Cecilia Lourdudoss

Mycophenolate mofetil in the treatment of SLE and systemic vasculitis: experience at a single university center

Mycophenolate mofetil (MMF) is used off-label for systemic lupus erythematosus (SLE) and systemic vasculitis. The study aim was to investigate clinical use and treatment results with MMF in patients with SLE and systemic vasculitis. This study included patients with SLE or systemic vasculitis with ongoing or previous MMF treatment. Data on treatment outcome were obtained through medical record reviews. A total of 135 of 648 (21%) patients with SLE and 43 of 455 (9%) patients with systemic vasculitis had ongoing or previous MMF treatment. Among SLE patients, the most common organ manifestation at baseline (treatment start) was renal involvement (50%). Most of the systemic vasculitis patients had Wegener’s granulomatosis (GPA) (65%). Median dose of MMF was 2000 mg/day. Glucocorticoid (GC) doses were significantly reduced during MMF treatment from 21.7 mg/day at baseline to 8.3 mg/day at 12 months (p < 0.05). Forty-six percent of the patients were good responders after 12 months. The most common adverse events (AES) leading to discontinuation were side effects in the gastrointestinal tract (40%) and general side effects (30%). “Survival-on-drug” analysis suggested that 40% of the patients remained on long-term MMF treatment. In conclusion, MMF was used in 21% of the SLE patients and 9% of the systemic vasculitis patients. MMF appeared to be effective with a reasonable survival-on-drug and a GC-sparing effect.

Dietary Intake of Polyunsaturated Fatty Acids and Pain in spite of Inflammatory Control among Methotrexate Treated Early Rheumatoid Arthritis Patients

To investigate potential associations between dietary intake of polyunsaturated fatty acids (FAs) and pain patterns in early rheumatoid arthritis (RA) patients after 3 months of methotrexate (MTX) treatment.

Obesity is a strong predictor of worse clinical outcomes and treatment responses in early rheumatoid arthritis: results from the SWEFOT trial

Objectives The aim of this paper was to analyse the impact of obesity, in addition to known predictors, on disease outcome in early rheumatoid arthritis (RA). Methods Body mass index (BMI) was available in 260 patients from the Swedish pharmacotherapy trial (SWEFOT). Differences in disease activity (DAS28), functional impairment (HAQ), pain (Visual Analogue Scale, VAS-pain) and radiographic damage were evaluated over 24 months between BMI categories (obese BMI >30, n=43; overweight BMI=25–29.9, n=74; normal BMI <25, n=143) using non-parametric testing. Predictors of European League Against Rheumatism non-remission (DAS28 ≥2.6) at 24 months of follow-up were evaluated using binary univariate and multivariate logistic regression. Results Obesity at baseline was associated with worse continuous-scale clinical outcomes over 24 months (DAS28, HAQ and VAS-pain at last visit: obese vs normal: p<0.001; obese vs overweight: p<0.05). Furthermore, obese patients compared with non-obese patients had significantly greater odds of non-remission at 24 months (adjusted OR (aOR) 5.2; 95% CI 1.8 to 15.2). Other independent predictors were female sex (aOR 2.6; 95% CI 1.1 to 5.8), current smoking (aOR 2.6; 95% CI 1.1 to 6.3) and HAQ (per-unit increase, aOR 1.9; 95% CI 1.1 to 3.4). The pattern was similar among seropositive and seronegative patients; and in the subgroups of methotrexate responders and patients randomised at 3 months to add-on of sulfasalazine+hydroxychloroquine, although not significant with add-on of infliximab. Obesity had no independent association to radiographic progression. Conclusions In this early RA trial reflecting today’s standard treatment, obesity, in addition to sex, smoking and functional impairment strongly lowered the chance of attaining good clinical outcomes, including remission, today’s treatment goal. This highlights the importance of considering lifestyle modification as one of the cornerstones of RA care. Trial registration number NCT00764725; Post-results. WHO database at the Karolinska University Hospital: CT20080004.

