Background: The GO-ALIVE study assessed efficacy and safety of intravenous golimumab (IV GLM) in patients (pts) with ankylosing spondylitis (AS).1,2 Objectives: In this post hoc analysis, we assessed IV GLM efficacy and safety in AS pts with early disease (ED) vs late disease (LD) based on pt-reported duration of inflammatory back pain (IBP). Methods: In this Phase 3, double-blind, placebo (PBO)-controlled trial, pts with active AS were randomized (1:1) to receive IV GLM 2 mg/kg at Week (W) 0, W4, then Q8W or PBO at W0, W4, and W12 with crossover to IV GLM at W16, W20, then Q8W through 52. The primary endpoint was achievement of SpondyloArthritis International Society 20% improvement response (ASAS 20) at W16. In this post hoc analysis, 208 pts were grouped into quartiles based on self-reported duration of IBP symptoms. Efficacy and safety in 60 pts with ED (1st quartile) were compared with 52 pts with LD (4th quartile). Results: For the overall study population, mean duration of IBP symptoms was 10.9 yr and mean time since diagnosis was 5.5 yr. For ED pts, the mean duration of IBP symptoms ranged from 2.3 yr (IV GLM) to 2.6 yr (PBO), and for LD pts ranged from 23.5 yr (IV GLM) to 24.4 yr (PBO). At W16, ASAS 20 was achieved by 72% IV GLM vs 32% PBO pts with ED and by 67% IV GLM vs 21% PBO pts with LD. Pts with ED had numerically better response than those with LD in Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), and across more stringent endpoints, including ASAS 40, Bath Ankylosing Spondylitis Disease Activity Index 50% improvement (BASDAI 50), and Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease and major improvement (Table 1). Response rates at W16 among IV GLM-treated pts were generally consistent through 1 year in both ED and LD subgroups; also in ED and LD subgroups, pts crossing over to IV GLM at W16 demonstrated response at W52 consistent with pts who started IV GLM at W0. At W16, improvements in enthesitis score were similar for pts with ED (mean change -2.9 for IV GLM vs 0.1 for PBO) and LD (mean change -2.5 for IV GLM vs 0.6 for PBO); improvements were maintained at W52 for ED and LD pts. Treatment-emergent adverse events and serious adverse events through 1 year were 46% and 3% for pts with ED compared with 61% and 2% for pts with LD, respectively. Conclusion: While IV GLM provided clinically meaningful improvements in signs and symptoms of AS in pts regardless of disease duration, response generally appeared numerically better in pts with ED than in pts with LD. This supports the principle of prompt diagnosis and early treatment.S.

Background: Final 5-year safety and efficacy results of s.c. golimumab (GLM)+/-MTX evaluated in a phase 3 trial (GO-BEFORE) of MTX-naïve pts with RA are reported. Methods: Pts in GO-BEFORE were randomized to placebo(PBO)+MTX, GLM 100mg+PBO, GLM 50mg+MTX, or GLM 100mg+MTX q4w. PBO+MTX pts crossed over to GLM+MTX at weeks 28 (blinded early escape) or 52 (pts with ≥1 swollen/tender joint). Pts continued treatment at week 52 (start of longterm extension). After the last pt completed week 52 and unblinding occurred, PBO+MTX pts could switch to GLM 50mg+MTX, MTX and corticosteroid use could be adjusted, and a one-time GLM dose change (50 to 100mg or 100 to 50 mg) was permitted at investigator's discretion. The last GLM injection was at week 252. Observed efficacy results (ACR20/50/70, DAS28-CRP, HAQ-DI, radiographic) by randomized treatment group and cumulative safety data are reported through weeks 256 and 268, respectively. Results: Of 637 randomized pts, 3 were never treated; 419 continued treatment through week 252, and 215 pts withdrew (111 for AE, 23 for lack of efficacy, 20 lost to follow-up, 53 for other reasons, 8 deaths). 402 pts completed the safety follow-up through week 268. At week 256, 84.3% of all pts had an ACR20, 93.9% had DAS28-CRP EULAR response, and 80.6% had improvement in HAQ-DI ≥0.25. Mean changes from baseline in total vdH-S score were small and 64% of pts randomized to GLM+MTX had no radiographic progression (ΔvdHS ≤0). The most common AEs were upper respiratory tract infection (29.4%), nausea (19.6%), bronchitis (16.6%), and increased alanine aminotransferase (16.1%); 11.9% of pts had an injection-site reaction. Through week 268, 204/616 (33.1%) pts had an SAE; 17.5% of pts discontinued study agent due to AEs. Overall rates of serious infections, malignancies, and death were 12.2%, 3.4%, and 1.9%, respectively. Of 595 pts with available samples, 58 (9.7%) were positive for antibodies to GLM. Conclusion: The retention rate was high (66.1%) through 5 years. GLM+MTX therapy resulted in maintained improvements in signs/ symptoms of RA and in physical function, and inhibited structural damage progression long-term. No new safety signals were detected through 5years in MTX-naïve RA pts.

