E.N. Van Roon

Efficacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol

Objectives: To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout, and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment. Methods: Prospective, multicentre, open-label, two-stage randomised controlled trial in gout patients with normal renal function. Enrolled patients were given 300 mg allopurinol for 2 months (stage 1). Those patients who could not tolerate allopurinol or who did not attain the target serum urate concentration (sUr) ⩽0.30 mmol/l (5.0 mg/dl), which was defined as successful, were randomised to benzbromarone 200 mg/day or probenecid 2 g/day for another 2 months (stage 2). Results: 96 patients were enrolled in stage 1. 82 patients (85%) were eligible for the analysis at the end of stage 1: there was a mean (SD) decrease in sUr concentration of 35 (11)% from baseline; 20 patients (24%) attained target sUr ⩽0.30 mmol/l; and 9 patients (11%) stopped allopurinol because of adverse drug reactions. 62 patients were enrolled in stage 2. 27 patients received benzbromarone (3 patients not eligible for analysis) and 35 received probenecid (4 patients not eligible for analysis). Treatment with benzbromarone was successful in 22/24 patients (92%) and with probenecid in 20/31 patients (65%) (pu200a=u200a0.03 compared with benzbromarone). Compared with baseline values, there was a mean (SD) decrease of sUr concentration of 64 (9)% with benzbromarone and 50 (7)% with probenecid (p<0.001). Conclusion: This study showed that allopurinol 300 mg/day has a poor efficacy and tolerability profile when used to attain a biochemical predefined target level of sUr ⩽0.30 mmol/l, following 2 months of treatment. In stage 2, benzbromarone 200 mg/day was more effective and better tolerated than probenecid 2 g/day. Trial registration number: ISRCTN21473387.

Safety and efficacy of leflunomide in primary Sjögren’s syndrome: a phase II pilot study

Background: For invalidating symptoms in primary Sjögren’s syndrome (pSS), there is still a need for easy-to-administer, cost-effective and well-tolerated systemic treatment. Leflunomide (LEF) is structurally unrelated to other immunomodulatory drugs and might be efficacious in pSS, given its characteristic immunoregulatory modes of action. Objective: To investigate the safety and efficacy of LEF in pSS in a phase II open-label pilot study. Methods: 15 patients with pSS with early and active disease received LEF 20 mg once daily for 24 weeks. Tolerability, safety and efficacy of LEF were evaluated every 8 weeks. Additional safety visits were performed every fortnight. Results: Mild gastrointestinal discomfort (including diarrhoea) and hair loss were mainly reported. Five patients developed lupus-like skin lesions on the face, arms or trunk, responding well to topical corticosteroids, nevertheless causing the withdrawal of one patient. Two patients with pre-existing hypertension had to increase dosages of anti-hypertensive drugs. Increased levels of alanine aminotransferase normalised after dose reduction in two patients. A decrease in general fatigue and an increase in physical functioning were observed after 24 weeks. Serum IgG levels decreased from 8 weeks onwards. Schirmer test values increased, not reaching statistical significance, whereas sialometry values did not change. In four of five repeated biopsies, the lymphocytic focus score decreased at the rate of 1 focus/4 mm2. A remarkable amelioration of leucocytoclastic vasculitis was observed in three patients. Conclusions: Although the safety profile seems fairly acceptable, the observed indications for efficacy were modest and may be doubtful in justifying a randomised controlled trial of LEF in pSS.

Doctors’ beliefs and knowledge on corticosteroid‐induced osteoporosis: identifying barriers to improve prevention

What is known and Objective:u2002 Despite the availability of effective treatments for the management of corticosteroid‐induced osteoporosis (CIOP), the condition is undertreated. Our objective was to assess prescribers’ knowledge and likely prescribing patterns concerning the diagnosis and treatment of CIOP. Another goal was to identify key barriers to the use of preventive therapy in patients using long‐term corticosteroids.

