I.M. Visman

Ankylosing spondylitis: a risk factor for myocardial infarction?

Objective To ascertain the prevalence of myocardial infarction (MI) in ankylosing spondylitis (AS) relative to that in the general population. Methods A questionnaire was sent to 593 patients with AS, aged between 50 and 75 years and registered at the Jan van Breemen Institute or VU University Medical Centre. A total of 383 (65%) patients with AS returned their questionnaire that covered the primary outcome, (non-fatal) MI. The prevalence of MI was calculated with data from the general population provided by Netherlands Information Network of General Practice databases as reference. Results The overall prevalence for MI was 4.4% in patients with AS versus 1.2% in the general population, resulting in an age- and gender-adjusted odds ratio of 3.1 (95% CI 1.9 to 5.1) for patients with AS. When non-responders (35%) were considered as non-MI the odds ratio decreased to 1.9 (95% CI 1.2 to 3.2). Conclusions These observations indicate that the prevalence of MI is increased in patients with AS.

Decreasing incidence of symptomatic gastrointestinal ulcers and ulcer complications in patients with rheumatoid arthritis

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) frequently cause gastrointestinal (GI) ulcers and complications of ulcers. In 1997 in Amsterdam, the incidence of symptomatic GI events was 2.1% (95% CI 1.0–3.1) in patients with rheumatoid arthritis (RA). We conducted a new prospective, observational study on the symptomatic GI events in our outpatient clinics, and compared the data to a previous study conducted by our group. Over the same time period, a decline of GI events over the last decade was reported for US patients. Methods: In 2003, three questionnaires were sent to all RA patients in Amsterdam at 4-month intervals, addressing medication use, dyspepsia, and symptomatic GI events in the previous 4 months. Results: The incidence of GI events in high-risk patients, defined as age ⩾60 and/or history of GI event) using NSAIDs or cyclo-oxygenase 2 specific inhibitors (COXIBs) was 1.2% (95% CI 0.2–2.3), which appears to be substantially lower than the 2.1% observed in 1997; however this difference did not reach statistical significance (p = 0.3). In 64% (95% CI 61–68) of the high-risk patients, acid-suppressive drugs (ie, proton pump inhibitors, prostaglandin analogues or high dose H2 antagonists) were used. In 1997 this percentage was significantly lower at 49% (45–52; p<0.001). The compliance to the Dutch guidelines for prevention of NSAID-related gastropathy was almost 75%, with 64% of the patients using acid-suppressive drugs and 11% using COXIBs. Conclusion: The present study reveals a decline of NSAID-induced gastrointestinal events, which is similar to the results observed in the US. This is most likely due to a more strict adherence to guidelines for prevention of NSAID gastropathy, and better treatment of rheumatoid arthritis.

Prevalence of cardiovascular diseases in psoriatic arthritis resembles that of rheumatoid arthritis

The increased risk for cardiovascular disease (CVD) in rheumatoid arthritis (RA) is well known and inflammation appears to play a pivotal aetiological role. There is now substantial interest in whether or not psoriatic arthritis (PsA) is also associated with an enhanced cardiovascular (CV) risk. However, data on CVD in PsA is limited.1,–,3 The aim of this comparative study was to determine the prevalence of non-fatal CVD in patients with PsA compared with patients with RA and to investigate the risk factors of CVD in PsA. In 2008 a CV questionnaire was sent to all 753 patients with PsA aged 50–75 years registered at our centre.4 As a comparator group, data from 353 randomly selected patients with RA aged 50–75 years (the CARdiovascular research and RhEumatoid arthritis study) were …

Adalimumab significantly reduces the recurrence rate of anterior uveitis in patients with ankylosing spondylitis.

Objective. To investigate whether use of adalimumab decreases the frequency of attacks of anterior uveitis (AU) in patients with ankylosing spondylitis (AS). Methods. Consecutive patients with AS, visiting an outpatient clinic and treated for at least 12 weeks with adalimumab, were enrolled. The number of attacks of AU in the year before start and during treatment were assessed by patient history and ophthalmological controls. Results. In the 77 patients a total of 52 AU attacks occurred in the year before baseline (68 attacks per 100 patient-yrs), whereas during adalimumab treatment 19 attacks were seen (14 per 100 patient-yrs; reduction rate 80%). Twenty-six patients with AU in the year before start of adalimumab treatment had recurrent attacks, with a median number of 2.0 AU attacks per year [interquartile range (IQR) 1.00–3.00], whereas during treatment this decreased to 10 patients with a median number of 0.56 attacks per year (IQR 0.30–0.75). Hence, the number of attacks per year decreased by 72% (p = 0.000). Conclusion. In patients with AS, a significant reduction in the number of AU attacks, as well as in the number of attacks per patient, was observed during adalimumab treatment.