Are dietary vitamin D, omega-3 fatty acids and folate associated with treatment results in patients with early rheumatoid arthritis? Data from a Swedish population-based prospective study

Background Dietary intake of vitamin D and omega-3 fatty acids (FA) may be associated with superior response to antirheumatic treatments. In addition, dietary folate intake may be associated with worse response to methotrexate (MTX). The aim of this study was to investigate the association between dietary vitamin D, omega-3 FA, folate and treatment results of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). Methods This prospective study was based on data from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, and included 727 patients with early RA from 10 hospitals in Sweden. Data on dietary vitamin D, omega-3 FA and folate intake based on food frequency questionnaires were linked with data on European League Against Rheumatism (EULAR) response after 3 months of DMARD treatment. Associations between vitamin D, omega-3 FA, folate and EULAR response were analysed with logistic regression adjusted for potential confounders. Results The majority of patients (89.9%) were initially treated with MTX monotherapy and more than half (56.9%) with glucocorticoids. Vitamin D and omega-3 FA were associated with good EULAR response (OR 1.80 (95% CI 1.14 to 2.83) and OR 1.60 (95% CI 1.02 to 2.53), respectively). Folate was not significantly associated with EULAR response (OR 1.20 (95% CI 0.75 to 1.91)). Similar results were seen in a subgroup of patients who were initially treated with MTX monotherapy at baseline. Conclusions Higher intake of dietary vitamin D and omega-3 FA during the year preceding DMARD initiation may be associated with better treatment results in patients with early RA. Dietary folate intake was not associated with worse or better response to treatment, especially to MTX. Our results suggest that some nutrients may be associated with enhanced treatment results of DMARDs.

The association between diet and glucocorticoid treatment in patients with SLE.

Background Some studies suggest that the risk for and severity of systemic lupus erythematosus (SLE) can be modified by certain nutrients. The aim of this study was to investigate the association between diet and glucocorticoid (GC) treatment, as a proxy for disease activity, in patients with SLE. Methods We included 111 patients with SLE from the SLE Vascular Impact Cohort (SLEVIC). Dietary data were linked with data on GC treatment during a 2-year period. The association between diet and GC treatment was analysed with logistic regression. GC treatment and unchanged/increased doses were considered a proxy for active SLE. Results During the 2-year period, 54 patients (48.6%) had continued GC treatment. Dietary vitamin D was associated with GC treatment (OR=2.70–2.85 (95% CI 1.00 to 8.11)), whereas alcohol was inversely associated with GC treatment (OR=0.28–0.39 (95% CI 0.10 to 98)). Beta-carotene, fatty acid C18:2 and vitamin B6 were inversely associated with unchanged/increased GC dose (OR=0.29–0.30 (95% CI 0.10 to 0.90)). Finally, total energy intake was associated with GC doses >5.0 mg/day and >7.5 mg/day, explaining a direct association between 35 nutrients and higher GC dose levels (OR=2.98–23.82 (95% CI 1.01 to 203.88)). Discussion Dietary vitamin D did not protect against lupus activity. Beta-carotene, fatty acid C18:2 and vitamin B6 may protect against increased GC dose. The inverse association between alcohol intake and GC treatment/lupus activity may provide a partial explanation for the link between moderate alcohol intake and reduced risk of SLE. The association between higher dietary intake and higher GC dose levels indicated GCs influence on increasing appetite.

