L.A. Rasch

Glucocorticoid safety for treating rheumatoid arthritis

Introduction: Glucocorticoids (GCs) are often used in the treatment of rheumatoid arthritis and many other inflammatory diseases. Besides strong favorable effects on disease activity, GCs can cause (serious) side effects as well. Areas covered: Side effects of GCs that are ranked as most important by rheumatologists as well as by patients are bone loss and fractures, cardiovascular events, hypertension, and diabetes mellitus. In evaluating these side effects, confounding by indication is a disturbing factor: not only the use of GCs can increase the risk of several side effects, but so can the activity of the underlying disease, which in turn is related to the amount of GCs that is prescribed to the patient. Expert opinion: Generally, side effects predominantly occur in patients with a high disease activity and when used in high doses and for a long period of time. For these patients, caution and monitoring are most warranted. However, monitoring is not only recommended in patients with a high disease activity, and high-dose or long-term use of GCs, but in all GC users, since side effects may also occur in patients treated with low-dose GCs. When detecting possible negative effects in time, they might be managed and serious damage due to side effects might hopefully be prevented.

Validating Rheumatoid Arthritis Remission Using the Patients’ Perspective: Results from a Special Interest Group at OMERACT 2016

Objective. The Outcome Measures in Rheumatology (OMERACT) working group on the patients’ perspective on remission in rheumatoid arthritis (RA) has been working on this topic since 2010. At OMERACT 2016, progress and preliminary data on validity of measurement instruments for pain, fatigue, and independence in remission in RA were presented, and future directions were explored. Methods. A special interest group was organized, in which the current data on the patients’ perspective on remission were presented. The ongoing study that aimed to validate measurement instruments for pain, fatigue, and independence in a state of low disease activity or remission was presented, and preliminary data on construct validity and discriminative capacity were evaluated cross-sectionally. Results. At OMERACT 2016, the progress of the working group and preliminary data from 142 of the anticipated 300 patients were presented. Selected instruments significantly correlated with the Disease Activity Score in 28 joints (construct validity) and all instruments except 1 discriminated between patients in and patients not in remission. The subsequent discussion mainly focused around 3 points: (1) the formulation of patient perceived remission, (2) the duration of remission, and (3) the measurement of the domain independence. An informal vote indicated a slight preference for working toward modifying the current remission criteria by adding patient-reported outcomes (PRO), or by substituting the patient’s global assessment with 1 or more PRO. Conclusion. More evidence on measuring patients’ perspective on remission in RA is needed before an informed decision can be made regarding development or modification of remission definitions.

OP0106 Change in Bone Mineral Density with High-Dose Prednisone in Patients with Rheumatoid Arthritis

Background Recently, we showed that treatment with COBRA-light therapy including prednisone with initially 30 mg/day, was as effective as the original COBRA scheme, with initially 60 mg/day [1,2], in the treatment of rheumatoid arthritis (RA). Since high-dose glucocorticoids are associated with bone loss and vertebral and nonvertebral fractures, we investigated the differences in bone mineral density (BMD) after one year of treatment in both arms. Objectives To compare 1-year changes in BMD (lumbar spine [L1-L4], total hip, and femoral neck) between the treatment groups. Methods An open-label, randomised controlled, non-inferiority trial of patients with active, newly diagnosed RA following a treat-to-target protocol. Results BMD data were determined in 144 out of 164 included RA patients, all randomized to either COBRA (n=71) or COBRA-light (n=73) therapy. Overall bone loss was very limited, and no significant difference in change in BMD between COBRA and COBRA-light was found at any site (Table 1). However, in secondary analyses, COBRA-light showed a significant decrease in BMD in the lumbar spine and total hip after 52 weeks, whereas the femoral neck and the COBRA group did not.Table 1. Changes in bone mineral density between baseline and week 52 during COBRA and COBRA-light therapy COBRA (n=71) COBRA-light (n=73) baseline week 52 change baseline week 52 change Lumbar spine 1.12 (0.17) 1.12 (0.17) 0.01% 1.10 (0.15) 1.09 (0.15) −1.02%* Total hip 0.95 (0.14) 0.95 (0.14) 0.05% 0.95 (0.12) 0.94 (0.13) −1.16%* Femoral neck 0.90 (0.16) 0.89 (0.17) −0.59% 0.88 (0.12) 0.87 (0.11) −0.98%* *Significant change between baseline and week 52 (p<0.05). Values are reported as mean (SD), unless otherwise specified. Conclusions During the trial, overall bone loss was very limited and not significantly different between the treatments. These findings strengthen the hypothesis that positive effects associated with the large reduction in disease activity as a result of combination therapy and tight control treatment counteract the negative effects of (high-dose) prednisone on bone. References Den Uyl D, et al. Ann Rheum Dis 2014; Ter Wee MM, et al. Ann Rheum Dis 2015 Disclosure of Interest L. Rasch: None declared, L. van Tuyl: None declared, M. Kremer: None declared, I. Bultink: None declared, M. Boers: None declared, W. Lems Grant/research support from: This research was performed within the framework of project T1–106 of the Dutch Top Institute Pharma, and was additionally funded by an unrestricted grant from Pfizer.

