Benjamin Hsu

Janssen Research & Development, LLC, Raritan, New Jersey, United States

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Publications (39)290.21 Total impact

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    ABSTRACT: Background Serum biomarkers that can predict subsequent clinical or imaging outcomes would aid decision-making in the management of ankylosing spondylitis (AS). Objectives Using data from the golimumab (GLM) study, GO-RAISE, in patients with active AS, we analysed correlations between multiple serum biomarkers and inflammation as detected by magnetic resonance imaging (MRI) and AS Disease Activity Score (ASDAS). Methods In GO-RAISE, patients with moderately to severely active AS were randomized to SC GLM 50mg, 100mg, or PBO q4wks. PBO-treated patients crossed over to receive GLM at wk16 or 24. Spinal MRIs in the sagittal plane were acquired using 1.5T scanners with T1 and short tau inversion recovery (STIR) sequences at BL and wk14. 98 patients were scored for activity (ASspiMRI-a) and structural (ASspiMRI-c) scores. Radiographs and MRIs were assessed by 2 readers who were blinded to treatment and image time order. Mean scores were used for analyses. Sera were collected from 140 patients at baseline and wk14 for analysis of markers by ELISA and/or using a multiplex platform (Rules Based Medicine). Spearman correlation analyses with Bonferoni p-value adjustment and logistic regression were conducted to assess the relationship between 76 serum biomarker levels and ASDAS using C-reactive protein (ASDAS), ASspiMRI-a, or MRI-c score at various time points. Results Baseline ASDAS showed significant correlations with serum biomarkers for inflammation (IL-6, ICAM-1, haptoglobin, amyloid P) and lipid metabolism (Complement C3). BL IL-6 or TIMP-1 correlated with the reduction of ASspiMRI-a at wk14 in GLM-treated patients. Wk4 change in IL-6 and C3 also showed correlation with change in ASspiMRI-a at wk14. Development of new fatty degeneration in the spine at wk14 correlated with BL biomarkers involved in lipid metabolism (leptin, C3) and tissue remodeling (TIMP-1). Previously described predictors such as insulin, MMP-3, VEGF, or bone resorption markers did not have significant correlations with clinical or imaging outcomes. Conclusions This analysis suggests that serum biomarkers IL-6, TIMP-1, and C3 may be linked to a reduction in spinal inflammation in AS patients following GLM treatment. In addition, ICAM-1, haptoglobin and amyloid P correlate with baseline disease activity and may implicate novel roles for these factors in AS-related inflammation. Disclosure of Interest R. Inman Grant/research support from: Janssen R&D, LLC., X. Baraliakos Grant/research support from: Janssen R&D, LLC., K.-G. Hermann Grant/research support from: Janssen R&D, LLC., J. Braun Grant/research support from: Janssen R&D, LLC., A. Deodhar Grant/research support from: Janssen R&D, LLC., D. van der Heijde Grant/research support from: Janssen R&D, LLC., S. Xu Employee of: Janssen R&D, LLC., B. Hsu Employee of: Janssen R&D, LLC.
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) levels, although having been shown to predict radiographic progression, are known to decrease in patients (pts) with ankylosing spondylitis (AS) receiving tumor necrosis factor (TNF)-antagonists. Objectives Using data from the study GO-RAISE that demonstrated efficacy of golimumab (GLM) in pts with active AS, we analyzed correlations between serum VEGF and CRP levels, radiographic progression and inflammation as detected by magnetic resonance imaging (MRI). Methods In GO-RAISE, pts with definite AS, BASDAI ≥4, and back pain score ≥4 were randomized to SC GLM 50mg, 100mg, or PBO q4wks. PBO-treated pts crossed over to receive GLM at wk16/24. All pts had lateral view radiographs of the cervical and lumbar spine performed at baseline (BL), wk104, and wk208, all scored using the modified Stoke AS Spine Score (mSASSS). Spinal MRIs in the sagittal plane were acquired using 1.5T scanners with T1 and short tau inversion recovery (STIR) sequences at BL, wk14, and wk104 for 98 pts; images were scored using the AS spinal MRI score for activity (ASspiMRI-a) score. Radiographs and MRIs were assessed by two readers who were blinded to treatment and image time order, the mean scores were used for analysis. Sera were collected from 140 pts for analysis of CRP and VEGF at BL and multiple visits. Spearman correlation analyses were conducted to assess the relationship between VEGF or CRP levels and both mSASSS and MRI-a score at various time points through wk 208. In addition, logistic regression analyses were conducted to assess if VEGF levels conferred an increased risk of a change in mSASSS ≥2 or of syndesmophyte formation from baseline to wk104 or wk208. Syndesmophyte formation was defined as a change from a mSASSS score <2 at baseline to a score of ≥2 (syndesmophyte, bridging syndesmophyte) at wk104 or 208 identified in ≥1 vertebral corner by both readers. Results CRP serum levels correlated with mSASSS scores at baseline, but not with radiographic progression or changes in MRI-a scores over time. No significant correlations were observed between VEGF serum levels and mSASSS at any time point (Table). Logistic regression analyses failed to show an increased risk of changes in mSASSS >2 or of syndesmophyte formation at wk104 and wk208 associated with VEGF (odds ratio, range: 0.990-1.006, all p=n.s). While a good correlation was observed between changes in ASspiMRI-a and VEGF level at wk14 (p=0.0008), the analysis showed that baseline and wk14 VEGF levels were not predictive of MRI-a scores including change scores at wk104 (Table). Conclusions Confirming earlier data, CRP serum levels correlated with baseline mSASSS scores. However, they did not predict radiographic progression or spinal inflammation after anti-TNF treatment. When comparing this data with previous studies with historical cohorts, it needs to be taken into account that these and our pt population clearly differed. Similarly, both VEGF and CRP serum levels at baseline were not predictive of either radiographic progression or spinal inflammation in these anti-TNF treated patients. Overall, our data suggest that suppression of VEGF and CRP is not sufficient to halt new bone formation in AS. Disclosure of Interest X. Baraliakos Grant/research support: Janssen R & D, LLC, K.-G. Hermann Grant/research support: Janssen R & D, LLC, S. Xu Employee of: Janssen R & D, LLC, B. Hsu Employee of: Janssen R & D, LLC, J. Braun Grant/research support: Janssen R & D, LLC DOI 10.1136/annrheumdis-2014-eular.3735
