Risk of hospital admission for liver injury in users of NSAIDs and nonoverdose paracetamol: Preliminary results from the EPIHAM study

Sinem Ezgi Gulmez (1, 2) , Ulku Sur Unal (3) , Régis Lassalle (1, 2) , Anaïs Chartier (1, 2) , Adeline Grolleau (1, 2) , Nicholas Moore (1, 2)

1 CIC Bordeaux
2 Bordeaux PharmacoEpi, Inserm CIC1401, Université de Bordeaux
3 Tekirdağ Çerkezköy Tepe Emlak Family Medicine Centre

Purpose: The SALT study found similar per-user risks of acute liver failure (ALF) leading to transplantation (ALFT) between NSAIDs and a three-fold higher risk in non-overdose paracetamol (NOP) users. The objective of EPIHAM was to identify the risks of hospital admission for acute liver injury (ALI) associated with NSAIDs and NOP. Methods: Case-population study included in the 1/97 sample of the French population claims database. ALI was identified from hospital discharge summaries, from 2009 to 2013. Exposure for cases was dispensation of NSAID or NOP resulting in exposure within 30 days before admission. Population exposure was number of patients using the drugs over the study timeframe and total number of DDD dispensed. Results: Of 63 cases of ALI, 13 had been exposed to NSAIDs and 24 to NOP. Events per million DDD [95%CI] ranged from 0.46 [0.09-1.34] (ketoprofen) to 1.43 [0.04-7.97] (diclofenac combinations), 0.43 [0.23-0.73] all NSAIDs combined, 0.58 [0.37-0.86] for NOP. There was no association with average duration of treatment. Per patient risk ranged from 19.5 [5.31-49.9] (ibuprofen) per million users to 37.2 [19.8-63.6] all NSAIDs combined, 58.0 [37.2-86.3] for NOP. There was a linear relationship between average treatment duration and per-user risk (R2=0.51, p<0.05 for NSAIDs, R2=0.97, p<0.01 for NOP). Conclusions: Risk of hospital admission for ALI with NSAIDs and NOP were similar and indicative of a dose and duration-related effect (pharmacological) effect. ALI rates were not predictive of ALFT risk.

Mots clés: pharmacoepidemiology; claims database; paracetamol (acetaminophen); non-steroidal anti-inflammatory drugs (NSAIDs); drug-exposed hepatotoxicity; acute liver injury; Case-population study

Mots clés: étude cas-population; anti-inflammatoires non stéroïdiens; paracétamol; étude sur base de données; pharmacoépidémiologie; exposition médicamenteuse; hépatite aiguë

Domaines: Sciences pharmaceutiques; Hépatologie et Gastroentérologie; Santé publique et épidémiologie

Sinem Ezgi Gulmez, Ulku Sur Unal, Régis Lassalle, Anaïs Chartier, Adeline Grolleau, et al.. Risk of hospital admission for liver injury in users of NSAIDs and nonoverdose paracetamol: Preliminary results from the EPIHAM study. Pharmacoepidemiology and Drug Safety, 2018, 27 (11), pp.1174 - 1181. ⟨10.1002/pds.4640⟩. ⟨hal-01938473⟩