Estimation of dietary calcium intake

Dear Editor,With great pleasure we read the article by Macdonaldet al., describing the validation of a 23-item question-naire for estimating dietary calcium intake, the CaQ [1].We encourage this initiative as we are in search of aneasy, accurate, and feasible way to estimate the calciumintake of our patients as well.Recently, there has been a lot of attention for thepossible elevated cardiovascular risks of surplus calciumsupplementation on the one hand and calcium deficien-cy on the other hand in patients with osteoporosis. Tobe able to prescribe the adequate amount of calciumsupplementation, a practical tool to validly estimate thedietary intake of calcium is not available to clinicians.Most dietary assessment methods are too time-consuming for clinical practice. The gold standard ofassessing dietary calcium intake is a 7-day food diarywith weighed portion sizes, which is laborious for cli-nicians as well as for patients, and therefore not feasiblein clinical practice. Food frequency questionnaires(FFQ) are far more practical; however, they still consistof many questions and thus are not feasible in clinicalpractice either.Macdonald et al. validated their 23-item CaQ againsttwo “gold standards”: a 7-day food diary (n=33), whichis close to a real gold standard, although portion sizeswere estimated rather than weighed, and a FFQ (n=72),which is similar to the CaQ except for being moreelaborate. The authors conclude that their CaQ is anadequate tool to assess daily calcium intake when scor-ing between 700 and 1,200 mg.Although we were excited to see the work ofMacdonald et al., we missed a detailed report on thenumber of patients that has an estimated calcium intakeoutside a predefined clinically relevant area. Forexample, if an intake of 1,000 mg would be considerednormal, a difference of 250 mg between the goldstandard and the questionnaire would be clinicallyrelevant, as patients below 750 mg would benefit fromsupplementation. From a clinician’s perspective, it isimportant to know how many patients fall within theclinically relevant area, in order to judge the applicabilityof the CaQ for prescription of calcium supplements topatients.We recently validated a calcium intake list with only threeitems, which underestimated calcium intake compared toa dietary history with a clinically relevant difference ofmore than 250 mg in 56 % of patients [2]. Using ourlist to prescribe calcium supplements would mean thattoo many patients would be given too much calcium,possibly resulting in elevated cardiovascular risks.Currently, we are in the process of refining the list inorder to improve sensitivity and specificity for use inclinical practice.We look forward to validation studies of calciumintake lists in other cohorts of osteoporosis patients tosee if these lists are valid across cultures and diets andto decide on clinically relevant cutoff points for theprescription of calcium medication.

AB0287 High Levels of 25(OH)D Are Associated with Lower Disease Activity in Patients with Newly Diagnosed Rheumatoid Arthritis: Table 1.