    No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Magnetic resonance imaging (MRI) is a key tool for the assessment of inflammatory lesions used for diagnosis and the monitoring of treatment effects in patients (pts) with ankylosing spondylitis (AS). Objectives Using data from the anti-tumor-necrosis-factor (TNF) agent golimumab (GLM) in AS study (GO-RAISE), we analysed the distribution and course of inflammatory spinal lesions in different parts of the axial skeleton in detail before and after treatment with GLM in pts with active AS. Methods Complete MR images at baseline, 3 months (week 14 of the placebo [PBO]-controlled phase) and 2 years (end of open-label extension) of the study were available from 98 AS patients. Among all pts with inflammatory MRI activity at baseline (BL), the number (nr.) of spinal lesions at different time points was assessed. Both, general (total nr. of inflammatory lesions in the entire spine) and detailed (nr. of inflammatory lesions in the cervical [CS], thoracic [TS] and lumbar [LS] spine, in single vertebral units [VUs], in the upper and lower edges for anterior and posterior site of each vertebra, and in the zygoapophyseal joints [ZAJ] were assessed. Improvement in inflammation was defined as any decrease in the MRI score from baseline to year 2 of the study. Results Overall, evaluable inflamed VU and ZAJ lesions were seen in 81.6% and 31.6% of pts, respectively, while 22.4% of VUs/ZAJs had inf at BL. In patients showing inflammatory activity, the mean number of lesions/patient was 6.7 for VUs and 3.6 for ZAJs, with no difference between pts randomized to GLM or PBO. Inflammation present in ZAJ without concomitant VU inflammation was present in 43/4426 (0.97%) of all VUs, and this combination occurred in 19/91 (20.88%) patients. In detail, 7.2% of VU+ZAJ lesions were found in the CS, 27.9% in the TS and 27.9% in the LS. VU inflammation was detected more frequently in the anterior (23.5%) than in the posterior (8.5%) part of the LS. This difference was not observed in the CS and TS. The most frequently inflamed region in the CS was C7/T1, in the TS it was T8/9-T11/12 and in the LS, there was a fairly evenly distribution across VUs. After 3 months of GLM treatment, the percentage of VUs/ZAJs with inflammation decreased by 2.7%/0.7% in the CS, 17.3%/3.6% in the TS and 17.6%/2.7% in the LS, while almost no change was observed in the PBO pts. The decreased VU/ZAJ involvement afforded by GLM treatment was sustained through 2 years. Similarly, after up to 2 years of GLM treatment, the mean number of lesions/pt showing inflammatory activity decreased to 2.7 for VUs and 2.0 for ZAJs. Conclusions This analysis confirms the predominance of inflammatory spinal lesions at the lower TS and the LS. While ZAJ inflammation was evident in a substantial nr. of patients it was uncommon for it to occur in isolation in a non-inflamed VU. Inflammatory lesions of VUs and ZAJs are supplementary information to MRI scoring systems and may contribute to a better understanding of clinical trial data. The already reported significance of the lower TS in the inflammatory process in AS clearly needs further study. Disclosure of Interest X. Baraliakos Grant/research support: Janssen R & D, LLC, K.-G. Hermann Grant/research support: Janssen R & D, LLC, S. Xu Employee of: Janssen R & D, LLC, B. Hsu Employee of: Janssen R & D, LLC, J. Braun Grant/research support: Janssen R & D, LLC DOI 10.1136/annrheumdis-2014-eular.5745
    No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Spinal mobility, as assessed by the Bath Ankylosing Spondylitis Metrology Index, BASMI, and imaging findings have been reported to correlate on the group level. Treatment with anti-TNF leads to improvement of both spinal inflammation as assessed by magnetic resonance imaging (MRI) and total BASMI scores. Objectives Using data from the golimumab (GLM) in ankylosing spondylitis (AS) study (GO-RAISE), we analysed the relationship between single components of BASMI and MRI scores of the corresponding spinal segments in anti-TNF-treated AS patients. Methods Complete MR imaging sets and spinal mobility data were available for 91 pts who participated in GO-RAISE. The MRI scores for active (ASspiMRI-a) and chronic changes (ASspiMRI-c) of the cervical and lumbar spine were compared to BASMI values for the cervical (cervical rotation (CR) and tragus-to-wall (TTW)) and the lumbar (lumbar flexion (LF) and lateral lumbar flexion (LLF)) spine using the linear definition. Spearman correlation coefficients were calculated for baseline scores and for changes in both BASMI and ASspiMRI-a and -c measurements of patients treated with GLM or placebo (PBO) after 14 weeks and after 2 years of GLM therapy. Subanalyses were performed with regard to age. Results At baseline, ASspiMRI-a scores of the cervical spine correlated with TTW (r=0.31, p=0.003) and CR (r=0.32, p=0.002) measurements, while ASspiMRI-a scores of the lumbar spine correlated with LF and LLF scores (both r=0.41, p<0.0001). In addition, ASspiMRI-c scores of the cervical spine correlated with TTW (r=0.46) and CR (r=0.45), both p<0.0001, while ASspiMRI-c scores of the lumbar spine correlated with LF (r=0.34, p=0.001) and LLF scores (r=0.41, p<0.0001). ASspiMRI-a scores correlated better in patients <40 years (TTW: r=0.31, p=0.04, LLF: r=0.42, p=0.005), while ASspiMRI-c scores correlated better in patients >40 years (TTW: r=0.35, p=0.015, LLF: r=0.48, p<0.001). In contrast, no significant