High incidence of cardiovascular events in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is associated with higher risk for cardiovascular disease (CVD) in comparison with the general population.1 Traditional cardiovascular (CV) risk factors only partially explain the higher risk for CVD.2 There is increasing evidence that inflammation explains the enhanced CV risk in RA, as inflammation has a pivotal role in the development of atherosclerotic disease and this might be the link between increased atherosclerotic CVD and RA.3 Other RA-related factors might be undertreatment of CV comorbidity,1 and the use of non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclo-oxygenase 2 inhibitors.4,5 The objective of this prospective observational study was to determine the incidence of CV events in patients with RA in comparison to the general Dutch population, where the incidence of CV events is …

Muscle wasting in male TNF-α blocker naïve ankylosing spondylitis patients: a comparison of gender differences in body composition

Objective To assess gender differences in body composition (BC) in a cohort of AS patients naïve to TNF-α blockers. Methods Patients included fulfilled the Modified New York criteria for AS. Demographic information and disease activity measures (ASDAS and BASDAI) were reported. BC was measured by whole body DXA. Body fat percentage (BF%), fat mass index (FMI), fat free mass index (FFMI) and android/gynoid fat ratio were reported and compared between men and women and with the reference population (percentiles). Results Seventy consecutive patients were included; 60% were men. Demographic variables were similar, except for dyslipidaemia (57.1% of men; 14.3% of women). Women had significantly more fat (BF%, FMI), and less muscle (FFMI) than men, but below the median of the reference population. Male AS patients had a markedly low FFMI (31.7th percentile) compared with the reference population. In the whole group, after multivariate analysis, an ASDAS CRP >3.5 was related to lower fat free mass content. In men, a significant relationship between having a high disease activity (ASDAS, BASDAI) and lower BF% or FMI percentile was found, but in women it was the opposite. Conclusion Muscle wasting, measured as low FFMI compared with the reference population, was found in male TNF-α blocker naïve AS patients, especially in those with active disease. Women had higher volumes of body fat than men, but near the median of the reference population. The relationships between fat content and disease activity support the complex association between adipose tissue and inflammation.

Fat Mass Lowers the Response to Tumor Necrosis Factor-α Blockers in Patients with Ankylosing Spondylitis

Objective. Our main objective was to assess the relationship between body composition (BC) and response to tumor necrosis factor-α (TNF-α) blocker treatment in patients with ankylosing spondylitis (AS). Our secondary objective was to evaluate the change of BC after treatment, accounting for sex and age. Methods. All included patients fulfilled the modified New York criteria for AS and were naive to TNF-α blocker. They were followed for at least 6 months after the start of etanercept or adalimumab. The Ankylosing Spondylitis Disease Activity Score containing C-reactive protein (ASDAS-CRP) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were reported. BC was assessed by whole body dual-energy X-ray absorptiometry. Body fat percentage (BF%), fat mass index (FMI), and fat free mass index (FFMI) were reported as absolute values and as percentiles. Results. Forty-one patients were included (61% men). The median followup was 14.3 months (interquartile range 8.4–19.4). After multivariate regression analysis, more fat at baseline (BF%, FMI, or FMI percentile) was significantly related with a lower chance of achieving a clinically important improvement of the ASDAS-CRP or BASDAI after treatment. The body composition did not change significantly after treatment, but there was a trend toward muscle recovery in men (FFMI change from 34.0th to 37.4th percentile). Conclusion. Higher body fat content at baseline was independently associated with a worse response to treatment with TNF-α blockers, measured by ASDAS-CRP and BASDAI change, and might contribute to the lower response rates in female patients. Also, there is a trend toward muscle mass recovery in male patients after treatment.

THU0391 Female gender is associated with a poorer response to tnf inhibitors in ankylosing spondylitis

Background Limited data are available on the influence of gender and lifestyle factors, such as smoking, alcohol consumption and Body Mass Index (BMI) on disease activity and response to TNF inhibitors (TNFi) in ankylosing spondylitis (AS). Objectives This study aimed to determine whether these factors influence age at diagnosis, disease activity and response to TNFi. Methods In a prospective study, clinical data (age, gender, C-reactive protein, Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Score (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI), smoking, alcohol consumption and BMI) were collected in AS patients from a observational cohort, who started or switched treatment with TNFi. Data were collected at baseline and after 6, 12 and 24 months. Independent T-tests and linear regression analyses were performed to assess the influence of gender and lifestyle factors on age at diagnosis and disease activity. Results In total, 312 consecutive AS patients, 34% female, were included with a mean follow-up of 18.9 months. Most patients (172, 55%) showed significant improvement after start of TNFi of whom 86 patients (28%) had a clinically important (ASDAS decrease >1.1) and 86 (26.9%) a major clinical improvement (ASDAS decrease >2.2). BMI was significantly correlated with age at diagnosis (p=0.016; 95% CI: 0.07 – 0.65): an increase of BMI with three points delayed the AS diagnosis with one year. At baseline, smoking and gender were not correlated with the ASDAS, but BASDAI and BASMI were both inversely related to BMI. Male gender was significantly associated with a higher chance at clinical response (improvement of the BASDAI with 50% or a 2 point decrease) to TNFi (p=0.041). At one year follow-up the clinical improvement of males versus females was respectively 62% vs. 43% and at two year follow-up 59% vs. 46%. Males also showed a significantly higher ASDAS improvement after one year of follow-up compared to females (p=0.015). Conclusions Significantly less females had a clinical response compared to males after one and two years of TNFi treatment. A higher BMI not only prolonged the time to AS diagnosis up to one year, but also negatively influenced the BASDAI and BASMI scores. Female gender and high body weight should be taken into consideration when the efficacy of TNFi is assessed, by stratifying for these factors in the analysis. Disclosure of Interest None declared

