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.

Drug maintenance of a second tumor necrosis factor alpha inhibitor in spondyloarthritis patients: A real-life multicenter study.

OBJECTIVES: Five TNF inhibitor (TNFi) agents are marketed for spondyloarthritis (SpA): 1 soluble receptor (SR) and 4 monoclonal antibodies (mAbs). From 15% to 30% of patients stop the first TNFi in the first 2 years, but we lack recommendations on the choice of the second TNFi. The aim here was to assess drug survival of a second TNFi in SpA and its determinants. METHODS: This was a multicenter observational study of SpA patients who started a first TNFi in 2013 and 2014 and were followed to 2018. For the first and second TNFi, we retrospectively collected data on initiation and discontinuation dates, type of TNFi, and reasons for withdrawal. Kaplan-Meier plots and log-rank tests were used to compare drug survival. Factors associated with drug survival of the second TNFi were analyzed by univariate Cox regression analyses. RESULTS: We included 244 patients. During a follow-up of 7,838 patient-months, 101 (41%) received 1 TNFi, and 143 (59%) switched to a second TNFi. Mean drug intake duration was significantly greater with the first than second TNFi: 21.7 (SD 19.6) and 15.4 (SD 13.6) months (P<0.001). When switching to another mAb or from an SR to an mAb (or the reverse), mean drug survival did not differ: 14.4 (SD 12.7) and 16 (SD 14.1) months (P=0.35). Factors associated with retaining the second TNFi were male sex (P=0.054) and age<41 years at SpA diagnosis (P=0.022). On multivariable analysis, only age<41 years at diagnosis remained independently associated with maintenance of the second TNFi. CONCLUSION: In SpA patients, drug survival is significantly longer with the first than second TNFi. Male sex and age<41 years at diagnosis were associated with retaining the second TNFi.