correlations were found in change scores (data not shown). There was a negative correlation between MRI chronicity scores and lateral lumbar flexion at 2y: r=-0.26, p=0.037. Conclusions Our data confirm earlier reports on patients with active AS which showed that both inflammation and structural changes contribute to impairments of spinal mobility. In addition, we demonstrate significant correlations of MRI findings with detailed spinal mobility measures before anti-TNF treatment was started. Inflammatory changes had greater impact on spinal mobility in younger patients, while structural changes had more influence on spinal mobility in older patients. The correlation of the observed changes in MRI scores and spinal mobility was significant but not high. This may be due to the different mixture of active and chronic changes in individual patients. Disclosure of Interest X. Baraliakos Grant/research support: Janssen Research & Development, LLC, K.-G. Hermann Grant/research support: Janssen Research & Development, LLC, S. Xu Grant/research support: Janssen Research & Development, LLC, B. Hsu Grant/research support: Janssen Research & Development, LLC, J. Braun Grant/research support: Janssen Research & Development, LLC DOI 10.1136/annrheumdis-2014-eular.3781
    No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background The pathogenesis of new bone formation in ankylosing spondylitis (AS), is largely unknown. One emerging hypothesis implies that inflammation and fatty degeneration (Fat), play a role in syndesmophyte formation. Objectives Using data from the golimumab (GLM) AS study (GO-RAISE), we assessed how fatty and inflammatory lesions as detected by magnetic resonance imaging (MRI) related to new bone formation on x-rays. Methods In GO-RAISE, 98 of 356 patients with definite AS, BASDAI ≥4, who had been randomized to SC GLM 50mg, 100mg, or PBO q4wks and who underwent conventional radiography of the cervical and lumbar spine at baseline (BL), wks104 and 208, also had serial spine MRI scans taken in the sagittal plane using 1.5T scanners with T1 and short tau inversion recovery (STIR) sequences at BL, wk14, and wk104 in specialized centers. MRI reads were performed by two readers blinded to treatment and time order of the images, who evaluated vertebral corners on x-rays for syndesmophytes/bridging and on MRIs for active inflammation (Infl) and Fat on the level of predefined vertebral units (VU), including notation of the location by VU quadrant (upper, lower, anterior, posterior). The present analysis focused on the percentage of VU quadrants (VUq) with new syndesmophytes/bridging visible on x-ray, and on how this percentage varied by presence or absence of prior Infl or Fat in the corresponding VUq at BL and wk14. Results There were 91 patients in the substudy representing 4,368 VUq with evaluable images. Using only concordant scores of both readers, the percentage of VUq with new syndesmophytes at wk 104 or 208 was greater if Fat at BL and persisted wk14. New syndesmophytes were significantly more likely to develop in VUq with Fat present at both, BL and wk14, in comparison to those that did not have persistent fat (odds ratios for wk208 syndesmophyte/bridging Reader 1:, 3.27; Reader 2: 2.42). The combined presence of Fat and Infl lesions in a VUq at BL further increased the chance of new syndesmophytes which developed at the corresponding VUq (6.6% and 2.6% of corners with new syndesmophytes at wk104 for VU with BL Fat+Infl/wk14 Fat vs. BL Fat-no Infl/wk14 Fat, respectively. Conversely, for VUq without Fat or Infl at BL but wk14 Fat present, only 0-1.5% of VUq developed new syndesmophytes later. Conclusions This detailed analysis of radiographs and MRI at the vertebral level of the spine supports the hypothesis that in the spine of pts with AS, fatty degeneration and active inflammation favor progression towards subsequent growth of syndesmophytes and ankylosis. Disclosure of Interest X. Baraliakos Grant/research support: Janssen R & D, LLC, K.-G. Hermann Grant/research support: Janssen R & D, LLC, S. Xu Employee of: Janssen R & D, LLC, B. Hsu Employee of: Janssen R & D, LLC, J. Braun Grant/research support: Janssen R & D, LLC DOI 10.1136/annrheumdis-2014-eular.3009
    No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: To evaluate the effects of golimumab therapy on achieving inactive disease or major improvement, as assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS), and improvements in health-related quality of life (HRQOL) and productivity through 2 years in patients with AS. In the phase III GO-RAISE trial, 356 patients were randomized to placebo with crossover to golimumab 50 mg at Week 24 (n = 78), golimumab 50 mg (n = 138), or golimumab 100 mg (n = 140) at baseline and every 4 weeks. The proportions of patients with ASDAS major improvement (improvement ≥ 2.0) or inactive disease (score < 1.3) were determined. HRQOL was assessed using the 36-item Medical Outcomes Study Short Form-36 physical/mental component summary (SF-36 PCS/MCS) scores (normal score ≥ 50). The effect of disease on productivity was assessed by visual analog scale (0-10). Regression analyses on the association of disease activity and HRQOL were performed. The final assessment was at Week 104. Significantly greater proportions of golimumab-treated patients achieved ASDAS major improvement or inactive disease at weeks 14 and 24 versus placebo. Through Week 104, patients who achieved ASDAS inactive disease or major improvement had significantly greater improvements in SF-36 PCS and MCS scores and productivity than did patients not meeting these targets. Among all patients, achieving ASDAS inactive disease at weeks 52 and 104 was associated with normalized SF-36 PCS/MCS scores and significant improvements in work productivity. Greater proportions of golimumab-treated patients achieved ASDAS major improvement or inactive disease and improved HRQOL versus placebo. Achieving an inactive disease state by ASDAS criteria (< 1.3) was associated with normalized HRQOL through 2 years.
