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Abstract
Objectives Evaluate long-term efficacy of IV GLM 2mg/kg+MTX in active RAdespite MTX thru wk52.
Methods Pts(n=592)with active RA(≥6/66 SJ,≥6/68TJ, CRP≥1.0mg/dL, RF&/or anti-CCP+at screen)despite ≥3mo of MTX(15-25mg/wk)participated. Pts rand to IV GLM2mg/kgorPBO at wks0&4 &q8wks;all pts cont’d stable MTX. Pts rand to PBO with<10% improve’t in SJ+TJ cts atwk16 could EE to IV GLM2mg/kg(wks16&20, q8wks). All PBO pts rec’d IV GLM2mg/kg starting atwk24. Primary endpt was wk14 ACR20. Radiographs of hands&feet at baseline(BL), wk24(wk16 for EE)& wk52 were scored by 2independent readers&adjudicator(asneeded)using modified vdHS score.
Results 93% of pts(553/592)cont’d thru wk52;39 pts d/c, mostly due to AEs(18 pts). At wk14, sig (p<0.001)larger propor of GLM+MTXvsPBO+MTX pts achieved ACR20,50,70, DAS28-CRP good/mod responses,&greater median improv’t in HAQ(0.50vs0.13). Among pts who achieved ACR20,50,70,& DAS28 good/mod by wk24, 82%,72%,61%,&88%, resp, maintained response thru wk52. At wk52, ACR20,50,70 for GLM&PBO grps were: 65.8%,38.7%,18.2%,& 61.4%,31.5%,14.7%. DAS28-CRP mod/good were 81.3%&75.6% for GLMvsPBO grp. Median improv’t from BL HAQ were:0.51±0.65 & 0.42±0.59 for GLMvsPBO grp; improve’ts in HAQ≥0.25 fromBL:64.1%&62.4% of pts, resp. GLM+MTX-tx pts showed sig less radiographic progression(RP)(total vdHS+subscores)vs PBO+MTX at wk24. Pts rand to PBO+MTX who began GLM at wk16/24 showed marked slowing of RP same rate as pts rand to GLM, from wk24towk52. Thru wk52, all GLM-tx pts were followed an avg of 44wks. AEs& SAEs occurred in 65%&9%, resp, of GLM-tx pts(vs 43%&4% at wk24).1 case of TB &no serious opportunistic infect’s were reported thru wk52.1 pt receiving GLM+MTX (0.16%)died. Thru wk52, propor of inf &pts with inf reactions were 0.7% &3.6%, resp,(vs 1.1%&3.5% at wk24).
Conclusions GLM+MTX sig inhibited RP(for total vdHS&subscores)at wk24&52. Among PBO-tx pts who began GLM at wk16/wk24, marked slowing of RP, to the rate in pts rand to GLM, was observed from wk24towk52. IV GLM+MTX sig improv’d&maintained RA signs&sx in active RA despite ongoing MTX&cont’d to show acceptable safety profile thru wk52.
Disclosure of Interest M. Weinblatt Grant/research support from: Janssen R&D, LLC, C. O. Bingham III Grant/research support from: Janssen R&D, LLC, A. Mendelsohn Employee of: Janssen R&D, LLC, L. Noonan Employee of: Janssen R&D, LLC, S. Sheng Employee of: Janssen R&D, LLC, L. Kim Employee of: Janssen R&D, LLC, K. Hung Employee of: Janssen R&D, LLC, J. Lu Employee of: Janssen R&D, LLC, D. Baker Employee of: Janssen R&D, LLC, R. Westhovens Grant/research support from: Janssen R&D, LLC