Effect of the Application of Trial Inclusion Criteria on the Efficacy of Adalimumab Therapy in a Rheumatoid Arthritis Cohort

Objective. To evaluate the influence of inclusion criteria used in rheumatoid arthritis (RA) trials with adalimumab on clinical outcome and response. Methods. The different inclusion criteria of published trials of adalimumab in RA were separately applied to a large prospective cohort of patients with RA treated with adalimumab (AdRA cohort), thereby mimicking patient selection for a clinical trial. Clinical response and outcome in the resulting 11 projection groups were compared using the 28-joint Disease Activity Score (DAS28) and time-averaged DAS28 as outcome measures of efficacy. Results. Thirteen trials (n = 54–799) with 11 different sets of entry criteria were identified, resulting in 11 projection groups (n = 22–168). The DAS28 at baseline was similar in the original trial and each projection group based on this trial (5.1–6.4, total AdRA cohort 5.1). After 28 weeks, the efficacy varied substantially among the 11 projected groups (change from baseline DAS28: −1.65 to −2.65, time-averaged DAS28 3.67–4.53). Expressed as outcome (DAS28 at 28 weeks), the efficacy was much more similar for almost all projection groups (3.5–4.0) and thus appeared to be mostly independent of disease activity at baseline. Conclusion. We observed that different inclusion criteria for clinical trials can have a marked effect on the expected response, i.e., improvement from baseline. A novel finding is that final disease activity appeared much less dependent on initial disease activity. Our study suggests that for daily practice, one can assume that adalimumab treatment will on average result in a DAS28 between 3.5 and 4.0 after 28 weeks of treatment, regardless of baseline disease activity.

AB0837 The effect of anti-tnf on renal function in patients with ankylosing spondylitis: a prospective cohort study

Background Impaired renal function is common in patients with ankylosing spondylitis (AS) and patients also have an increased risk of cardiovascular disease (CVD). Previous studies showed that biologicals, such as anti-Tumour Necrosis Factor (anti-TNF) reduce CVD in patients with inflammatory rheumatic disease. Impaired renal function is a known predictor of CVD (also elevated in AS). We postulated that the favourable cardiovascular effect of anti-TNF might be mediated by improving renal function. However, data about the effect of biologicals on renal function in patients with AS are lacking. Objectives To assess the effect of anti-TNF on renal function in patients with AS. Methods Biological-naïve consecutive AS patients treated with etanercept or adalimumab were prospectively followed from 2005 to 2014. Renal function was determined by calculation of the estimated Glomerular Filtration Rate (eGFR), which was estimated with the abbreviated Modification of Diet in Renal Disease (MDRD) formula. Patients were divided into two groups: patients with normal renal function at baseline and patients with impaired renal function at baseline, to investigate whether the effect is different for these groups. Normal renal function was defined by eGFR ≥90 mL/min/1.73 m2 at baseline and impaired renal function was defined by eGFR <90 mL/min/1.73 m2 at baseline. The effect of anti-TNF on eGFR was analysed using mixed model analysis. Results 211 AS patients were followed for a median of 156 (36 – 286) weeks. 153 patients had normal renal function and 58 had impaired renal function at baseline. In patients with normal renal function at baseline eGFR decreased significantly over time (β=−0.041, p=0.001), although this association did not remain significant after adjustment for disease activity (β=−0.015, p=0.212). Patients with impaired renal function at baseline did not have a significant change in eGFR over time (β=0.022, p=0.087) and this association remained not significant after adjustment for alcohol consumption, BMI, disease duration and disease activity (β=0.008, p=0.593). The change in eGFR on average over time after starting anti-TNF in AS patients with normal and impaired kidney function are presented in figure 1.Abstract AB0837 – Figure 1 Conclusions This study demonstrates that anti-TNF is not associated with renal function in AS patients, which means that use of anti-TNF is safe concerning renal function in patients with AS. From our results it seems that the effect of anti-TNF on CVD in AS patients is not mediated by an effect on renal function. Disclosure of Interest None declared