    No preview · Article · Apr 2014 · The Journal of Rheumatology
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    ABSTRACT: The safety and efficacy of sirukumab, an anti-interleukin-6 (IL-6) monoclonal antibody, were evaluated in a 2-part, placebo-controlled phase II study of patients with active rheumatoid arthritis (RA) despite methotrexate therapy. In Part A (proof-of-concept), 36 patients were randomised to placebo or sirukumab 100 mg every 2 weeks (q2w) through week 10, with crossover treatment during weeks 12-22. In Part B (dose finding), 151 patients were randomised to sirukumab (100 mg q2w, 100 mg q4w, 50 mg q4w, or 25 mg q4w) through week 24, or placebo through week 10 with crossover to sirukumab 100 mg q2w (weeks 12-24). The proportion of patients with an American College of Rheumatology 50 (ACR50) response and the change from baseline in the 28-joint count disease activity score using C-reactive protein (DAS28-CRP) were determined. Safety was evaluated through week 38 in both parts. The primary endpoint (ACR50 at week 12 in Part B) was achieved only with sirukumab 100 mg q2w versus placebo (26.7% vs 3.3%; p=0.026). Greater improvements in mean DAS28-CRP at week 12 were observed with sirukumab 100 mg q2w versus placebo in Parts A (2.1 vs 0.6, p<0.001) and B (2.2 vs 1.1; p<0.001). The incidence of adverse events (AEs) was similar for sirukumab-treated and placebo-treated patients through week 12 in Part A (70.6% and 63.2%, respectively) and B (67.8% and 66.7%, respectively). Infections were the most common type of AE; one death occurred (Part B, sirukumab 100 mg q2w, brain aneurysm). Sirukumab-treated patients experienced improvements in the signs/symptoms of RA. Safety results through 38 weeks were consistent with other IL-6 inhibitors. NCT00718718.
    Preview · Article · Apr 2014 · Annals of the rheumatic diseases
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    ABSTRACT: Objectives To present analysis of pooled data through approx 3yrs of follow-up from 5 ongoing golimumab (GLM) Ph3 SC trials across rheumatological indications and through 1yr in a completed Ph2 RA trial. Methods SC placebo (PBO) or GLM (50mg or100mg) was administered q4wks in Ph3 and q2/4wks in Ph2 trials. After wk24/52, pts in the Ph3 studies entered LTE and received GLM50mg or 100mg q4wks in an unblinded fashion. Dose escalation from 50mg to 100mg was allowed; no dose reduction permitted. Concomitant meds included DMARDs (mostlyMTX). AE were analyzed based on treatment received prior to occurrence of AE. Because pts could cross-over from PBO to GLM or increase GLM dose from 50mg to 100mg in cases of inadequate response in the Ph3 trials, a pt may appear in more than one column. Due to the short duration of the PBO-controlled portion, comparisons between (btwn) the GLM and PBO grps are limited. Results In combined Ph2/3 trials, 674pts received PBO, 1317 GLM50mg, and 1571 GLM100mg through 3yrs. In Ph3, 4.9%, 7.4%, and 10.5% of PBO, GLM50, GLM100mg pts, respectively, DC’d due to AE through 3yrs. In Ph2, 5.9% of PBO and 8.0% of GLM pts DC’d due to AE through 1yr. The incidences per 100PY of deaths, serious infections (including TB,opportunistic infections [OI]), demyelination, and malignancies are presented. Injection site reactions were low; most were mild, and 2 cases led to DC. No GLM SC-treated pt developed anaphylaxis/serum sickness-like reaction. Malignancies occurring during the 5 Ph3 and 1 Ph2 included skin cancers, solid tumors, and lymphoma. In comparison to SEER, overall incidence of malignancies in GLM-and PBO-treated pts was similar to that expected in the general US population. Incidence of lymphomas per 100 pt-years of follow-up was greater in the GLM100mg dose grp through 3yrs and higher than that expected in the general US population. Conclusions The safety of continued SC GLM exposure,demonstrates that GLM was generally well-tolerated with overall low rates of DC due to AEs. Safety profiles were generally similar btwn GLM dose with exception of higher rates of serious infections, including TB and OI, and lymphoma in the GLM100mg grp. Results are confounded by LTE design in which pts could receive GLM100mg after being exposed to GLM50mg with higher GLM dose used for pts with more active disease, and by limited exposure to PBO making the comparisons btwn PBO and treatment grps of less value. Disclosure of Interest J. Kay Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study, R. Fleischmann Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study, E. Keystone Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study, E. Hsia Employee of: Janssen Research & Development, LLC, M. Doyle Employee of: Janssen Research & Development, LLC, B. Hsu Employee of: Janssen Research & Development, LLC, M. Mack Employee of: Janssen Research & Development, LLC, A. Beutler Employee of: Janssen Research & Development, LLC, J. Braun Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study, A. Kavanaugh Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study
    Full-text · Article · Jan 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Objectives To summarize changes from baseline in HRQOL, impact of disease on work productivity, employability, and healthcare resource utilization among patients with rheumatoid arthritis(RA), psoriatic arthritis(PsA), and ankylosing spondylitis(AS) treated with golimumab(GLM) through 5yrs. Methods Patients with active RA despite MTX (GO-FORWARD), active PsA (GO-REVEAL), and active AS (GO-RAISE) were randomized to placebo (PBO) or GLM (50mg or 100mg Q4w). In GO-FORWARD, treatment also included concomitant MTX (GLM monotherapy in GO-FORWARD was not included in this analysis). Patients randomized to PBO crossed over to GLM at wk 24, with follow-up through wk256. HRQOL was measured using 36-item short -form of health survey (SF-36); impact of disease on work productivity was measured using a VAS scale (0=no impact, 10=impact very much); Employable was defined as being actively employed or to be able to work if a job was available. Healthcare resource utilization included the number of physician visits in the past 4 wks, ER visit in the past 3 months, and hospitalizations in the past 12 months. Changes from baseline through wk 256 in SF-36 PCS and MCS, work productivity, employability, and healthcare resource utilization were summarized from observed patients. Results At baseline, both mean SF-36 PCS (30.19, 32.91, and 30.00) and MCS (43.65, 45.19, and 44.03) scores in the combined GLM group for RA, PsA, and AS, respectively were below the US norm, indicating impaired HRQOL. Baseline percent of RA, PsA, and AS patients unemployable before retirement were 13.7%, 12.1%, and 14.1%, respectively. At wk24, RA, PsA, and AS GLM-treated pts had statistically significant greater improvement in both mean SF-36 PCS (7.65, 7.83, and 9.36, p<0.001) and MCS (3.07, 3.84, and 4.01, p <0.05) and had a statistically significant greater mean change from baseline in reduction in impact of disease on work productivity in the combined GLM-treated patients vs PBO (−1.987, −2.242, −2.805, all p<0.001) in RA, PsA and AS, respectively. At wk256, sustained improvement in SF-36 PCS and MCS was observed in the RA, PsA, and AS GLM-treated patients (mean change from baseline: PCS 9.3, 9.8, and 13.0 and MCS 4.5, 4.7, and 5.1, respectively), while mean change in impact of disease on work productivity for RA, PsA, and AS was −2.71, −3.0, and, −3.9, respectively. In addition, RA, PsA, and AS patients employable at baseline remained employable (all >95%), while those unemployable at baseline became more likely to be employable (RA 33.3%, PsA 64.3%, and AS 76.5%) at Wk256. A reduction in physician visits (RA −84%, PsA −89%, and AS −88%) was observed, as well as a reduction in the number of hospitalizations, ER visits, and days hospitalized, although these events were rare. Patients randomized to PBO at baseline and crossed-over to active treatment achieved similar outcomes overtime as those patients who were randomized to active treatment at baseline. Conclusions GLM-treated patients showed sustained improvement in HR QoL, reduced impact of disease on work productivity, improved employability, and less healthcare resource utilization through 5yrs. Disclosure of Interest None Declared
    No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Significantly greater improvements in health-related quality of life (HRQoL) and reduction of impact of disease on work productivity were observed in patients (pts) with ankylosing spondylitis (AS) treated with golimumab when compared with placebo at weeks 14 and 24. Objectives This analysis examined association of ASDAS major improvement and inactive disease with these improvements and the maintenance over two years. Methods In the GO-RAISE study, 356 pts with definite AS according to the modified NY criteria were randomly assigned in a 1.8:1.8:1 ratio to receive subcutaneous injections of golimumab 50 or 100 mg or placebo every 4 weeks. HRQoL was assessed using the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the SF-36. Self-reported employability data, defined as currently working or able to work if a job is available, were collected. Impact of disease on productivity in daily work, school or home was assessed using a visual analogue scale (0-10), with higher values indicating greater impact. ASDAS (based on CRP) inactive disease was defined as a score of <1.3 and major improvement was defined as an improvement from baseline ≥2. An ANOVA on van der Waerden normal scores was used for numeric comparisons and chi-square tests for dichotomous comparisons. Results At weeks 14 and 24 the combined golimumab groups had greater median improvements in ASDAS scores compared with placebo (1.6 vs. 0.4 and 1.7 vs. 0.3, respectively, p<0.001 for both). At weeks 52 and 104, when all pts received golimumab, all groups had comparable improvements in ASDAS, ranging from 1.9 to 2.3. For all pts, 33.9% and 41.6% achieved ASDAS inactive disease at week 52 and 104. Pts with major improvement for these time points were 49.1% and 52.9%. For pts achieving ASDAS inactive disease at weeks 52 and 104, 57.1% and 65.5%, respectively, had PCS ≥50. Inactive disease pts had 64.8% and 74.14% with MCS ≥50. Pts with ASDAS major improvement had 37.9% and 48.3% with PCS ≥50 and 62.1% and 65.31% with MCS ≥50 for these time points. Improvements in productivity were greater for pts with ASDAS inactive disease compared with non-inactive disease at weeks 52 and 104 (5.8 vs. 2.9 and 5.8 vs. 3.1, p<0.001 for both). Similar results were achieved for ASDAS responders compared with non-responders (5.4 vs. 2.4 and 5.8 vs. 2.6, p<0.001 for both). At baseline 40 pts were unemployable because of AS. At week 52, 6 of the 16 (37.5%) pts who achieved inactive disease regained employability, while 11 of the 16 (73.3%) pts who had major improvement regained employability. At week 104, 7 of the 18 (38.9%) pts who achieved inactive disease regained employability, while 13 of the 18 (72.2%) pts who had major improvement regained employability. Conclusions Achieving ASDAS inactive disease or major improvement in pts with AS after treatment with golimumab is associated with improvements in HRQoL and productivity. A trend towards regaining employability was observed for pts with clinical improvements, but this association would need to be substantiated in larger studies. Disclosure of Interest D. van der Heijde Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study, A. Deodhar Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study, J. Braun Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study, M. Mack Employee of: Janssen Research & Development, LLC, B. Hsu Employee of: Janssen Research & Development, LLC, T. Gathany Employee of: Janssen Global Service, LLC, C. Han Employee of: Janssen Global Service, LLC, R. Inman Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study