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Background: GO-VIBRANT is a Phase 3 trial of intravenous (IV) golimumab (GLM), an anti-tumor necrosis factor alpha (TNFα) monoclonal antibody, in adult patients (pts) with active psoriatic arthritis (PsA). Objectives: To assess if changes in Disease Activity in PsA (DAPSA), PsA Activity Score (PASDAS), Minimal Disease Activity (MDA), Very Low Disease Activity (VLDA), and Clinical Disease Activity Index (CDAI) measures correlate with X-ray progression. Methods: In this multicenter, randomized, double-blind, placebo (PBO)-controlled trial, 480 bionaïve PsA pts with active disease (≥5 swollen & ≥5 tender joints, C-reactive protein ≥0.6mg/dL, active plaque psoriasis or documented history despite treatment w/csDMARDs & /or NSAIDs) received IV GLM 2mg/kg (N=241) at Wks0/4 then q8wks or PBO (N=239) at Wks0/4/12/20 with crossover to GLM at Wk24. In a post-hoc analysis, association of disease activity measures DAPSA, PASDAS, MDA, VLDA, & CDAI with X-ray progression was examined. Total modified van der Heijde-Sharp (vdH-S) score assessed X-ray progression at Wks 0/24/52. Last observation carried forward imputation was used for partially missing data & non-responder imputation for missing data. Nominal p-values are reported without multiplicity adjustment. Results: Mean changes from baseline in vdH-S scores were lower with GLM than PBO at Wk24 (-0.36 vs 1.95, respectively, p<0.001) and at Wk52 after crossover from PBO to GLM arm (-0.49 vs 0.76). Changes in all disease activity measures appeared to correlate with X-ray progression (Table). GLM-treated pts had less X-ray progression regardless of disease activity measure. GLM treated pts in remission or with low disease activity tended to have less X-ray progression at Wk52 vs pts with moderate or high disease activity (mean change in vd

H-S:

DAPSA remission or low disease activity-0.88, moderate activity-0.48, high disease activity 0.41). Similar patterns were seen with PASDAS and CDAI (Table). Irrespective of level of disease activity, GLM-treated pts from Wk 0-52 tended to have less X-ray progression vs PBOtreated pts who switched to GLM at Wk24 (mean change in vdH-S 0-52 wk GLM vs PBO→

GLM:

DAPSA remission or low disease activity-0.88 vs 1.49, moderate activity-0.48 vs 1.38, high disease activity 0.41 vs 1.27). Interestingly, pts treated with GLM who did not achieve MDA or VLDA by Wk52 also tended to have less X-ray progression vs PBO pts (mean change no MDA GLM 0.03 vs PBO 1.50; p=0.0011 and mean change no VLDA GLM-0.30 vs PBO 1.45; p<0.0001). Conclusion: In this analysis, all disease activity measures generally correlated with X-ray progression from baseline to Wk24 and to Wk52. Higher disease activity was associated with increased X-ray progression. GLM-treated pts not achieving MDA & VLDA at Wk52 tended to have less Xray progression vs PBO→GLM pts. GLM's ability to inhibit X-ray progression, despite pts not being in clinical remission or low disease activity, illustrates an example of “disconnect” between clinical outcomes & X-ray progression seen in other studies. (Table Presented) .