Background Vitamin D deficiency is highly common in patients with rheumatoid arthritis (RA) (1). In vitro, vitamin D has anti-inflammatory effects and vitamin D has been linked to disease activity in RA due to its immuno-modulatory properties (1,2). Objectives To investigate the association between vitamin D status and disease activity in newly diagnosed RA patients before start of therapy. Methods Consecutive patients with active, newly diagnosed RA (symptom duration <2 years), were randomized for treatment with COBRA or COBRA-light therapy (3). Before start of therapy, baseline values were determined, including Disease Activity Score (44 joint; DAS) and serum 25-hydroxy vitamin D (25(OH)D) levels. Based on the widely used cut-off values, patients were stratified into three groups based on baseline serum 25(OH)D levels: <50 nmol/l, 50-74 nmol/l, and ≥75 nmol/l. Results Baseline serum 25(OH)D levels were determined in 147 of 164 included RA patients in the COBRA-light trial (90% of trial population). Serum 25(OH)D levels of the different groups are presented in Table 1. Patients with a baseline serum 25(OH)D level ≥75 nmol/l had a significant lower mean DAS compared to patients with a baseline serum 25(OH)D <75 nmol/l (p=0.001). Vitamin D deficient patients (<50 nmol/l) had a significant shorter symptom duration (p=0.003), and were more often rheumatoid factor positive (p=0.015) compared to patients with sufficient serum 25(OH)D levels.Table 1. Vitamin D status and disease related factors of patients with newly diagnosed rheumatoid arthritis before start of therapy Serum 25(OH)D Serum 25(OH)D Serum 25(OH)D <50 nmol/l 50–74 nmol/l ≥75 nmol/l (n=62; 42%) (n=50; 34%) (n=35; 24%) Disease Activity Score (DAS, 44 joints) 4.2 (0.7) 4.0 (0.9) 3.6 (0.7)* Symptom duration (weeks) 12 [8,21]* 18 [8,49] 25 [13,36] Health Assessment Questionnaire score (HAQ, 0 to 3) 1.5 (0.8) 1.3 (0.6) 1.2 (0.6) Serum 25(OH)D (nmol/l) 36 [25,46] 61 [54,67] 87 [81,100] Rheumatoid factor positive (n (%)) 44 (72)† 22 (45) 20 (57) aCCP positive (n (%)) 44 (71) 26 (53) 25 (71) Values are reported as mean (SD) or median [IQR], unless otherwise specified. *Differs significantly from both other groups (p-value<0.05); †Differs significantly from serum 50-74 nmol/l (p-value<0.05). 25(OH)D: 25-hydroxy vitamin D; aCCP: antibodies against cyclic citrullinated peptides. Conclusions Newly diagnosed RA patients with serum 25(OH)D levels ≥75 nmol/l demonstrate a significant lower disease activity than patients with a serum 25(OH)D level <75 nmol/l before start of therapy. This study cannot distinguish whether a lower DAS at baseline is caused by immuno-modulatory properties due to higher serum 25(OH)D levels, or that higher serum 25(OH)D levels are caused by more frequent outdoor activities related to a lower DAS. Since 75% of the newly diagnosed RA patients have insufficient serum 25(OH)D levels (<75 nmol/l), vitamin D supplementation should be considered in every newly diagnosed RA patient. References Grazio S, et al. Am J Med Sci 2014. Baker JF, et al. Clin Exp Rheumatol 2012. Den Uyl D, et al. Ann Rheum Dis 2013. Disclosure of Interest L. Rasch: None declared, N. Konijn: None declared, Y. Krul-Poel: None declared, L. van Tuyl: None declared, H. Raterman: None declared, M. ter Wee: None declared, D. den Uyl: None declared, S. Simsek: None declared, M. Nurmohamed: None declared, W. Lems Grant/research support from: This research was performed within the framework of project T1-106 of the Dutch Top Institute Pharma, and was additionally funded by an unrestricted grant from Pfizer.

AB0900 A Short, Quick, and Easy Questionnaire to Estimate Daily Dietary Calcium Intake of Osteoporosis Patients