    No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Sirukumab (formerly named CNTO136) is a human mAb that binds with high affinity to the cytokine IL-6. In the proof of concept part (Part A) of this multicenter, randomized, double blind, PBO controlled, phase 2 study, 100mg sirukumab SC injections q2w were generally well tolerated and efficacious Objectives The phase 2 dose-ranging Part B was initiated after Part A to determine efficacious and safe sirukumab dose regimens. Methods In Part B, pts with active RA despite MTX were randomized equally to: (1) PBO q2wk at wks 0–10, then sirukumab 100 mg q2wk at wks12–24; (2) sirukumab 100 mg q2wk at wks 0–24; (3) sirukumab 100 mg q4wk at wks 0–24; (4) sirukumab 50 mg q4wk at wks 0–24; or (5) sirukumab 25 mg q4wk at wks 0–24. As reported previously, the primary endpoint (ACR50 response at wk 12) was achieved by the 100 mg q2wk and 50 mg q4wk doses. We now report specific changes observed through wk12 in the Health Assessment Questionnaire disability index (HAQ-DI), the physical component summary (PCS) score of the Short Form-36 (SF-36) scales, and individual ACR core components other than HAQ-DI. Two improvement thresholds (≥0.25 and ≥0.30) were used to define HAQ-DI response. Clinical response was assessed using the Disease Activity Score (employing 28 joints and C-reactive protein, DAS28-CRP) and Clinical Disease Activity Index (CDAI). The study was only powered for the primary endpoint. An intent-to-treat analysis of pts according to original treatment assignments was conducted, with imputation of missing data by carrying forward the last observation and treatment failure rules for non-responders. Results In Part B, 151 pts were randomized and treated. At baseline, mean age: 53±11 yrs, mean weight: 69±15 kg, mean DAS28 (CRP): 5.9±0.9, and median serum CRP: 1.7 mg/dL. Mean baseline HAQ-DI scores (1.54±0.64) were comparable between treatment groups; mean SF-36 PCS score (31.55±7.78) was notably below the general population norm. At wk12, a higher proportion of pts achieved HAQ-DI response, significantly greater improvement in HAQ-DI was observed in the combined sirukumab group (mean±sd: 0.42±0.53) compared to PBO (0.15±0.56) (p=0.012). No apparent sirukumab dose response was observed. HAQ-DI response was observed as early as wk2 and increased over time through wk24 in all 5 treatment groups. At wk12, greater improvement in SF-36 PCS score was observed in the combined sirukumab group compared with PBO (p=0.038). Also, statistically significant improvement in the combined sirukumab group vs. PBO was observed for each of the ACR core components, except for tender joint count, which trended toward improvement (p=0.06). Pain (p=0.010), physician global (p=0.005), and CRP (p<0.001) appeared to show the greatest short-term response to sirukumab treatment. Significant clinical improvement in the combined sirukumab group vs. PBO was evident at wk12 when assessed either by change from baseline in DAS28 (CRP) (p<0.001) or by change in the CDAI score (p=0.009). Conclusions In this Phase 2 study of patients with active RA despite MTX therapy, sirukumab in combination with MTX, improved physical function as well as reduced multiple other signs and symptoms of RA. Disclosure of Interest B. Hsu: None Declared, C.-F. Chiou: None Declared, S. Sheng Employee of: Janssen Research & Development, LLC, J. Smolen Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study, M. Weinblatt Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study
    No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Golimumab(GLM) has demonstrated significant and sustained clinical efficacy and an acceptable safety profile through 2yrs of the phase 3, randomized, PBO-controlled, GO-RAISE study in pts with ankylosing spondylitis (AS). Objectives To evaluate GLM safety/efficacy in AS pts receiving GLM50mg and/or 100mg through 5yrs. Methods 356pts with AS were randomized to SC PBO, GLM50mg, or GLM100mg q4w. At wk16, pts with inadequate response early escaped (EE) with blinded dose adjustments (PBO→GLM50mg, GLM50mg→ 100mg). At wk24, pts still receiving PBO crossed over to GLM50mg. Pts continued double-blind treatment through wk100. The long-term extension started with the wk104 GLM injection. Pts received GLM q4w for ~5yrs (final injection at wk252). After unblinding at wk104 and at the investigator’s discretion, pts receiving GLM50mg could increase their dose to 100mg; pts receiving GLM100mg could decrease dose to 50mg; concomitant DMARD, corticosteroid, and NSAID therapy could be adjusted. Results Among 356 randomized pts, 254 pts continued treatment through wk252; 242 completed the safety follow-up through wk268. 101 pts withdrew (33 [9.3%] due to AEs, 35 [9.8%] lack of efficacy, 11 [3.1%] lost to follow-up, 22 [6.2%] for other reasons); 1pt was untreated. Reductions in AS-related signs/symptoms and improvements in physical function and range of motion observed at wk14 (primary endpoint visit; previously reported) were maintained through 5yrs (Table). Serious AEs were reported for 17.1% of GLM50mg, 24.7% of GLM100mg, and 22.0% of all GLM-treated pts. One pt died (GLM50mg, B cell lymphoma after 3yrs in the study, followed by pancreatic cancer). Conclusions In pts with active AS, SC GLM50 and 100mg q4w improved AS signs/symptoms, physical function, and range of motion and demonstrated an acceptable safety profile that was consistent with previously reported results for GLM through wk160 and with other anti-TNF biologics. There were no differences between the two GLM dosages. Disclosure of Interest A. Deodhar Grant/research support from: Janssen R&D, LLC, J. Braun Grant/research support from: Janssen R&D, LLC, R. Inman Grant/research support from: Janssen R&D, LLC, D. van der Heijde Grant/research support from: Janssen R&D, LLC, Y. Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen R&D, LLC, B. Hsu Shareholder of: Johnson & Johnson, Employee of: Janssen R&D, LLC
