Detection of hypophosphatasia in hospitalised adults in rheumatology and internal medicine departments: a multicentre study over 10 years.

INTRODUCTION: Hypophosphatasia (HPP) is a rare genetic disease caused by loss-of-function mutations in the ALPL gene encoding the tissue non-specific alkaline phosphatase (ALP). Mild HPP is usually misdiagnosed in adult age. While an elevated serum ALP value draws more attention than a low value, low serum ALP should be better recognised and may lead to HPP detection. METHODS: Patients were selected from the records of the biochemistry department of six University Hospitals in France. Patients were hospitalised in the departments of rheumatology and internal medicine between 2007 and 2017. RESULTS: 56 321 hospitalised patients had at least 2 serum ALP dosages and 664 of these patients had at least 2 low serum ALP≤35 UI/L. Among these 664 patients, 482 (72.6%) had fluctuating low values (mean age 62.9 years; 60% of women) and 182 patients (27.4%) had persistent low values below 35 IU/L (mean age 53.4 years; 67% of women). Among patients with persistent hypophosphatasaemia treated with bisphosphonates, 70.8% never had ALP measurement before treatment and 20.8% were treated despite an abnormal decrease of ALP. Genetic testing was performed in 18 patients and was positive in 11. Genetic diagnosis of HPP was at least 6.0% in persistent hypophosphatasaemia and at least 15.9% in patients with at least three symptoms suggestive of HPP. CONCLUSION: In this 10-year retrospective study, 0.32% of adult patients hospitalised in the rheumatology and internal medicine departments had persistently low serum ALP, and among them, 6% had genetically proven HPP. Reported hypophosphatasaemia represented only 3.6% of hospitalised patients.

Trough infliximab concentrations predict efficacy and sustained control of disease activity in rheumatoid arthritis.

Infliximab is a chimeric monoclonal antibody that binds to human tumor necrosis factor alpha and is approved for refractory rheumatoid arthritis. We studied the association between infliximab concentration and long-term control of disease activity in patients with rheumatoid arthritis treated on a routine basis both in cross-sectional analysis and over the long term. Trough serum infliximab concentrations were measured in patients with rheumatoid arthritis receiving infliximab infusions during the period August to October 2006. Disease activity was assessed by the Disease Activity Score for 28 Joints (DAS28) and usual biologic markers. During a 42-week follow-up period, patients were classified into two groups: those continuing with the same or lower doses of infliximab (Group A = treatment success) and those who switched to another biopharmaceutical or required an increase in infliximab dose (Group B = treatment failure). Treatment maintenance for Group A was analyzed by categories of infliximab concentration at baseline and compared by the log rank test. In 28 patients, C-reactive protein and infliximab concentrations were inversely related. Infliximab concentration in patients with low disease activity (DAS28 3.2 or less) was higher than in those with persistent active disease (DAS28 greater than 3.2); median values were 3.26 and 0.16 mg/L, respectively (P < 0.01). Analysis after 42 weeks showed that patients in Group A had higher infliximab concentrations at baseline than those with treatment failure (P < 0.01). In rheumatoid arthritis, infliximab concentration is predictive of sustained efficacy with the same infliximab regimen and should be considered on a routine basis.

Management of osteoporosis in women after forearm fracture: data from a French health insurance database.

INTRODUCTION: Despite reliable diagnostic methods and effective drugs, the prevention and management of osteoporosis seems insufficient in France. We evaluated bone mineral density (BMD) assessment and prescription of anti-osteoporotic drugs after forearm fracture in women. METHODS: We used a health insurance database for outpatients from private clinics in a French population of more than 500,000 inhabitants. Medical expenses were analyzed for women 50 years of age or older who had a forearm fracture between August 1, 2010 and June 30, 2012. RESULTS: We identified 250 forearm fractures in women during the study period. In total, 12 women (4.8%) underwent BMD assessment before the fracture and were not taken into account in the analysis. For the 238 others, 24 (10.1%) had undergone BMD assessment at a median of 4 months after the fracture. A total of 32 women (13.4%) received an anti-osteoporotic drug at the time of the fracture and 14 of 206 untreated women (6.8%) received an anti-osteoporotic drug at a median of 3.8 months after the fracture. Receipt of an anti-osteoporotic drug was more frequent for women with than without BMD assessment after the fracture (8/19 [40.1%] versus 6/187 [3.2%]; P<0.005). CONCLUSION: This work, performed in a large sample, suggests that only 10% of women 50 years of age or older in France undergo BMD assessment after a forearm fracture and that BMD assessment is associated with anti-osteoporotic drug prescription.