ObjectiveEvaluate ustekinumab, an anti-interleukin (IL)-12 and IL-23 antibody, effects on radiographic progression in psoriatic arthritis (PsA).MethodsWe conducted preplanned integrated analyses of combined radiographic data from PSUMMIT-1 and PSUMMIT-2 phase 3, randomised, controlled trials. Patients had active PsA despite prior conventional and/or biologic disease-modifying antirheumatic drugs (≥5/66 swollen, ≥5/68 tender joints, C-reactive protein ≥3.0 mg/L, documented plaque psoriasis). Patients (PSUMMIT-1, n=615; PSUMMIT-2, n=312) were randomised to ustekinumab 45 mg, 90 mg, or placebo, at weeks (wk) 0, 4 and every (q) 12 wks. At wk 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape. All other placebo patients received ustekinumab 45 mg at wk 24 and wk 28, then q 12 wks. Radiographs of hands/feet at wks 0/24/52 were assessed using PsA-modified van der Heijde-Sharp (vdH-S) scores; combined PSUMMIT-1 and PSUMMIT-2 changes in total vdH-S scores from wk 0 to wk 24 comprised the prespecified primary radiographic analysis. Treatment effects were assessed using analysis of variance on van der Waerden normal scores (factors=treatment, baseline methotrexate usage, and study).ResultsIntegrated data analysis results indicated that ustekinumab-treated patients (regardless of dose) demonstrated significantly less radiographic progression at wk 24 than did placebo recipients (wk 0–24 total vdH-S score mean changes: 0.4-combined/individual ustekinumab dose groups, 1.0-placebo; all p<0.02). From wk 24 to wk 52, inhibition of radiographic progression was maintained for ustekinumab-treated patients, and progression was substantially reduced among initial placebo recipients who started ustekinumab at wk 16 or wk 24 (wk 24 – wk 52, total vdH-S score mean change: 0.08).ConclusionsUstekinumab 45 and 90 mg treatments significantly inhibited radiographic progression of joint damage in patients with active PsA.

Objective Report on radiographic effects and maintenance of clinical benefit with intravenous golimumab 2 mg/kg+methotrexate (MTX) for up to week (wk) 52 in active rheumatoid arthritis (RA). Methods Patients (n=592) with active RA (≥6/66 swollen, ≥6/68 tender joints, C reactive protein (CRP) ≥1.0 mg/dL and positive for rheumatoid factor and/or anticyclic citrullinated protein antibody at screening) despite MTX ≥3 months (stable dose of 15–25 mg/week for ≥4 weeks) participated in this multicentre, international, randomised, double blind, placebo controlled, phase 3 study. Patients were randomised (2:1) to receive intravenous golimumab 2 mg/kg or placebo infusions at weeks 0 and 4 and then every 8 weeks; patients continued their stable MTX regimen. Placebo patients started golimumab 2 mg/kg at wk16 (early escape; <10% improvement in tender and swollen joints) or wk24 (crossover by design). Week 24 and wk52 radiographic (van der Heijde-Sharp (vdH-S) scores), clinical efficacy and safety data up to 1 year are reported here. Results Significant and rapid clinical improvement was observed up to wk24 of intravenous golimumab therapy. Golimumab+MTX treated patients demonstrated less radiographic progression than placebo treated patients at wk24 (vdH-S score mean change 0.03 vs 1.09; p<0.001) and wk52 (0.13 vs 1.22; p=0.001). Among patients with ≥20% improvement in the American College of Rheumatology response criteria or who achieved a ‘good’ or ‘moderate’ response according to the 28 joint Disease Activity Score employing CRP at wk24, approximately 80% maintained this response up until wk52. Through an average of 43.5 weeks of follow-up, 64.6% of patients receiving golimumab+MTX reported adverse events, most commonly non-serious infections. Conclusions In patients with active RA despite MTX, intravenous golimumab+MTX yielded significant inhibition of structural damage at wk24 and wk52, and sustained clinical improvement in signs and symptoms with no new safety signals up to 1 year. ClinicalTrials.gov NCT00973479, EudraCT 2008–006 064–11.