Background Calcium supplements are widely used for the prevention and treatment of osteoporosis. However, recent literature suggests that too much calcium supplementation may be associated with cardiovascular events (1). For this reason, calcium supplementation should be based on actual and adequate dietary calcium intake. A previously designed calcium intake list appeared to be invalid (2) and other alternatives are too time consuming for clinical practice. Therefore, we developed a new calcium intake list, to accurately estimate dietary calcium intake, which was validated in this study. Objectives The aim of this study is to validate a short, quick, and easy calcium intake list, to be able to estimate dietary calcium intake, with an extensive dietary history (DH) as a reference method. Methods This cross-sectional study included consecutive patients attending the outpatient rheumatology department at the VUmc in Amsterdam, the Netherlands, for the treatment of primary or secondary osteoporosis. Based on the food groups which contribute most to daily dietary calcium intake and portion sizes determined from our earlier validation study (2), a short three-item calcium intake list was designed. As a reference method, an extensive DH with specific focus on calcium products and extra attention for portion sizes was performed. Before starting the study, a difference of 250 mg calcium or more between both methods was determined as clinically relevant. Performing the short calcium intake list took about 3 minutes, performing the DH took 60 minutes. Results In this study, 66 patients with primary (n=40) and secondary (n=26) osteoporosis were included. The three-item calcium intake list showed a small, clinically non-relevant, difference with the DH of 25±350 mg calcium per day (p=0.568), see table 1. Sensitivity and specificity of the short calcium intake list, compared to the DH, were respectively 73% and 80%. In 50% of the individuals, a clinically relevant difference of 250 mg calcium or more was observed between the calcium intake list and the DH, while in 17% a difference of 500 mg or more was observed.Table 1. Mean ± SD daily calcium intake of patients with osteoporosis estimated by the calcium intake list versus dietary history Calcium intake (mg/day) Difference (mg) P-value Short calcium intake list Dietary History 1146±440 1170±485 25±350 0.568 *Significant difference between the calcium intake list and dietary history. Conclusions The short calcium intake list is a three-item, quick and easy questionnaire to accurately estimate dietary calcium intake of osteoporosis patients at a group level, and thus very helpful for clinical studies. However, in individual patients, clinicians should be aware of not identifying a deficient calcium intake in approximately 20% of the patients, and of prescribing supplements to patients with a sufficient intake in approximately 30% of patients. Remarkably, mean calcium intake is around the current Dutch recommendation of 1000-1200 mg calcium per day. This indicates that a large proportion of the osteoporosis patients might not even need calcium supplementation. References Bolland MJ, et al. BMJ 2010. (2) Rasch LA, et al. Austin J Nutri Food Sci 2014. Disclosure of Interest None declared

SAT0359 Rheumatologists underestimate daily calcium intake in patients with osteoporosis

Background Calcium supplements are widely used for the prevention and treatment of osteoporosis. However, in recent literature there is a controversy whether or not excessive calcium supplementation may be associated with increased risk of cardiovascular events (1-2). In daily practice, rheumatologists at the VUmc use a short calcium list to estimate the dietary intake of calcium, which is the basis for the prescribed amount of calcium supplementation. An accurate estimation is important to be able to prescribe the adequate amount of calcium supplementation to reach the recommended levels of 1000-1200 mg of calcium per day, without a possible increase of the risk of cardiovascular events. Objectives Validation of a short calcium intake list used by rheumatologists with a detailed dietary history (DH), assessed by a dietician, as the reference method. Methods This cross-sectional study included patients attending the outpatient department of rheumatology at the VUmc for the treatment of primary or secondary osteoporosis. For participating in this study, subjects had to be diagnosed with and treated for osteoporosis, based on a low T-score in hip and/or lumbar spine, with or without a vertebral fracture. In addition, subjects in the group of secondary osteoporosis had to be diagnosed with a rheumatic disorder. The short calcium list calculated calcium intake by asking for the amount of portions of milk, yoghurt (multiplied by 180 mg of calcium per portion), and cheese (multiplied by 155 mg of calcium per portion). In addition, 250 mg of calcium from other products was added. This short list was compared with a DH with specific focus on calcium products and extra attention for portion sizes of dairy products and cheese. On forehand, a difference of at least 250 mg of calcium between both methods was formulated as clinically relevant. Results Sixty-six subjects (31 with primary osteoporosis and 35 with secondary osteoporosis) were included. The mean nutritional calcium intake measured via the short calcium list (825±259 mg) was lower than via the DH (1113±424 mg) (p<0.001). Furthermore, the mean difference between both methods was 289±346 mg of calcium: in 37 of the 66 patients (56.1%) the short calcium list scored more than 250 mg lower than the DH, and in only 4 of the 66 patients (6.1%) the short calcium list scored more than 250 mg higher than the DH. In total, 55 patients (83.3%) reached an overall intake higher than the upper limit of the recommendation of 1200 mg of calcium per day. Conclusions The short calcium list gives a substantial and clinically relevant underestimation of dietary calcium intake in more than 55% of the patients. Therefore, the short calcium list is not a valid method to measure calcium intake of patients with osteoporosis. This is a clinically relevant finding because of the rumour around an increased risk of cardiovascular events associated with a too high overall calcium intake. References Bolland MJ, et al. BMJ 2008 Feb 2;336(7638):262-6. Lewis JR, et al. J Bone Miner Res 2011 Jan;26(1):35-41. Disclosure of Interest None Declared