Objectives To describe the safety profile of IV GLM in RA (MTX nonresponders) from the Ph3 GO-FURTHER trial. AE rates of interest are indirectly compared to those observed in the SC GLM GO-FORWARD trial in a similar pt population.
Methods In GO-FURTHER, pts with active RA despite MTX were randomized to MTX + IV PBO or GLM 2mg/kg at wks 0, 4, and q8wks. In GO-FORWARD, pts with active RA despite MTX were randomized to SC PBO+MTX or SC GLM 100mg+PBO, GLM 50 mg+MTX, or GLM 100 mg+MTX administered q4wks. Observed safety findings through wk 112 for GO-FURTHER and wk 104 in GO-FORWARD are reported; incidence rates/100 pt-yrs are reported for AEs of interest from data through the August 15, 2012 cut-off (120-day safety update) in GO-FURTHER and from the wk160 CSR in GO-FORWARD. Comparison of targeted safety events between IV and SC GLM are reported. Pts who received ≥1 administration were included.
Results Baseline demographic and disease characteristics were similar in GO-FURTHER and GO-FORWARD. 584 pts received IV GLM, with a mean follow-up of 95.9 wks. 434 pts received SC GLM, with a mean follow-up of 89.9 wks. Overall AEs observed in GO-FURTHER and GO-FORWARD are summarized (Table). Similar proportions of pts in GO-FURTHER (wk 112) and GO-FORWARD (wk 104) had an AE (79.1% and 89.4%, respectively), an SAE (18.2% and 22.6%, respectively), or discontinued due to an AE (7.0% and 9.4%, respectively). Infections/infestations were the most common type of AE in both trials. Rates of selected SAEs per 100 pt-years through the August 15, 2012 cut-off in GO-FURTHER and wk 160 in GO-FORWARD showed no difference in AE rates or significant SAEs between GLM IV and SC in RA pts previously treated with MTX with the exception of patients with ALT abnormalities (>1 - <3 x ULN). Similar differences were noted through all ALT tertiles (≥3 - <5 x ULN; ≥5 x ULN) (Table). Incidence of nonserious infusion reactions (median 30 minute infusions) remained low regardless of infusion length, and no serious infusion reactions, requiring study discontinuation, were reported. NMSC (incidence/100 pt-yrs of f/u: 0.10[95% CI: 0.00,0.58] vs. 0.81 [95%CI: 0.37,1.54] for GLM IV vs GLM SC) and lymphoma rates were numerically lower in GO-FURTHER vs. GO-FORWARD.
Conclusions Overall safety profile of IV GLM in pts with RA despite MTX observed through wk 112 in GO-FURTHER was similar to that for SC GLM in a similar pt population (GO-FORWARD). Rates/100 pt-yrs (through August 15, 2012 in GO-FURTHER and wk 160 in GO-FORWARD) for events of interest such as malignancies and serious infections in GO-FURTHER were comparable to or lower than rates in GO-FORWARD.
Disclosure of Interest R. Westhovens Grant/research support from: Janssen R & D, LLC, E. Keystone Grant/research support from: Janssen R & D, LLC, C. Bingham Grant/research support from: Janssen R & D, LLC, E. Hsia Employee of: Janssen R & D, LLC, L. Kim Employee of: Janssen R & D, LLC, Y. Zhou Employee of: Janssen R & D, LLC, A. Mendelsohn Employee of: Janssen R & D, LLC, M. Weinblatt Grant/research support from: Janssen R & D, LLC