Dietary micronutrient intake and atherosclerosis in systemic lupus erythematosus

Objective The aim of this study was to investigate the role of dietary micronutrient intake in systemic lupus erythematosus (SLE). Methods This study included 111 SLE patients and 118 age and gender-matched controls. Data on diet (food frequency questionnaires) were linked with data on Systemic Lupus Activity Measure, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and carotid atherosclerotic/echolucent plaque (B-mode ultrasound). Dietary micronutrient intake were compared between SLE patients and controls and in relation to lupus activity and atherosclerosis in SLE. Associations between micronutrient intake and plaque were analyzed through logistic regression, adjusted for potential confounders. Results Micronutrient intake did not differ between patients and controls, and between lower and higher lupus activity, apart from the fact that phosphorus was associated with SLEDAI > 6. In SLE patients, some micronutrients were associated with atherosclerotic plaque, left side. Lower intake of riboflavin and phosphorus was associated with atherosclerotic plaque, left side (odds ratio (OR) 3.06, 95% confidence interval (CI) 1.12–8.40 and OR 4.36, 95% CI 1.53–12.39, respectively). Higher intake of selenium and thiamin was inversely associated with atherosclerotic plaque, left side (OR 0.28, 95% CI 0.09–0.89 and OR 0.26, 95% CI 0.08–0.80, respectively). In addition, higher intake of thiamin was inversely associated with echolucent plaque, left side (OR 0.22, 95% CI 0.06–0.84). Lower intake of folate was inversely associated with bilateral echolucent plaque (OR 0.36, 95% CI 0.13–0.99). Conclusions SLE patients did not have different dietary micronutrient intake compared to controls. Phosphorus was associated with lupus activity. Riboflavin, phosphorus, selenium and thiamin were inversely associated with atherosclerotic plaque, left side in SLE patients, but not in controls. Dietary micronutrients may play a role in atherosclerosis in SLE.

Long-Term Dietary Changes after Diagnosis of Rheumatoid Arthritis in Swedish Women: Data from a Population-Based Cohort

Objective To investigate long-term dietary changes after rheumatoid arthritis (RA) diagnosis in Swedish women, compared to women without RA. Methods This study included 21,602 women from the Swedish Mammography Cohort (SMC), who completed dietary questionnaires in 1997 and 2009. Between 1997 and 2009, 191 women were diagnosed with RA. Dietary changes after RA diagnosis were analyzed based on intake of 82 food items. Statistical analysis included linear mixed models. Results Women with RA, compared to women without RA, had significantly lower intake (mean servings per week) of animal products such as black pudding, egg, kidney, and liver paste (2.94±2.73 versus 2.45±1.82, p=0.010) and dairy products (35.14±20.02 versus 28.42±16.10, p=0.040) in 1997 and of cereals and grains (31.01±15.54 versus 28.00±14.98, p=0.009) in 2009. However, multivariable adjusted changes in dietary intake from 1997 to 2009 did not show any significant difference in intake. Nevertheless, women without RA increased their intake of whole wheat bread, wheat/oat bran, and rice more than women with RA. Conclusion Women who had been diagnosed with RA had similar dietary patterns over time as the general population; these women did not remarkably change their diet over time due to their disease. Dietary recommendations for RA patients are needed.

FRI0062 Obesity Is Associated with Worse Clinical Outcomes Yet Limited Radiographic Progression in Early Rheumatoid Arthritis: Table 1.

Background In RA, being overweight or obese has previously been shown to be associated with worse clinical outcomes (1, 2), yet also less radiographic damage (2, 3). Objectives To confirm if body mass index (BMI) is associated with worse clinical disease activity or inversely associated with radiographic outcomes in early RA. Methods BMI, categorized as normal (<25, n=141), overweight (25–29.9, n=74), and obese (≥30, n=43), was available in 258 patients who were enrolled in the Swedish pharmacotherapy (SWEFOT) trial. After initial methotrexate for 3 months, non-responders were randomized to triple therapy or anti-TNF therapy, while responders continued on methotrexate. Disease activity (DAS28), functional impairment (HAQ), VAS-pain, and radiographic damage (Sharp van der Heijde score, SHS) were evaluated regularly. Here, results are shown at 24 months of follow-up. Results Treatment allocation and baseline outcome measures did not differ across the BMI categories. In a dose-response manner, higher BMI at baseline was associated with worse clinical outcomes over 24 months (DAS28, HAQ, and VAS-pain) (Table). Patients with normal (58%) or overweight (50%) BMI had a proportionally greater chance of attaining 24-month clinical remission (DAS28<2.6) than obese patients (23.1%) (OR 3.2 [95% CI 1.6–6.3], p<0.001; OR 2.2 [95% CI 1.2–4.1], p=0.007, respectively). Among absolute radiographic scores, no significant differences were observed, yet radiographic progression (ΔSHS≥1, baseline-24 months) was halted more frequently (56.3%) among obese patients than normal/overweight patients combined (37.6%) (OR 1.9 [95% CI 1.0–3.6], p=0.049) (obese vs. normal (40%), OR 1.7 [95% CI 0.9–3.1], p=0.101; obese vs. overweight (32.7%), OR 1.8 [95% CI 1.1–3.2], p=0.032).Table 1. Outcome measures after 24 months of disease-modifying antirheumatic agents Outcomes [Medians (IQR)] Normal (n=141) Overweight (n=74) Obese (n=43) P valuea DAS28 2.4 (1.7, 3.4)* 2.6 (2.2, 3.8)† 3.2 (2.8, 4.8)†* p<0.001 HAQ 0.3 (0.0, 0.8)* 0.5 (0.0, 1.0)† 0.8 (0.4, 1.3)†* p<0.001 VAS-pain 18.5 (6.0, 35.0)* 25.0 (8.0, 47.0)† 39.0 (22.0, 61.0)†* p<0.001 ESR 10.0 (6.0, 18.0)* 13.5 (8.0, 23.0) 18.0 (11.0, 26.0)* p=0.008 SHS 7.0 (2.0, 16.3) 6.5 (2.0, 14.0) 5.0 (0.8, 13.0) p=0.519 aKruskal-Wallis test (individual comparisons: Mann-Whitney U test; post-hoc comparisons: Dunn-Bonferroni (DB) correction). †Overweight vs. Obese: DAS28, p=0.012 (DB, p=0.020; adjusted, p=0.060); HAQ, p=0.030 (DB, p=0.021; adjusted. p=0.062); VAS Pain, p=0.025 (DB, p=0.023, adjusted: p=0.069). *Normal vs. Obese: Mann-Whitney or DB + adjustment, p<0.001 (erythrocyte sedimentation rate (ESR): p=0.003 (DB, p=0.003, adjusted: p=0.009)). Conclusions Obesity at diagnosis was found to be a strong predictor of worse long-term clinical outcomes in early RA – including disease activity, functional impairment, and pain; thus confirming previous findings. Nonetheless – as has also been previously shown – obesity was associated with a better chance of halting radiographic progression. References Sandberg ME, et al. Ann Rheum Dis. 2014 Nov;73(11):2029–33; Vidal C, et al. J Rheumatol. 2015 Dec;42(12):2261–9; Baker JF, et al. Ann Rheum Dis. 2014 Nov;73(11):1923–8 Disclosure of Interest A. Levitsky: None declared, S. Saevarsdottir: None declared, K. Brismar: None declared, K. Hambardzumyan: None declared, C. Lourdudoss: None declared, R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, Pfizer, Roche, and UCB, Consultant for: AbbVie, Biotest, BMS, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, and Vertex

SAT0017 Dietary Nutrients and Carotid Arteriosclerosis in SLE Patients

Background The prevalence of atherosclerosis is increased in SLE. Disease-specific and treatment-related factors have been implicated. We hypothesized that, in addition, diet may play an important role. However, relatively little is known about dietary habits in patients with SLE. Objectives The aim of this study was to investigate the dietary nutrient levels in SLE patients with and without carotid atherosclerosis. Methods This study included 111 SLE patients from the SLE vascular impact cohort (SLEVIC) study, Karolinska university hospital, Stockholm, Sweden. Data on diet were linked with data on unilateral and bilateral plaque. Dietary data were based on food frequency questionnaires. Data on plaque were scored as absence or presence of unilateral and bilateral plaque that were detected by B-mode ultrasound. Daily mean intake of dietary nutrients was compared between patients a) with and without bilateral plaque; b) with and without plaque in the left carotid. Data on plaque was adjusted for age and low density lipoprotein (LDL) levels through logistic regression. Results The results are shown in the table. Significant differences were found in the mean intake of several nutrients between patients with and without bilateral plaque. Overall, patients with carotid plaques had lower caloric intake of macronutrients and lower intake of various B vitamins and some other micronutrients. However, the dietary intake of fiber and of fatty acids C20:5 and C22:6 were higher in patients with carotid plaque. After data adjustments for age and LDL; energy, niacin, phosphorus and zinc remained significant. Conclusions We found nutritional differences between SLE patients with and without carotid atherosclerosis. The increased intake of certain fatty acids, and decreased intake of micronutrients including B-vitamins, may have etiological importance and will be investigated further. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1991