on TNFi were included. RTX recipients had shorter disease duration and less disability. Death rates were 94.8 (95%CI: 74.4 to 118.7) and 53.0 (22.9 to 104.6) per 1000 person years, respectively. The adjusted mortality risk was halved in the RTX cohort, but the difference was not statistically significant (HR 0.53, 95% CI: 0.26 to 1.10). ILD was the underlying cause of death in 1 of 7 RTX deaths (14%) and 12 of 76 TNFi deaths (16%). CONCLUSIONS: Patients with RA-ILD who received RTX had lower mortality rates compared to TNFi. The absence of information on ILD severity or subtype prevents conclusions of which drug represents the best choice in patients with RA-ILD and active arthritis.

Relationship between exposure to tumour necrosis factor inhibitor therapy and incidence and severity of myocardial infarction in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of myocardial infarction (MI) compared with subjects without RA, with the increased risk driven potentially by inflammation. Tumour necrosis factor inhibitors (TNFi) may modulate the risk and severity of MI. We compared the risk and severity of MI in patients treated with TNFi with that in those receiving synthetic disease-modifying antirheumatic drugs (sDMARDs). METHODS: This analysis included patients with RA recruited from 2001 to 2009 to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis starting TNFi (etanercept/infliximab/adalimumab) and a biologic-naïve comparator cohort receiving sDMARD. All patients were followed via physician and patient questionnaires and national death register linkage. Additionally, all patients were linked to the Myocardial Ischaemia National Audit Project, a national registry of hospitalisations for MI. Patients were censored at first verified MI, death, 90 days following TNFi discontinuation, last physician follow-up or 20 April 2010, whichever came first. The risk of first MI was compared between cohorts using COX regression, adjusted with propensity score deciles (PD). MI phenotype and severity were compared using descriptive statistics. 6-month mortality post MI was compared using logistic regression. RESULTS: 252 verified first MIs were analysed: 58 in 3058 patients receiving sDMARD and 194 in 11 200 patients receiving TNFi (median follow-up per person 3.5 years and 5.3 years, respectively). The PD-adjusted HR of MI in TNFi referent to sDMARD was 0.61 (95% CI 0.41 to 0.89). No statistically significant differences in MI severity or mortality were observed between treatment groups. CONCLUSIONS: Patients with RA receiving TNFi had a decreased risk of MI compared with patients with RA receiving sDMARD therapy over the medium term. This might be attributed to a direct action of TNFi on the atherosclerotic process or better overall disease control.

Risk of lymphoma in patients exposed to antitumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma compared with the general population. There are concerns that tumour necrosis factor inhibitors (TNFi) may exacerbate this risk. However, since the excess risk of lymphoma in RA is related to the cumulative burden of inflammation, TNFi may conversely reduce the risk of lymphoma by decreasing the burden of inflammation. The aim of this study was to compare the risk of lymphoma in subjects with RA treated with TNFi with those treated with non-biological therapy. METHODS: Subjects diagnosed by a rheumatologist with RA enrolled in the British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA), a prospective cohort study, were followed until first lymphoma, death or until 30 November 2013. Rates of lymphoma in the TNFi and non-biological-treated cohorts were compared using Cox regression. RESULTS: 11 931 TNFi-treated patients were compared with 3367 biological-naive patients. 84 lymphomas (88 (95% CI 70 to 109) per 100 000 person-years) were reported in the TNFi cohort and 30 lymphomas (154 (95% CI 104 to 220)) in the biological-naive cohort. After adjusting for differences in baseline characteristics, there was no difference in the risk of lymphoma for the TNFi versus the biological-naive group: HR 1.00 (95% CI 0.56 to 1.80). No risk differences were observed for individual TNFi. CONCLUSIONS: In medium-term follow-up, there is no evidence that tumour necrosis factor inhibition influences the risk of lymphoma over the background risk in subjects with RA.

Use and effectiveness of tocilizumab among patients with rheumatoid arthritis: an observational study from the British Society for Rheumatology Biologics Register for rheumatoid arthritis.

