title: French Nationwide Cohort Temporary Utilization Authorization Survey of GranuPAS(®) in MDR-TB patients.
abstract: BACKGROUND
  Para-aminosalicylic acid (PAS) is again needed for the treatment of multidrug and extensively drug-resistant tuberculosis (M/XDR-TB). The study of a new granulated formulation (PAS-GR, 'GranuPAS(®)'), which might have fewer adverse events, was made possible by the statutory requirement that data be collected regarding its use in France in multidrug-resistant TB (MDR-TB) patients under a 'therapeutic utilization' follow-up for safety and efficacy system called 'Autorisation Temporaire d'Utilisation' (ATU).
  
  
  METHODS
  In May 2011 an ATU cohort was established to monitor the named patient use of PAS-GR. All patients were included in a follow-up protocol developed by Lucane Pharma and the French Medicines Agency (ANSM) which recorded demographics, dosing characteristics, concomitant medications, adverse events, and outcome. Following EU marketing authorization, the ATU terminated about 3 years after initiation.
  
  
  RESULTS
  PAS-GR was used for the treatment of 231 MDR-TB patients. PAS-GR was used at 12 g/day in 114 cases and 8 g/day in 80 cases. PAS-GR-containing combinations resulted in sputum conversion in a median of 94 days (IQR 48-143) in the 55 patients with information after treatment initiation. Adverse effects of PAS-GR-containing combinations were mostly gastrointestinal (GI; 9% of patients experiencing a GI event at any time) and led to interrupt PAS-GR in 6% of cases (2.1% GI).
  
  
  CONCLUSIONS
  The efficacy of PAS-GR appears equivalent to that of PAS, and its tolerance improved over earlier PAS formulations, thus supporting the use of PAS-GR as part of drug combinations for the treatment of MDR and XDR-TB.
authors.affiliation: Lucane Pharma, UPMC University of Paris, Sorbonne Universités, Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Kibleur
authors.forename: Nicolas
authors.initials: N
authors.lastname: Veziris
mesh_terms: D000328:Adult; D010131:Aminosalicylic Acid / Q000009:adverse effects* / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy*; D005260:Female; D005602:France; D006801:Humans; D008297:Male
chemical_list: D000995:Antitubercular Agents; D010131:Aminosalicylic Acid