Objectives: To evaluate the efficacy and safety of golimumab in patients with active peripheral Spondyloarthritis (pSpA) in a very early stage of the disease. Methods: CRESPA (Clinical REmission in peripheral SPondyloArthritis) is an ongoing monocentric study of golimumab treatment in pSpA patients. Eligible patients were ≥18 years and fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for pSpA. All patients had a symptom duration of less than 3 months. Patients were randomized 2:1 to receive golimumab 50 mg every 4 weeks or matching placebo for 24 weeks. The primary endpoint was the percentage of patients achieving clinical remission at week 24. Clinical remission was defined as the absence of arthritis, enthesitis and dactylitis on clinical examination. From week 12 onwards, there was an option to start rescue medication with golimumab 50 mg SC every 4 weeks. Adverse events were recorded throughout the study. Results: In total 60 patients were randomized of whom 20 to the placebo group and 40 to the golimumab group. Baseline demographics and disease characteristics were generally similar between the 2 groups. At week 24 a significant higher percentage of patients receiving golimumab achieved clinical remission compared to patients receiving placebo (75% (30/40) versus 20% (4/20); P<0.001). At week 12 similar results were observed (70% (28/40) versus 15% (3/20); P<0.001). Overall, improvement in other outcomes was significantly greater in the golimumab group compared to the placebo group (table 1). In the placebo group 10 out of 20 patients (50%) entered the rescue arm, compared to only 4 of 40 (10%) patients in the golimumab arm. The rates of adverse events were very low and similar in both treatment groups. Conclusions: In patients with active, very early peripheral spondyloarthritis, treatment with golimumab led to high percentages of clinical remission and significant improvement in all secondary efficacy outcomes, compared to placebo, with a safety profile consistent with that observed in anti-TNF trials with ankylosing spondylitis and psoriatic arthritis patients. (Table Presented).

INTRODUCTION/OBJECTIVES:

To evaluate changes in health-related quality of life (HRQoL) and productivity following treatment with intravenous (IV) golimumab in patients with psoriatic arthritis (PsA).

METHODS:

Patients were randomized to IV golimumab 2 mg/kg (n=241) at Weeks 0, 4, then every 8 weeks (q8w) through Week 52 or placebo (n=239) at Weeks 0, 4, then q8w, with crossover to IV golimumab 2 mg/kg at Weeks 24, 28, then q8w through Week 52. Change from baseline in EuroQol-5 dimension-5 level (EQ-5D-5L) index and visual analog scale (EQ-VAS), daily productivity VAS, and the Work Limitations Questionnaire (WLQ) was assessed. Relationships between these outcomes and disease activity and patient functional capability were evaluated post hoc.

RESULTS:

At Week 8, change from baseline in EQ-5D-5L index (0.14 vs 0.04), EQ-VAS (17.16 vs 3.69), daily productivity VAS (-2.91 vs -0.71), and WLQ productivity loss score (-2.92 vs -0.78) was greater in the golimumab group versus the placebo group, respectively. At Week 52, change from baseline was similar in the golimumab and placebo-crossover groups (EQ-5D-5L index: 0.17 and 0.15;

EQ-VAS:

21.61 and 20.84; daily productivity

VAS:

-2.89 and -3.31; WLQ productivity loss: -4.49 and -3.28, respectively). HRQoL and productivity were generally associated with disease activity and functional capability, with continued association from Week 8 through Week 52.

CONCLUSION:

IV golimumab resulted in early and sustained improvements in HRQoL and productivity from Week 8 through 1 year in patients with PsA. HRQoL and productivity improvements were associated with improvements in disease activity and patient functional capability. Key Points • In patients with active psoriatic arthritis (PsA), intravenous (IV) golimumab improved health-related quality of life (HRQoL) and productivity as early as 8 weeks and maintained improvement through 1 year • Improvements in HRQoL and productivity outcomes in patients with PsA treated with IV golimumab were associated with improvements in disease activity and patient functional capability outcomes • IV golimumab is an effective treatment option for PsA that can mitigate the negative effects of the disease on HRQoL and productivity.

OBJECTIVE:

Reactivation of Mycobacterium tuberculosis infection is a major complication in patients treated with anti-tumor necrosis factor (anti-TNF) agents. We report on the 5 cases of active tuberculosis (TB) that developed in the Golimumab Phase III Program (3 with rheumatoid arthritis, 1 with psoriatic arthritis, and 1 with ankylosing spondylitis) through 1 year among 2,210 patients receiving golimumab.