Objective.Evaluate effects of intravenous (IV) golimumab (GOL) on radiographic progression in psoriatic arthritis (PsA).Methods.This phase III, randomized, double-blind, placebo-controlled trial (GO-VIBRANT) randomized patients with active PsA to receive IV placebo (n = 239) or IV GOL 2 mg/kg (n = 241) at weeks 0, 4, 12, and 20. Radiographic progression (controlled secondary endpoint) was evaluated as change from baseline at Week 24 in PsA-modified total Sharp/van der Heijde scores (SvdH). The proportions of patients with a change from baseline at Week 24 in the total PsA-modified SvdH exceeding the smallest detectable change (SDC) or > 0 or 0.5 also were determined.Results.Overall, 474 patients (237/arm) contributed radiographic data. Results obtained from the 2 blinded, independent radiographic readers demonstrated good agreement (total score intraclass correlation coefficients: baseline = 0.93, Week 24 = 0.92, Week 24 change score = 0.73). GOL demonstrated significant inhibition of radiographic progression relative to placebo from baseline to Week 24 (mean changes in PsA-modified total SvdH: −0.36 vs 1.95; treatment difference: −2.32; p < 0.001). At Week 24, smaller proportions of GOL- versus placebo-treated patients demonstrated an increase in the total PsA-modified SvdH score exceeding the SDC (8.0% vs 27.0%, respectively; difference: −19.0%; p < 0.001), > 0 (28.3% vs 57.0%, respectively; difference: −28.7%; p < 0.001), or > 0.5 (18.6% vs 41.8%, respectively; difference: −23.2%; p < 0.001). Results were consistent for erosion and joint space narrowing scores, in hands and feet, and in patients with/without baseline concomitant methotrexate use. Prevention of radiographic progression by GOL was independent of clinical response.Conclusion.IV GOL is significantly better than placebo in inhibiting radiographic progression of structural damage in active PsA. [Clinical trial registration number (www.ClinicalTrials.gov): NCT02181673]

Objectives Safety, efficacy, & radiographic progression in GLM-treated pts from long-term extension of GO-REVEAL is presented. Methods 405 PsA pts (≥3 SJ, ≥3 TJ counts) were rand to SC PBO (Grp1, n=113), GLM50mg (Grp2, n=146), or GLM100mg (Grp3, n=146) q4wks thru wk20. Concomitant MTX at baseline (BL) was allowed but not required. At wk16, pts with <10% improvement in SJ&TJ were eligible for rescue tx. All pts received GLM from wk24 forward. After wk52, pts could change GLM dose based on investigator judgment. The last GLM inj was at wk252; efficacy was assessed at wk256 based on rand grp&completer analyses using ACR response criteria, DAS28-CRP, PASI, HAQ, enthesitis/dactylitis assessments, NAPSI scores, & PsA-modified Sharp/van der Heijde Score (SHS). Safety evaluations included all pts who received at least one GLM dose thru 5yrs. Results Of 405 pts rand, 335 cont’d in the study at wk104, & 279 pts (69%) cont’d GLM thru wk252. 29% of Grp2 pts dose escalated to GLM100mg; 25% of Grp3 pts decreased dose from 100mg to 50mg. BL characteristics of pts who cont’d in the study at wk104 & efficacy at wk256 are provided(Table). ACR&PASI responses were similar in pts tx with or without MTX; changes from BL in SHS scores were minimal&numerically less in pts tx with GLM & MTXvs GLM alone. 88%, & 21% GLM-tx pts experienced AE & SAE, resp. 12% of pts d/c GLM due to AE, & 5% & 4% pts experienced malignancy (incl NMSC),& serious infection, resp. Antibodies to GLM were detected in 6% of pts. Conclusions Pt attrition thru 5yrs of GLM tx was low. GLM tx resulted in long-term maintenance of clinically meaningful responses in arthritic & skin components of PsA, improved physical function, & arrest of radiographic progression. No apparent differences between long-term safety&efficacy of 2 GLM doses administered q4wks were observed, however, interpretation of the data is limited due to tx changes allowed across rand grps. Disclosure of Interest A. Kavanaugh Grant/research support from: Janssen Research and Development, LLC, D. van der Heijde Grant/research support from: Janssen Research and Development, LLC, I. McInnes Grant/research support from: Janssen Research and Development, LLC, P. Mease Grant/research support from: Janssen Research and Development, LLC, G. G. Krueger Grant/research support from: Janssen Research and Development, LLC, D. Gladman Grant/research support from: Janssen Research and Development, LLC, Y. Zhou Employee of: Janssen Research and Development, LLC, J. D. Lu Employee of: Janssen Research and Development, LLC, Z. Xu Employee of: Janssen Research and Development, LLC, L. Noonan Employee of: Janssen Research and Development, LLC, A. Beutler Employee of: Janssen Research and Development, LLC

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