M. Belhassen

What are the therapeutic alternatives to dextropropoxyphene in France? A prescribers' survey.

About a year after dextropropoxyphene (DXP) withdrawal from the French market, we conducted a survey among members of the French Society of Anesthesia & Intensive Care Medicine (Sfar) and of the French Society of the Study and Treatment of Pain (SFETD) to identify the indications for which this WHO level II analgesic had been prescribed, the prescribers feedback following withdrawal, and the substitutive analgesics prescribed. DXP had been prescribed by more than 75% of the 430 anaesthesiologists and 230 pain specialists interviewed, mainly for acute and chronic non-cancer pain of moderate intensity. While two thirds of pain specialists were not satisfied with DXP withdrawal, this decision did not affect the majority of anaesthesiologists. In both groups, the main substitutive analgesic was tramadol combined with acetaminophen, while only 24% of prescribers considered acetaminophen alone as a substitute.

Use of analgesics in France, following dextropropoxyphene withdrawal

BackgroundIn 2009, the European Medicines Agency recommended withdrawal of dextropropoxyphene (DXP); in March 2011 it was withdrawn from the market in France. Up until that time the combination dextropropoxyphene-paracetamol (DXP/PC) was widely used for analgesia. At withdrawal, French regulators recommended that DXP/PC be replaced by other step 2 analgesics, i.e. tramadol, codeine, or opium-containing drugs, or by PC for a weak level of pain. To investigate prescribing behaviours after DXP/PC withdrawal, dispensations of analgesics before and after withdrawal were analysed.MethodsAggregated dispensation data of analgesics prescribed between January 2009 and December 2012 in the Rhône-Alpes region were obtained from the general health insurance claims data; changes in analgesic dispensation over time were analysed with the ATC/DDD methodology. Pre (Jan-June 2009) and post-withdrawal (Jan-June 2012) changes of DDDs where computed for each analgesic step.ResultsThe dispensations of DXP/PC experienced a two-step decrease until 2011. Over the withdrawal period 2009-2012, there was a 14% decrease in the overall use of analgesic (from 109 to 94 DDDs), while the use of step 2 analgesics declined by 46% (− 22 DDDs, from 47 to 25 DDDs). This latter decline included a cessation of use of DXP/PC (29 DDDs in 2009) that were only in part (+ 7 DDDs, from 18 to 25 DDDs) compensated by increased use of codeine, tramadol and opium, in monotherapy or combined with PC. For step 1 analgesics, use increased with 9%, mostly PC (+ 8 DDDs, from 31 to 39 DDDs). Step 3 analgesics dispensations remained largely unchanged over this period (around 3 DDDs).ConclusionsIn the Rhône-Alpes region, DXP/PC withdrawal was accompanied in part by an increased use of same level analgesics, and in part by an increased use of PC in monotherapy. The extent of DXP/PC use before withdrawal, and the increased use of PC after DXP withdrawal, underline the complexity of pain management.

FRI0699 Determinants of 12-months persistence in ankylosing spondylitis patients initiating subcutaneous tnf-alpha inhibitors

Background Biotherapies such as subcutaneous tumour necrosis factor-alpha inhibitors (SC-TNFis) have transformed the management of inflammatory joint diseases such as ankylosing spondylitis (AS). The assessment of SC- TNFis persistence and its determinants is needed. Objectives The objective of this study was to describe treatment persistence in real-world settings, and identify the determinants of persistence among AS patients initiating treatment with an SC-TNFi. Methods The French national health insurance scheme database lists all outpatient and inpatient healthcare consumption for individuals covered by the general health insurance scheme. Using French claims data, AS was diagnosed using Long Term Disease status and hospital admission, based on ICD-10 codes. Patients were then identified through prescription filled for adalimumab (ADA), etanercept (ETA), certolizumab pegol (CZP) and golimumab (GLM) between 2012/07/01 and 2013/12/31. A patient was considered as non-persistent in the event of a prolonged interruption of the therapy lasting 91 days or more. Persistence was estimated with Kaplan Meier analysis. Determinants of persistence in the 12 months before initiation were identified using Cox models. Results A total of 9,098 patients with AS were identified. In the descriptive analyses of the 12 months persistence, differences were observed for AS patients, with raw/non-adjusted persistence rates of 33.2% for CZP, 49.3% for ETA, 52.4% for ADA and 54.5% for GLM. Results of the Cox model are presented, including hazard ratio for biotherapy, adjusted on sex, age, socio-economic status, and criteria on disease severity. The variables biotherapy, socio-economic status and hospital admission for IRMD did not meet the proportionality hypothesis of risks, and were corrected by the addition of a variable integrating the interaction with time.Table 1. Determinants of 12-month non-persistence (Cox model) Hazard Ratio IC 95% P-value SC-TNFis  GLM 1.000 – – –  CZP 2.707 2.139 3.426 <0.0001  ETA 1.915 1.665 2.203 <0.0001  ADA 1.418 1.286 1.565 <0.0001 Sex  Male 1.000 – – –  Female 1.377 1.300 1.458 <0.0001 Age 0.995 0.993 0.997 <0.0001 Deprived socio-economic status: Yes vs No 1.543 1.288 1.849 <0.0001 Number of comorbid conditions (per additional condition) 1.150 1.113 1.187 <0.0001 Biotherapy line (per additional line) 1.176 1.124 1.231 <0.0001 DMARD dispensation: Yes vs No 0.943 0.875 1.015 0.1182 Sulfasalazine dispensation: Yes vs No 0.996 0.915 1.084 0.9257 Long term oral steroids: Yes vs No 0.915 0.806 1.039 0.1719 Hospital admission for IRMD 0.883 0.792 0.984 0.0249 Visits to rheumatologist  0 1.000 – – –  1–4 0.925 0.800 1.070 0.2959  >4 0.958 0.829 1.108 0.5645 Interaction with time  Interaction biotherapy * time 1.001 1.001 1.001 <0.0001  Interaction socio-economic status * time 0.999 0.998 1.000 0.0132  Interaction hospital admission for IRMD * time 1.001 1.000 1.001 0.0335 Conclusions Non-persistent patients were more likely female, with deprived socio-economic status, multiple comorbid conditions, and multiple line of biotherapy. Age, hospital admission for IRMD and treatment with GLM (compared to CZP, ETA and ADA) decreased the risk of non-persistence. Further analyses are needed to assess the impact of non-persistence. Disclosure of Interest B. Fautrel Grant/research support from: AbbVie, MSD, Pfizer, Consultant for: AbbVie, Biogen, BMS, Celgène, Hospira, Janssen, Lilly, MSD, NORDIC Pharma, Pfizer, Roche, SOBI, UCB, M. Belhassen Employee of: PELyon, C. Hudry Consultant for: ABBVIE, MSD, BMS, PFIZER, ROCHE, CELGENE, NOVARTIS, BIOGEN, UCB, SANDOZ, AMGEN., Employee of: COCHIN Hospital, M.-C. Woronoff: None declared, N. Gouyette Employee of: MSD France, A. Clément Employee of: MSD France, E. Van Ganse Consultant for: PELyon; ALK ABELLO; AstraZeneca; Bayer; BMS; BIF; GSK; IMS; LASER; MSD, F. Tubach: None declared