METHODS:

Data from global studies were used for an in-depth evaluation of the 5 cases of TB through week 52. Integrated safety data were evaluated for potential hepatotoxicity in patients treated with anti-TB therapy.

RESULTS:

No active TB developed among 317 patients receiving golimumab and treated for latent TB with isoniazid. Active TB occurred in 5 patients not treated with isoniazid by week 52 (in 2 patients by week 24); all of the patients had negative TB screening tests (per the local guidelines) and resided in countries with high background rates of TB. No deaths were due to TB. Across all of the groups (placebo and golimumab), alanine aminotransferase and aspartate aminotransferase elevations occurred in greater proportions of patients treated for latent TB infection versus not treated; elevations were largely mild (<3 times the upper limit of normal).

CONCLUSION:

Comprehensive TB screening kept the number of active TB cases relatively low despite conducting the studies in TB-endemic regions. Treatment for latent TB infection appeared effective, since no patients treated for latent TB had TB reactivation. Concurrent treatment with golimumab and anti-TB medication was generally well tolerated. Clinicians should remain vigilant for development of active TB after initiation of TNF inhibitors, since prompt diagnosis and treatment can improve outcomes.

Objectives: AWARE (Comparative and Pragmatic Study of Golimumab IV Versus Infliximab in Rheumatoid Arthritis) is a Phase 4, prospective, noninterventional, observational, multicenter (88 sites), 3-year US study providing real-world assessment of intravenous golimumab (GLM) and infliximab (IFX) in patients with rheumatoid arthritis. Treatment decisions, including prescribed dose and dosing interval, are made by the treating rheumatologists. This analysis of 52-week results from AWARE explored patterns of dose escalation (DE) among IFX patients and compared changes in Clinical Disease Activity Index (CDAI), comparing IFX and GLM. Methods: AWARE enrolled patients initiating GLM or IFX treatment. Prescribed dosewas recorded at the time of infusion. Patients had DEwhen ≥1 normalized prescribed dose exceeded the baseline dose. Normalized prescribed dose = ([prescribed dose] x [scheduled time interval]/[actual time interval]). CDAI was determined at baseline and Months 3, 6, and 12. Results: Baseline demographics were generally similar between 685 GLMand 585 IFX patients (including 425 DE IFX patients), although mean ± SD disease duration was 9.20 ± 9.97 years for GLM and 6.87 ± 9.28 years for DE IFX patients. Among bionaïve and non-bionaïve GLMpatients with an imputed CDAI measure, the mean prescribed dose was 2.0 mg/kg from infusion 1 through 9. The mean normalized prescribed dose among bionaïve DE IFX patients with CDAI data as 3.25 mg/kg and increased at each infusion through infusion 9 (5.14 mg/kg). The mean normalized prescribed dose among non-bionaïve DE IFX patients with CDAI data was 3.29 mg/kg and increased at each infusion through infusion 9 (5.48 mg/kg). Based on the definition of normalized dose, 75.9% of all IFX patients were DE (72.4% of bionaïve IFX and 78.7% of non-bionaïve IFX patients). The % of bionaïve IFX patients prescribed at least 1 dose ≥8 mg/kg increased with each infusion through infusion 12. At the 10th and 12th infusions, respectively, 15.1% (39/238) and 19.1% (36/188) of IFX patients had received at least 1 IFX dose ≥8 mg/kg. Conclusions: The majority of IFX patients were dose escalated, evident in the increasing mean normalized dose and the proportion of patients prescribed at least 1 IFX dose ≥8 mg/kg. The mean changes from baseline in CDAI scores were similar between GLMpatients and DE IFX patients, although numerically lower for non-DE IFX patients.

OBJECTIVES:

To evaluate IV golimumab(GLM) on HRQol and work productivity in RA.

