title: Change from subcutaneous to intravenous abatacept and back in patients with rheumatoid arthritis as simulation of a vacation: a prospective phase IV, open-label trial (A-BREAK).
abstract: BACKGROUND
  Vacation can present a major problem to patients with rheumatoid arthritis (RA) treated with weekly subcutaneous biologics, including subcutaneous (SC) abatacept. Therefore, the replacement of four SC doses of abatacept by a single dose of intravenous (IV) abatacept may present an acceptable alternative to cover a 4-week interval needed for vacations. In the study presented, we analyzed the efficacy and safety of this intervention followed by a switch back to SC abatacept after 4 weeks.
  
  
  METHODS
  This open-label, prospective, single-arm, 24-week trial recruited patients with established RA in low disease activity (LDA) or in remission on treatment with SC abatacept for at least 3 months to receive a single dose of IV abatacept (baseline) followed by a break of 4 weeks and then continuation of weekly SC abatacept from day 28 on. Disease-modifying anti-rheumatic drug (DMARD)-inadequate or biologic-inadequate responders (or both) were included.
  
  
  RESULTS
  The baseline characteristics of the 49 patients (per protocol) were typical for a cohort of RA patients with established disease (mean disease duration of 8.31 years) in LDA under treatment with synthetic DMARDs and a biologic. Two patients (one flare and one patient decision) dropped out of the study. The proportions of patients with disease activity score in 28 joints (DAS-28) of not more than 3.2 at day 28 were 93.9 % (95 % confidence interval (CI) 83.5-97.9) and 93.6 % (95 % CI 82.8-97.8) at the end of the study (day 168). The average DAS-28 values were 1.74 (standard deviation (SD) ± 0.72) at baseline, 2.03 (SD ± 1.03) at day 28, and 1.96 (SD ± 0.92) at the end of the study (day 168). Pre-exposure to IV abatacept and having failed methotrexate or anti-tumor necrosis factor (anti-TNF) did not influence the average DAS-28 or the proportion of patients maintaining LDA over time. The average health assessment questionnaire disability index (HAQ-DI) was stable throughout the study. Adverse events (AEs) occurred in 75 % of subjects. Four serious AEs were described during the study. None of them was related to the investigational product, and all serious AEs could be resolved during hospitalization.
  
  
  CONCLUSIONS
  This prospective, open-label study of abatacept shows for the first time that switching from weekly SC to IV abatacept and back after 4 weeks is an effective and safe way to bridge vacations in RA patients in LDA or remission. (NCT1846975, registered April 19, 2013.).
authors.affiliation: Division of Rheumatology, Immunology and Rehabilitation, Kantonsspital St. Gallen, Rorschacherstr. 95, 9007, St. Gallen, Switzerland. ruediger.mueller@kssg.ch.
authors.forename: Ruediger B
authors.initials: RB
authors.lastname: Mueller
authors.affiliation: Bethesdaspital, Gellertstrasse 144, 4052, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Gengenbacher
authors.affiliation: Bethesdaspital, Gellertstrasse 144, 4052, Basel, Switzerland.
authors.forename: Symi
authors.initials: S
authors.lastname: Richter
authors.affiliation: Kantonsspital Fribourg, Chemin des Pensionnats 2, 1708, Fribourg, Switzerland.
authors.forename: Jean
authors.initials: J
authors.lastname: Dudler
authors.affiliation: Inselspital, Sahlihaus 2, 3010, Bern, Switzerland.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Möller
authors.affiliation: Division of Rheumatology, Immunology and Rehabilitation, Kantonsspital St. Gallen, Rorschacherstr. 95, 9007, St. Gallen, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: von Kempis
mesh_terms: D000069594:Abatacept / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D018501:Antirheumatic Agents; D000069594:Abatacept
keywords: Abatacept; Intravenous; LDA; Subcutaneous; Switch