Initiation of oral anticoagulant therapy in orthopedic and surgical patients : an algorithm compared with routine dosing

Abstract. Oral anticoagulant therapy is initiated in most hospitals in The Netherlands by clinicians who routinely dose oral anticoagulants (without using an algorithm). This may explain the low proportion of patients leaving the hospital stabilized. To test this hypothesis this study compared the dosing of acenocoumarol in orthopedic and surgical patients using an algorithm with routine dosing. Because of the routine administration of low molecular weight heparin for at least the first 5xa0days of acenocoumarol therapy, the study focused on supratherapeutic INR-values during this period. The study included 103 patients and was performed on orthopedic surgery and general surgery wards of a Dutch hospital over 5xa0months. The patients received acenocoumarol as an oral anticoagulant to prevent venous thromboembolism after general of orthopedic surgery. Patients were randomized into a group routinely dosed by physicians (n=54) and a group dosed using a dosing algorithm (n=49). A patient was defined as stable if he had two consecutive INR values within the range of 2–3 during hospitalization with the first (of the two consecutive INR values within range) having been measured on day 5 or later. The groups did not differ significantly in proportion of patients stabilized, time to stabilization, or length of hospitalization. In the first period (days 1–5) the routine dosing group had significantly more INR values above therapeutic range than the algorithm group, while the algorithm group had more INR values below the therapeutic range. There were two bleeding episodes in the routine dosing group and none in the algorithm group. Despite the lack of differences in stabilization between the two groups, this study suggests an advantage of dosing acenocoumarol using an algorithm in a study population consisting of prophylactically treated, mostly elderly orthopedic patients. The algorithm provides a safe dosing schedule for elderly postoperative patients who use low molecular weight heparin and NSAIDs concomitantly and are thus at high risk for bleeding complications.

Bridging the gap between the randomised clinical trial world and the real world by combination of population-based registry and electronic health record data: A case study in haemato-oncology

Randomised clinical trials (RCTs) are considered the basis of evidence-based medicine. It is recognised more and more that application of RCT results in daily practice of clinical decision-making is limited because the RCT world does not correspond with the clinical real world. Recent strategies aiming at substitution of RCT databases by improved population-based registries (PBRs) or by improved electronic health record (EHR) systems to provide significant data for clinical science are discussed. A novel approach exemplified by the HemoBase haemato-oncology project is presented. In this approach, a PBR is combined with an advanced EHR, providing high-quality data for observational studies and support of best practice development. This PBRxa0+xa0EHR approach opens a perspective on randomised registry trials.

Treatment of pregnant and non-pregnant rheumatic patients: a survey among Dutch rheumatologists

Background:u2002 The aim of this study was to explore, among Dutch rheumatologists, aspects such as attitude towards guidelines, pharmacotherapy and information needs in the treatment of pregnant as well as non‐pregnant rheumatoid arthritis (RA) patients.

The effect of bisphosphonates on bone mineral density in patients with ankylosing spondylitis in daily clinical practice

Background Ankylosing spondylitis (AS) is not only characterized by excessive bone formation, but also by excessive bone loss which may lead to low bone mineral density (BMD). So far, little is known about the effect of treatment with bisphosphonates on BMD in patients with AS. Objectives To evaluate the effect of bisphosphonates in combination with calcium/vitamin D supplements on BMD over 2 years in patients with AS stratified for the use of TNF-α inhibitors. Methods Patients from the Groningen Leeuwarden AS (GLAS) cohort, fulfilling the modified New York criteria for AS, who were treated with bisphosphonates and had 2-year follow-up BMD measurements available were included. All patients were treated with bisphosphonates in combination with calcium and/or vitamin D supplements. Alendronate (70 mg/week) and risedronate (35 mg/week) were used most frequently. BMD of the lumbar spine (anterior-posterior projection at L1-L4) and hip (total proximal femur) were measured using DXA. Wilcoxon-signed rank test was used to compare BMD scores at first visit and after 2 years. Analyses were stratified for the use of TNF-α inhibitors. Results In total, 28 patients were included; 68% were male, 82% HLA-B27+, mean age was 53 ± 14 years, median symptom duration 20 years (range 1–60), and mean BASDAI 5.1±2.5. Fifteen patients (54%) started treatment with bisphosphonates before inclusion in the GLAS cohort (median 3.1 years). Most patients (86%) used bisphosphonates during the entire 2-year follow-up within GLAS. Overall, lumbar spine BMD increased significantly from median Z-score of -0.8 at first visit to -0.3 after 2 years of treatment with bisphosphonates within the GLAS cohort. Hip BMD increased significantly from -1.1 at first visit to -0.9 after 2 years. In the 10 patients not using TNF-α inhibitors, only lumbar spine BMD increased significantly after 2 years of treatment. In the 14 patients starting TNF-α inhibitors, lumbar spine and hip BMD increased significantly after 2 years. The remaining 4 patients already used TNF-α inhibitors (Table 1). Comparable results were found for BMD T-scores. Conclusions In our observational cohort study, lumbar spine BMD improved significantly after 2 years of follow-up in all AS patients treated with bisphosphonates. This improvement was most pronounced in patients starting TNF-α inhibitors. Hip BMD only improved significantly in patients also starting TNF-α inhibitors. Acknowledgement The GLAS cohort was supported by an unrestricted grant from Pfizer. Pfizer had no role in the design, conduct, interpretation, or publication of this study. Disclosure of Interest S. Arends Grant/research support from: Pfizer, J. Veneberg: None declared, F. Wink Consultant for: Abbvie, R. Bos Grant/research support from: Pfizer, E. Brouwer Grant/research support from: Pfizer, E. van der Veer: None declared, H. Bootsma: None declared, E. van Roon: None declared, F. Maas: None declared, A. Spoorenberg Grant/research support from: Abbvie, Pfizer, UCB, Consultant for: Abbvie, Pfizer, MSD, UCB, Novartis

Doctors’ beliefs and knowledge on corticosteroid-induced osteoporosis: identifying barriers to improve prevention: Doctors’ knowledge on CIOP prevention

What is known and Objective:u2002 Despite the availability of effective treatments for the management of corticosteroid‐induced osteoporosis (CIOP), the condition is undertreated. Our objective was to assess prescribers’ knowledge and likely prescribing patterns concerning the diagnosis and treatment of CIOP. Another goal was to identify key barriers to the use of preventive therapy in patients using long‐term corticosteroids.

Treatment of pregnant and non-pregnant rheumatic patients: a survey among Dutch rheumatologists: Treatment of patients with a rheumatic disease

Background:u2002 The aim of this study was to explore, among Dutch rheumatologists, aspects such as attitude towards guidelines, pharmacotherapy and information needs in the treatment of pregnant as well as non‐pregnant rheumatoid arthritis (RA) patients.

Is toediening van allopurinol bij jicht ten gevolge van diuretica bij hartfalen zinvol

Het korte antwoord op deze vraag luidt: ‘ja, want iedere verlaging van serumuraatconcentratie geeft een verlaging van risico op jichtaanvallen’. Uiteraard verdient deze korte beantwoording nog wel wat bespiegeling. Bij diureticagebruikers dringen de volgende vragen zich op: Kan het staken van een urinezuurverhogend diureticum alleen al een afdoende zinnige actie zijn? Of dient urinezuurverlaging perse door middel van een xanthine-oxidaseremmer (XOR) en/of uricosuricum te worden bereikt? Welk lijden volgt er eigenlijk uit door-diuretica-verhoogde urinezuurconcentraties? En, is er bewijs voor de werking van XOR bij jicht secundair aan urinezuurspiegelverhogende diuretica? In het onderstaande willen we de “evidences” belichten.