METHODS:

Patients with active RA despite MTX(>6TJC&SJC,CRP>1.0mg/ dL,and RF and/or anti-CCP+) were randomized to placebo+MTX(placebo group) or GLM2mg/kg+MTX(GLM group) at wk0,2,and q8wk,thereafter.Patients in placebo group with<10% improvement in TJC&SJC from baseline at wk16 entered early escape and received IV GLM2mg/kg infusion at wks16 and 20 and q8wks,thereafter.HRQol was assessed using SF-36 and EQ5D(five-item descriptive system of health states and a visual analog scale[EQ VAS,0-100]).Scores for the five health states were converted into a utility score(EQ5D index,0- 1,0=dead,1=full health)using the US D1 model.Impact of disease on daily work productivity was assessed using VAS 0-10(0=no affect,10=affected very much- ).Clinically meaningful improvements were defined as change of=5 points in SF-36 PCS and MCS or a change in magnitude of half of standard deviation in EQVAS and EQ5D index.Correlation of remission measured by DAS28(using CRp<2.6) with change in PCS and MCS,and productivity scores were analyzed- .Comparisons performed using ANOVA on van der Waerden normal scores for continuous outcomes or Chi-square test for binary outcomes.

RESULTS:

At baseline, mean(SD)SF-36 PCS(30.8±6.95)andMCS(37.6±11.28)were below the US norm(50).Impact of disease on daily work productivity was 6.4(2.32).Compared to placebo,significantly greater changes were observed in the GLM-treatment group inSF-36 PCS(5.92vs3.19),SF-36MCS(4.91vs1.46),EQVAS scores(11.43vs2.53) and EQ5D index(0.13 vs0.09) at wk12,which were sustained through wk16 and 24(pvalues <0.01).Compared to placebo,a greater proportion of patients in the GLM group achieved clinically meaningful improvement in SF-36PCS,SF36MCS,EQVAS and EQ5Dindex.Significantly greater improvements in 8 SF-36 sub-scores for the GLM group vs placebo,were observed(p< 0.001).At wk24,mean change(improvement) from baseline in impact of disease on daily work productivity was significantly better in GLM group vs placebo(-2.78vs-1.03,p<0.001).Change in SF-36 and work productivity were correlated with change in DAS28,and those who achieved DAS28 remission had greater improvement in SF-36 PCS,MCS and productivity VAS scores than those who didn't achieve remission.

CONCLUSIONS:

IV GLM significantly improved HRQol and work productivity in RA.

Background and aim: Adalimumab (ADA) and Golimumab (GOL) are effective in the treatment of moderate to severe ulcerative colitis (UC). Material and methods: The Sicilian Network for Inflammatory Bowel Disease (SN-IBD) is a group composed by all Sicilian centres prescribing biologics. We extracted web-based data from the SN-IBD to perform a real life observational study on the comparative effectiveness of ADA and GOL in UC patients. 197 consecutive patients with moderate to severe UC were treated with ADA or GOL. The effectiveness was evaluated at 8 weeks and at the end of follow up. We defined “steroid-free clinical remission” as Partial Mayo Score <2 without steroid use, and “clinical response” as reduction of the Partial Mayo Score ≥2 points compared with baseline, with a concomitant decrease of steroid dosage until its discontinuation within 8 weeks. Both outcomes were considered as “clinical benefit”. Patient data were weighted with the IPTW (Inverse Probability of Treatment Weighting). Results: The study included 197 patients: 118 treated with ADA and 79 with GOL, with a median follow up of 40.21 weeks for ADA and 34.00 weeks for GOL (p=0.075). 88 patients were naïve to anti-TNFα, 59 treated with ADA and 29 with GOL (p=0.090). After 8 weeks, clinical benefit was achieved in 93/118 (78.8%) patients treated with ADA and in 50/79 (63.3%) patients treated with GOL (p=0.026); steroid-free remission was reported in 48/118 (40.7%) patients in the ADA group and in 20/79 (25.3%) patients in the GOL group (p=0.038). At the end of follow up, clinical benefit was achieved in 79/118 (66.9%) patients treated with ADA and in 37/79 (46.8%) patients treated with GOL (p=0.008); steroid-free remission was reported in 50/118 (42.4%) patients treated with ADA and in 23/79 (29.1%) patients treated with GOL (p=0.082). Propensity score weighting analysis confirmed these results. In ADA subgroup, patients with disease duration >5 years showed higher clinical benefit at 8 weeks and at the end of follow up; patients previously treated with two biologics showed lower rates of clinical benefit only at 8 weeks. In GOL subgroup, C-reactive protein value at baseline was associated with higher risk of drug discontinuation at the end of follow up; while extra-intestinal manifestations were associated with better outcome. Conclusions: This multicentre real life study shows that ADA and GOL are effective in induction and maintenance of clinical benefit in moderate to severe UC and that ADA seems to be more effective than GOL.