    No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Background Three clinical trials in which structural spinal changes in patients with ankylosing spondylitis (AS) treated with tumor necrosis factor (TNF) antagonists over 2 years (yrs) were assessed in comparison to a historical cohort have indicated that such therapy may not alter radiographic progression as quantified by the modified Stokes Ankylosing Spondylitis Spinal Score (mSASSS). Longer-term data are scarce. Objectives The purpose of this study is to assess the effects of the anti-TNF agent golimumab (GLM) on radiographic progression in patients (pts) with AS through 2 and 4 yrs of treatment. Methods Pts (n=356) were randomly assigned (1:1.8:1.8) to subcutaneous injections of PBO, GLM 50mg, or GLM 100mg q4weeks (wks). At wk16, pts in the PBO or 50mg groups with <20% improvement in both total back pain and morning stiffness entered early escape (EE) to GLM 50 or 100mg, respectively. At wk24, pts still receiving PBO crossed over (CO) to GLM 50mg. Lateral view radiographs of the cervical and lumbar spine were performed at baseline, wk104 and wk208. Radiographs were read by 2 independent, central, trained readers using mSASSS methodology (0=normal; 1=erosion, sclerosis, or squaring; 2=syndesmophyte; 3=bridging syndesmophyte). The mSASSS ranges from 0-72. Results Among all randomized pts, median time since first AS symptoms was 11.0 yrs. Treatment groups were comparable with regard to age, gender, BASDAI, BASFI, BASMI, CRP, mSASSS, and baseline syndesmophytes. Overall mean changes in mSASSS were 1.1 at wk104, with no obvious treatment group differences, and 3.6 at wk208, with numerically larger changes in the GLM 100mg group (Table). Due to wide distribution of change values, the numerical differences in mean change in mSASSS for the 100mg group or for the 19 radiographically evaluable pts who dose-escalated from 50 to 100mg via EE (data not shown) are not significant by ANOVA on the van der Waerden normal scores. At wk 104 and wk 208, 23.1% and 35.1% of pts had a definitive change (>2 points) in mSASSS. Conclusions Changes in mSASSS from baseline to wk104 and wk208 indicated that anti-TNF treatment with GLM does not inhibit radiographic progression in the spine of pts with AS. Disclosure of Interest J. Braun Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study, D. van der Heijde Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study, K.-G. Hermann Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study, X. Baraliakos Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study, A. Deodhar Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study, A. Beutler Employee of: Janssen Research & Development, LLC, M. Mack Employee of: Janssen Research & Development, LLC, W. Xu Employee of: Janssen Research & Development, LLC, B. Hsu Employee of: Janssen Research & Development, LLC, R. Inman Grant/Research support from: Investigators for Janssen Research & Development, LLC sponsored clinical study
    No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: To assess pooled golimumab safety up to year 3 of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) trials. Golimumab 50 and 100 mg, administered subcutaneously (SC) every 4 weeks (q4wk), were assessed in patients with active RA (methotrexate-naïve, methotrexate-experienced and anti-TNF (tumour necrosis factor)-experienced), PsA or AS, despite conventional therapy. Placebo control continued up to week (wk) 24 (wk 52, methotrexate-naïve), with early escape at wk 16 (wk 28, methotrexate-naïve); subsequently, all patients received golimumab 50 or 100 mg q4wk. After the blinded controlled period, golimumab doses could be adjusted per investigator discretion. Pooled safety analyses reported herein include data from placebo-controlled and uncontrolled study periods up to wk 160. Determinations of incidences/100 patient-years (pt-yrs) for rare events also included RA patients from a phase IIb trial. Across five phase III trials of SC golimumab, 639 patients received placebo and 2226 received golimumab 50 mg (n=1249) and/or 100 mg (n=1501) up to wk 160 (patients may be included in more than one group because non-responders were allowed early escape); 1179 patients were treated for ≥156 weeks. For placebo, golimumab 50 mg and golimumab 100 mg, respective adverse event incidences/100 pt-yrs (95% CIs) up to wk 160 were: 0.28 (0.01 to 1.56), 0.30 (0.12 to 0.62), 0.41 (0.23 to 0.69) for death; 5.31 (3.20 to 8.30), 3.03 (2.36 to 3.82), 5.09 (4.36 to 5.90) for serious infection; 0.00 (0.00 to 0.84), 0.17 (0.05 to 0.44), 0.35 (0.18 to 0.62) for tuberculosis; 0.00 (0.00 to 0.84), 0.13 (0.03 to 0.38), 0.24 (0.10 to 0.46) for opportunistic infection; 0.00 (0.00 to 0.84), 0.00 (0.00 to 0.13), 0.12 (0.03 to 0.30) for demyelination; and 0.00 (0.00 to 0.84), 0.04 (0.00 to 0.24), 0.18 (0.06 to 0.38) for lymphoma. SC golimumab safety up to 3 years remained consistent with that of other TNF antagonists. Golimumab 100 mg showed numerically higher incidences of serious infections, demyelinating events and lymphoma than 50 mg; safety follow-up up to year 5 continues.
    Full-text · Article · Dec 2013 · Annals of the rheumatic diseases
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    ABSTRACT: Objective: To evaluate the effect of golimumab on haemoglobin levels in patients with RA, PsA or AS. Methods: Secondary analysis was performed on integrated data from five randomized controlled studies: three RA, one PsA and one AS (2303 patients total). Golimumab 50 or 100 mg was injected s.c. every 4 weeks with or without MTX. Control groups received placebo injections plus MTX or background therapy. Patients with haemoglobin levels below the age- and sex-specific normal ranges were considered to have anaemia. Ferritin levels were used to distinguish anaemia of mixed aetiology (≥ 15 and <60 ng/ml) and anaemia of inflammation (≥ 60 ng/ml). Changes from baseline to weeks 14 and 24 in haemoglobin level were compared between treatment groups using an analysis of variance on the van der Waerden normal scores. Results: At baseline, 21% of RA patients, 9% of PsA patients and 15% of AS patients had anaemia. Of these, 24%, 57% and 25%, respectively, had anaemia of inflammation. The median increase from baseline to week 14 in the haemoglobin level of anaemic patients was 0.3 g/dl in the control group and 0.9 g/dl in the golimumab group (P < 0.001). Haemoglobin levels improved within the subgroups of patients with anaemia of mixed aetiology (control, 0.4 g/dl vs golimumab, 0.7 g/dl) (P = 0.305) and with anaemia of inflammation (0.2 vs 1.4 g/dl, respectively) (P < 0.001). Conclusion: Compared with the control group, patients receiving golimumab treatment had significantly improved haemoglobin levels, particularly among patients with anaemia of inflammation.