The aims of the present study are to describe the characteristics of rheumatoid arthritis (RA) patients selected for tocilizumab (TCZ), compare the "real-world" effectiveness of TCZ and tumour necrosis factor inhibitors (TNFi) when used as a first biologic and assess the influence of past biologic exposure/concurrent methotrexate (MTX) therapy on post-TCZ treatment outcomes. The British Society for Rheumatology Biologics Register (BSRBR-RA) is a prospective cohort study following RA patients starting biologics in the UK. This includes patients starting TCZ as first or subsequent biologic, alongside biologic-naïve patients starting TNFi. Six-month disease activity and 1-year drug survival were compared between biologic-naïve patients starting TCZ versus TNFi and first-line versus subsequent TCZ users and TCZ users with MTX versus without using regression models adjusted by propensity score. Two hundred seventeen patients started TCZ, and 2419 started TNFi as first biologic. Seven hundred seventy-seven started TCZ after other biologics. First-line TCZ users had a higher prevalence of pulmonary fibrosis and cancer history than TNFi users. The first-line TCZ users were more likely to achieve DAS28 remission at 6 months than first-line TNFi, but other improvement markers were similar. The treatment response at 6 months was similar between subsequent-line TCZ users and first-line users after adjusting for baseline patient differences. Concurrent MTX use was not associated with treatment response in either first- or subsequent-line TCZ users. TCZ has been primarily used as subsequent-line biologic in the UK. When used as first line, the response appears similar to that observed in patients starting TNFi, suggesting that clinical response alone should not decide between initial biologic therapies.

Effectiveness and safety of TNF inhibitors in adults with juvenile idiopathic arthritis.

INTRODUCTION: Many children with juvenile idiopathic arthritis (JIA) continue to have active disease into adulthood. Adults with JIA are a heterogeneous group, and the effects of tumour necrosis factor inhibitor (TNFi) therapies are not well described. This analysis aims to describe treatment outcomes among patients with JIA starting TNFi for the first time in adulthood. METHODS: Patients with arthritis onset <16 years starting their first TNFi therapy were identified from the British Society of Rheumatology Biologics Register. Disease activity outcomes (using 28-joint Disease Activity Score (DAS28) and Health Assessment Questionnaire (HAQ)) are presented at 1 year after start of therapy according to disease pattern. Incidence rates (IR) of adverse events per 1000 person-years (pyrs) were calculated. Outcomes in patients with polyarticular JIA were compared with a cohort (weighted for age and gender) of patients with rheumatoid arthritis (RA). RESULTS: In 443 adults with JIA starting a first TNFi, disease activity over 1 year improved across all measures. There were 58 first serious infections (IR 22.3/1000 pyrs); 4 cardiovascular events (IR 1.4/1000 pyrs); 11 uveitis events (IR 4.0/1000 pyrs) and 16 malignancies (IR 3.9/1000 pyrs). Compared with the weighted RA cohort, disease activity improvement was similar; malignancy rates were lower and uveitis rates much higher. While crude IR were similar, JIA patients had a lower risk of serious infection (HR 0.5 (95% CI 0.3 to 0.9)). CONCLUSIONS: This is the largest study to describe disease activity and safety outcomes in adults with JIA receiving TNFi. Disease activity improved after 1 year in all disease patterns, suggesting TNFi is an effective therapy in this population.

The incidence of cancer in patients with rheumatoid arthritis and a prior malignancy who receive TNF inhibitors or rituximab: results from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis.

OBJECTIVE: To explore the influence of TNF inhibitor (TNFi) therapy and rituximab (RTX) upon the incidence of cancer in patients with RA and prior malignancy. METHODS: The study population comprised RA subjects with a prior malignancy reported to the UK national cancer registers, recruited to the British Society for Rheumatology Biologics Register from 2001 to 2013. We compared rates of first incident malignancy in a TNFi cohort, RTX cohort and synthetic DMARDs (sDMARD) cohort. RESULTS: We identified 425 patients with a prior malignancy from 18 000 RA patients in the study. Of these, 101 patients developed a new malignancy. The rates of incident malignancy were 33.3 events/1000 person-years (py) in the TNFi cohort, 24.7 events/1000 py in the RTX cohort and 53.8 events/1000 py in the sDMARD cohort. The age- and gender-adjusted hazard ratio was 0.55 (95% CI: 0.35, 0.86) for the TNFi cohort and 0.43 (95% CI: 0.10, 1.80) for the RTX cohort in comparison with the sDMARDs cohort. The 17.0% of patients in the sDMARDs cohort had a recurrence of the same cancer in comparison with the 12.8% and the 4.3% in the TNFi and RTX cohorts, respectively. CONCLUSIONS: Although numbers are still low, it seems that patients with RA and prior malignancy selected to receive either a TNFi or RTX in the UK do not have an increased risk of future incident malignancy.

