Drug Saf. 2013 Feb;36(2):135-44. doi: 10.1007/s40264-012-0013-7.
Transplantation for acute liver failure in patients exposed to NSAIDs or paracetamol (acetaminophen): the multinational case-population SALT study.
Gulmez SE, Larrey D, Pageaux GP, Lignot S, Lassalle R, Jové J, Gatta A, McCormick PA, Metselaar HJ, Monteiro E, Thorburn D, Bernal W, Zouboulis-Vafiadis I, de Vries C, Perez-Gutthann S, Sturkenboom M, Bénichou J, Montastruc JL, Horsmans Y, Salvo F, Hamoud F, Micon S, Droz-Perroteau C, Blin P, Moore N.
INSERM CIC-P0005 Pharmaco-épidémiologie, INSERM U657, Service de Pharmacologie, Université Bordeaux Segalen, Bâtiment Le Tondu, Case 41, 146, Rue Léo Saignat, 33076 Bordeaux Cedex, France. sinemezgi.gulmez@u-bordeaux2.fr
BACKGROUND:
Most NSAIDs are thought to be able to cause hepatic injury and acute liver failure (ALF), but the event rates of those leading to transplantation (ALFT) remain uncertain.
OBJECTIVES:
The aim of the study was to estimate population event rates for NSAID-associated ALFT METHODS: This was a case-population study of ALFT in 57 eligible liver transplant centres in seven countries (France, Greece, Ireland, Italy, The Netherlands, Portugal and the UK). Cases were all adults registered from 2005 to 2007 for a liver transplant following ALFT without identified clinical aetiology, exposed to an NSAID or paracetamol (acetaminophen) within 30 days before the onset of clinical symptoms. NSAID and paracetamol population exposures were assessed using national sales data from Intercontinental Marketing Services (IMS). Risk was estimated as the rate of ALFT per million treatment-years (MTY).
RESULTS:
In the 52 participating centres, 9479 patients were registered for transplantation, with 600 for ALFT, 301 of whom, without clinical aetiology, had been exposed to a drug within 30 days. Of these 301 patients, 40 had been exposed to an NSAID and 192 to paracetamol (81 of whom were without overdose). Event rates per MTY were 1.59 (95 % CI 1.1-2.2) for all NSAIDs pooled, 2.3 (95 % CI 1.2-3.9) for ibuprofen, 1.9 (95 % CI 0.8-3.7) for nimesulide, 1.6 (95 % CI 0.6-3.4) for diclofenac and 1.6 (95 % CI 0.3-4.5) for ketoprofen. For paracetamol, the event rate was 3.3 per MTY (95 % CI 2.6-4.1) without overdoses and 7.8 (95 % CI 6.8-9.0) including overdoses.
CONCLUSIONS:
ALF leading to registration for transplantation after exposure to an NSAID was rare, with no major difference between NSAID. Non-overdose paracetamol-exposed liver failure was twice more common than NSAID-exposed liver failure.
Curr Med Res Opin. 2012 Sep;28(9):1537-45. Epub 2012 Aug 16.
Efficacy and safety of celecoxib versus diclofenac and omeprazole in elderly arthritis patients: a subgroup analysis of the CONDOR trial.
Kellner HL, Li C, Essex MN.
Division of Rheumatology, Center for Inflammatory Joint Diseases, Munich, Germany. hk@prof-dr-kellner.de
OBJECTIVE:
To compare the safety and efficacy of celecoxib versus diclofenac slow release (SR) plus omeprazole in elderly arthritis patients.
RESEARCH DESIGN AND METHODS:
Patients aged=65 years, with osteoarthritis and/or rheumatoid arthritis, at high gastrointestinal (GI) risk who participated in the CONDOR trial (Celecoxib vs. Omeprazole and Diclofenac in Patients With Osteoarthritis and Rheumatoid Arthritis) were included in this subanalysis. CONDOR was a 6-month prospective, double-blind, randomized, parallel-group, multicenter, international study comparing treatment with celecoxib 200?mg twice daily (BID) versus diclofenac SR 75?mg BID plus omeprazole 20?mg daily.
MAIN OUTCOME MEASURES:
The primary end point was a composite of Clinically Significant Upper and Lower GI Events adjudicated by an independent blinded expert committee. Efficacy was determined by the Patient's Global Assessment of Arthritis.
RESULTS:
A total of 2446 patients aged=65 years were included in the intent-to-treat (ITT) population (n=1219 celecoxib; n=1227 diclofenac). Eight patients in the celecoxib group and 52 in the diclofenac group were adjudicated as having Clinically Significant Upper and Lower GI events (adjusted odds ratio: 6.27; p<0.0001). Clinically significant reductions in hemoglobin (=2?g/dL) and/or hematocrit (=10%) were observed in 23 patients in the celecoxib group and in 76 in the diclofenac group (relative risk: 3.22 [95% confidence interval: 2.04-5.07]; p<0.0001). Incidence of moderate-to-severe abdominal symptoms and discontinuation of treatment due to GI adverse events (AEs) were lower in the celecoxib group. The Patient's Global Assessment of Arthritis score least squares mean change from baseline to final visit and percentage of patients rating treatment efficacy as good/very good at baseline and final visit were similar in both groups.
LIMITATIONS:
The dose of celecoxib used is consistent with the European label for the management of osteoarthritis and may not reflect what is commonly prescribed in current clinical practice in the United States. The data were obtained in a clinical trial setting where patients were enrolled based on specific inclusion and exclusion criteria; as such, the patients may not be broadly representative of the patient population in a general practice setting.
CONCLUSIONS:
Efficacy was comparable in the two treatment groups. There were fewer endpoints as well as fewer GI AEs reported in patients treated with celecoxib compared with diclofenac. These data may help physicians in their treatment decisions for elderly patients with arthritis. |