    Full-text · Article · Jul 2013 · Rheumatology (Oxford, England)
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    ABSTRACT: Objectives To describe safety of IV GLM in RA from the Ph3 GLM IV program. AE rates of interest are indirectly compared to those observed in the GLM SC clinical program across rheumatologic indications. Methods 2 multicenter, randomized, double-blind, PBO-controlled studies were included in the integrated IV safety analysis. GO-LIVE evaluated IV PBO or GLM 2mg/kg or 4mg/kg, ± MTX q12wks in pts with active RA despite MTX. GO-FURTHER is evaluating GLM 2mg/kg IV at wks 0,4, and q8wks +MTX in active RA despite MTX. In the SC GLM program (GO-FORWARD, GO-BEFORE, GO-AFTER [RA], GO-REVEAL [PsA], GO-RAISE [AS]), PBO or GLM (50mg/100mg) was administered SC q4wks in Ph3 and q2 or 4 wks in Ph2. Approx. half of pts received MTX. Safety findings for the Ph3 GLM IV RA studies combined through the IV dosing period of GO-LIVE (median 60wks exposure) and through the August 15,2012 cut-off for GO-FURTHER (median 92wks exposure) are reported; for the ongoing SC studies the data cut was through wk160. Comparison of targeted safety events between IV and SC GLM are reported. Pts who received ≥1administration were analyzed. Results 1210pts were treated with IV GLM in the integrated Ph3 RA IV studies with median duration of follow-up of 72.7wks. Overall AEs observed in the integrated Ph3 RA IV program are summarized (Table). Since follow-up was longer for the SC rheumatology program, more overall events were observed;however when corrected for events/100 pt yrs, no difference in AE rates or significant SAEs were observed between GLM IV and SC. Incidence of non-serious infusion reactions (median 30 min infusions) remained low regardless of infusion length, and no serious infusion reactions, requiring study d/c, were reported. NMSC(incidence/100 pt-yrs of f/u:0.49[95%CI:0.33,0.71] vs 0.14[95%CI:0.03,0.42] for GLM SC vs GLM IV) and lymphoma rates were numerically higher in the GLMSC grp vs the GLMIV grp. Conclusions Overall safety of IV GLM in RA pts observed through Aug 15,2012 continue to demonstrate an acceptable safety profile. Rates for events of interest such as malignancies and serious infections in the IV studies are comparable with or lower than rates in the SC studies in RA pts, AS, and PsA. Follow-up through 2yrs will provide information regarding long-term safety of IV GLM. Disclosure of Interest R. Westhovens Grant/research support from: Janssen R&D, LLC, C. Bingham III Grant/research support from: Janssen R&D, LLC, M. Weinblatt Grant/research support from: Janssen R&D, LLC, R. Fleischmann Grant/research support from: Janssen R&D, LLC, E. Keystone Grant/research support from: Janssen R&D, LLC, E. Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen R&D, LLC, B. Hsu Shareholder of: Johnson & Johnson, Employee of: Janssen R&D, LLC, L. Kim Shareholder of: Johnson & Johnson, Employee of: Janssen R&D, LLC, S. Mudivarthy Shareholder of: Johnson & Johnson, Employee of: Janssen R&D, LLC, M. Mack Shareholder of: Johnson & Johnson, Employee of: Janssen R&D, LLC, N. Goldstein Shareholder of: Johnson & Johnson, Employee of: Janssen R&D, LLC, J. Braun Grant/research support from: Janssen R&D, LLC, A. Kavanaugh Grant/research support from: Janssen R&D, LLC, A. Mendelsohn: None Declared, J. Kay: None Declared
    Full-text · Article · Jun 2013 · Annals of the Rheumatic Diseases
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    Full-text · Article · Jun 2013 · Annals of the rheumatic diseases
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    ABSTRACT: Objective To evaluate radiographic progression in patients with ankylosing spondylitis (AS) receiving two different doses of the tumour necrosis factor antagonist golimumab. Methods 356 patients with AS were randomly assigned to placebo, or golimumab 50 mg or 100 mg every 4 weeks (wks). At wk16, patients with inadequate response early escaped with blinded dose adjustments (placebo→golimumab 50 mg, 50 mg→100 mg). At wk24, patients still receiving placebo crossed over to golimumab 50 mg. Lateral view radiographs of the cervical/lumbar spine were obtained at wk0, wk104 and wk208, and scored (two blinded readers, modified Stoke AS Spine Score (mSASSS)). Observed data were used for wk104 analyses; missing wk208 scores were linearly extrapolated. Results Wk104 changes from baseline in mSASSS averaged 1.6±4.6 for placebo crossover, 0.9±2.7 for 50 mg and 0.9±3.9 for 100 mg. By wk208, following golimumab therapy for 3.5–4 years, mean changes in mSASSS were 2.1±5.2 for placebo crossover, 1.3±4.1 for 50 mg and 2.0±5.6 for 100 mg. Less than a third of patients (placebo crossover, 19/66 (28.8%); 50 mg, 29/111 (26.1%); 100 mg, 35/122 (28.7%)) had a definitive change from baseline mSASSS (>2). Less radiographic progression was observed through wk208 in patients without baseline syndesmophytes (0.2 vs 2.8 in patients with ≥1 syndesmophyte; p<0.0001) and with baseline C-reactive protein (CRP) levels ≤1.5 mg/dl (0.9 vs 2.9 with CRP >1.5 mg/dl; p=0.0004). Conclusions No difference in mSASSS change was observed between golimumab 50 mg and 100 mg. The radiographic progression rate remained stable at years 2 and 4, suggesting no acceleration of new bone formation over time. Golimumab-treated AS patients with no syndesmophytes and less systemic inflammation at baseline had considerably less radiographic progression.
    Preview · Article · May 2013 · Annals of the rheumatic diseases
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    ABSTRACT: 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.
    No preview · Article · Feb 2013
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    M. Genovese · A. Deodhar · E. Hsia · B. Hsu · Y.J. Lin · C. Han

    Preview · Article · Nov 2012 · Value in Health

Publication Stats

594 Citations
290.21 Total Impact Points

Institutions

  • 2011-2014
    • Janssen Research & Development, LLC
      Raritan, New Jersey, United States
  • 2013
    • Mayo Clinic - Rochester
      Рочестер, Minnesota, United States
  • 2010-2013
    • William Penn University
      Filadelfia, Pennsylvania, United States