Association Between Ischemic Stroke and Tumor Necrosis Factor Inhibitor Therapy in Patients With Rheumatoid Arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at an increased risk of ischemic stroke. Tumor necrosis factor inhibitors (TNFi) may influence risk and mortality after ischemic stroke by reducing inflammation. This study was undertaken to examine the association of TNFi with the risk of incident ischemic stroke and with 30-day and 1-year mortality after ischemic stroke. METHODS: Patients with RA starting therapy with TNFi and a biologics-naive comparator group treated with synthetic disease-modifying antirheumatic drugs (DMARDs) only were recruited to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis from 2001 to 2009. Patients were followed up via clinical and patient questionnaires as well as the national death register. Incident strokes were classified as ischemic if brain imaging reports suggested ischemia or if ischemic stroke was reported as the underlying cause of death on a death certificate. Patients with a previous stroke were excluded. Risk of ischemic stroke was compared between patients receiving synthetic DMARDs only and those ever-exposed to TNFi using a Cox proportional hazards regression model adjusted for potential confounders. Mortality after ischemic stroke was compared between synthetic DMARD-treated patients and TNFi-treated patients using logistic regression, adjusted for age and sex. RESULTS: To April 2010, 127 verified incident ischemic strokes (21 in 3,271 synthetic DMARD-treated patients and 106 in 11,642 TNFi-treated patients) occurred during 11,973 and 61,226 person-years of observation, respectively (incidence rate 175 versus 173 per 100,000 person-years). After adjustment for confounders, there was no association between ever-exposure to TNFi and ischemic stroke (hazard ratio 0.99 [95% confidence interval (95% CI) 0.54-1.81]). Mortality 30 days or 1 year after ischemic stroke was not associated with concurrent TNFi exposure (odds ratio 0.18 [95% CI 0.03-1.21] and 0.60 [95% CI 0.16-2.28], respectively). CONCLUSION: Exposure to TNFi does not appear to influence the occurrence of ischemic stroke in the medium term in patients with RA. The impact on mortality after ischemic stroke remains inconclusive.

Risk of solid cancer in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk of certain solid cancers, in particular lung cancer, compared to the general population. Treatment with tumour necrosis factor (TNF) inhibitors (TNFi) may further enhance this risk. OBJECTIVES: To compare the risk of solid cancer in patients with RA treated with TNFi to that in patients treated with non-biologic (synthetic) disease modifying antirheumatic drugs (sDMARDs). METHODS: Patients with a physician diagnosis of RA enrolled in the British Society for Rheumatology Biologics Register, a national prospective cohort study established in 2001 to monitor the long-term safety of TNFi, were followed via record linkage with the national cancer registries until first solid cancer, death, for 5 years, or until 2011. Rates of solid cancers in 11 767 patients without prior cancer who received TNFi were compared to those in 3249 patients without prior cancer treated with sDMARDs. RESULTS: 427 solid cancers were reported in 52 549 patient-years follow-up for the TNFi group (81 (95% CI 74 to 89) per 10 000 patient-years) and 136 cancers were reported in 11 672 patient-years in the sDMARD cohort (117 (95% CI 98 to 138) per 10 000 patient-years). After adjusting for differences in baseline characteristics there was no difference in risk of solid cancer for TNFi compared to sDMARD treated patients: HR 0.83 (95% CI 0.64 to 1.07). There was no difference in the relative risk of cancer for any of the individual TNFi drugs. CONCLUSIONS: The addition of TNFi to sDMARD does not alter the risk of cancer in RA patients selected for TNFi in the UK.

The risk of gastrointestinal perforations in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the BSRBR-RA.

OBJECTIVES: To evaluate the risk of gastrointestinal perforation (GIP) in subjects with rheumatoid arthritis (RA) treated with antitumour necrosis factor (anti-TNF) therapy compared with non-biological disease-modifying antirheumatic drugs (nbDMARDs). METHODS: Using data from the British Society for Rheumatology Biologics Register, we compared the incidence of GIPs between 11 881 anti-TNF-treated and 3393 nbDMARD-treated RA patients using Cox regression modelling. Hazard ratios (HRs) with confidence intervals (CI) were calculated. Adjustment was made for potential confounders including current steroid use. The study covered the time period between 2001 and 2011. RESULTS: There were 42 (upper 20, lower 22) GI perforations: five in the nbDMARD cohort and 37 in the anti-TNF cohort. After adjustment, treatment with TNF antagonists was associated with an HR of 1.6 (95% CI 0.4 to 6.0) for all GIPs, 2.7 (95% CI 0.4 to 18.1) for lower GIPs and 0.9 (95% CI 0.1 to 5.8) for upper GIPs. Current use of steroids was the single most important predictor of GI perforation with an adjusted HR of 2.9 (95% CI 1.5 to 5.4), but this risk was confined to lower GIPs (HR 8.0, 95% CI 2.6 to 24.1). CONCLUSIONS: We have not found a statistically significant association between anti-TNF treatment and the risk of GIP.