title: Nearly pain-free self-administration of subcutaneous methotrexate with an autoinjector: results of a phase 2 clinical trial in patients with rheumatoid arthritis who have functional limitations.
abstract: BACKGROUND
  A methotrexate autoinjector (MTXAI) was developed for self-administration of subcutaneous (SC) methotrexate by patients with rheumatoid arthritis (RA). The MTXAI circumvents the need for vials, needles, and syringes and may therefore improve dosing accuracy, handling risks, and patient adherence.
  
  
  OBJECTIVE
  The objective of this study was to evaluate actual human use of the MTXAI in patients with RA and determine its reliability, robustness, safety, local tolerance, and ease of use.
  
  
  METHODS
  In this phase 2, multicenter, open-label, single-dose, single-arm, in-clinic US study, adults (N = 101) treated with methotrexate for 3 months or longer were trained to use the MTXAI and assigned to 10, 15, 20, or 25 mg methotrexate based on previous treatment and disease status. Patients completed training confirmation and ease-of-use questionnaires. Pain was evaluated immediately after self-administration and at follow-up with a 100-mm visual analog scale (0 = no pain, 100 = worst possible pain).
  
  
  RESULTS
  At screening, 90.1% of patients had moderate to severe functional limitations (class II-IV). All patients successfully completed the study. All devices functioned correctly and as intended. The device was rated easy to use by 98%, and instructions clear and easy to follow by 100% of patients. On the visual analog scale, mean and median pain scores were 3.6/100 and 1.0/100 mm, respectively, immediately after self-administration, and were lower at follow-up. Most patients (92.3%) had no administration-site erythema; 7.7% had minimal erythema.
  
  
  CONCLUSIONS
  The SC MTXAI was well tolerated and considered easy to use by patients with RA. Improving SC methotrexate delivery may increase patient tolerance of self-administration, possibly improving adherence.
authors.affiliation: From the *University of Pennsylvania, Philadelphia, PA; †Antares Pharma, Inc, Ewing, NJ; and ‡Altoona Center for Clinical Research, Duncansville, PA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Freundlich
authors.forename: Alan
authors.initials: A
authors.lastname: Kivitz
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Jaffe
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004867:Equipment Design; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D020714:Maximum Tolerated Dose; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D010147:Pain Measurement; D012646:Self Administration / Q000295:instrumentation / Q000379:methods; D012720:Severity of Illness Index; D013594:Syringes; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate