Gobivaz

Pharmacotherapeutic group: Immunosuppressants, tumour necrosis factor alpha (TNF-α) inhibitors, ATC code: L04AB06. GOBIVAZ is a biosimilar medicinal product. Detailed information is available on the MHRA website https://www.gov.uk/government/organisations/medicines-and-healthcare- products-regulatory-agency. Mechanism of action Golimumab is a human monoclonal antibody that forms high affinity, stable complexes with both the soluble and transmembrane bioactive forms of human TNF-α, which prevents the binding of TNF-α to its receptors. Pharmacodynamic effects The binding of human TNF by golimumab was shown to neutralise TNF-α-induced cell-surface expression of the adhesion molecules E-selectin, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 by human endothelial cells. In vitro, TNF-induced secretion of interleukin (IL)-6, IL-8 and granulocyte-macrophage colony stimulating factor (GM-CSF) by human endothelial cells was also inhibited by golimumab. Improvement in C-reactive protein (CRP) levels were observed relative to placebo groups and treatment with golimumab resulted in significant reductions from baseline in serum levels of IL-6, ICAM-1, matrix-metalloproteinase (MMP)-3 and vascular endothelial growth factor (VEGF) compared to control treatment. In addition, levels of TNF-α were reduced in RA and AS patients and levels of IL-8 were reduced in PsA patients. These changes were observed at the first assessment (week 4) after the initial golimumab administration and were generally maintained through week 24. Clinical efficacy Rheumatoid arthritis The efficacy of golimumab was demonstrated in three multi-centre, randomised, double-blind, placebo-controlled studies in over 1500 patients ≥ 18 years of age with moderately to severely active RA diagnosed according to American College of Rheumatology (ACR) criteria for at least 3 months prior to screening. Patients had at least 4 swollen and 4 tender joints. Golimumab or placebo were subcutaneously administered every 4 weeks. GO-FORWARD evaluated 444 patients who had active RA despite a stable dose of at least 15 mg/week of MTX and who had not been previously treated with an anti-TNF agent. Patients were randomised to receive placebo + MTX, golimumab 50 mg + MTX, golimumab 100 mg + MTX or golimumab 100 mg + placebo. Patients receiving placebo + MTX were switched to golimumab 50 mg + MTX after week 24. At week 52, patients entered an open label long-term extension. GO-AFTER evaluated 445 patients who were previously treated with one or more of the anti-TNF agents adalimumab, etanercept, or infliximab. Patients were randomised to receive placebo, golimumab 50 mg, or golimumab 100 mg. Patients were allowed to continue concomitant DMARD therapy with MTX, sulfasalazine (SSZ), and/or hydroxychloroquine (HCQ) during the study. The stated reasons for discontinuation of prior anti TNF therapies were lack of efficacy (58%), intolerance (13%), and/or reasons other than safety or efficacy (29%, mostly for financial reasons). GO-BEFORE evaluated 637 patients with active RA who were MTX-naïve and had not previously been treated with an anti-TNF agent. Patients were randomised to receive placebo + MTX, golimumab 50 mg + MTX, golimumab 100 mg + MTX or golimumab 100 mg + placebo. At week 52, patients entered an open label long-term extension in which patients receiving placebo + MTX who had at least 1 tender or swollen joint were switched to golimumab 50 mg + MTX. In GO-FORWARD, the (co-)primary endpoints were the percentage of patients achieving an ACR 20 response at week 14 and the improvement from baseline in Health Assessment Questionnaire (HAQ) at week 24. In GO-AFTER, the primary endpoint was the percentage of patients achieving an ACR 20 response at week 14. In GO-BEFORE, the co-primary endpoints were the percentage of patients achieving ACR 50 response at week 24 and the change from baseline in the van der Heijde-modified Sharp (vdH-S) score at week 52. In addition to the primary endpoint(s), additional assessments of the impact of golimumab treatment on the signs and symptoms of arthritis, radiographic response, physical function and health-related quality of life were performed. In general, no clinically meaningful differences in measures of efficacy were observed between the golimumab 50 mg and 100 mg dosing regimens with concomitant MTX, through week 104 in GO-FORWARD and GO-BEFORE and through week 24 in GO-AFTER. In each of the RA studies by study design, patients in the long-term extension may have switched between the 50 mg and 100 mg golimumab doses at the discretion of the study physician. Signs and symptoms Key ACR results for the golimumab 50 mg dose at weeks 14, 24 and 52 for GO-FORWARD, GO-AFTER and GO-BEFORE are shown in Table 2 and are described below. Responses were observed at the first assessment (week 4) after the initial golimumab administration. In GO-FORWARD, among 89 subjects randomised to golimumab 50 mg + MTX, 48 were still on this treatment at week 104. Among those, 40, 33 and 24 patients had ACR 20/50/70 response, respectively at week 104. Among patients remaining in the study and treated with Golimumab, similar rates of ACR 20/50/70 response was observed from week 104 through week 256. In GO-AFTER, the percentage of patients achieving an ACR 20 response was greater for patients receiving golimumab than for patients receiving placebo regardless of the reason reported for discontinuation of one or more prior anti-TNF therapies. Table 2 Key efficacy outcomes from the controlled portions of GO-FORWARD, GO-AFTER and GO-BEFORE. GO-FORWARD Active RA despite MTX GO-AFTER Active RA, previously treated with one or more anti-TNF agent(s) GO-BEFORE Active RA, MTX Naïve Placebo + MTX Golimumab 50 mg + MTX Placebo Golimumab 50 mg Placebo + MTX Golimumab 50 mg + MTX n a 133 89 150 147 160 159 Responders, % of patients ACR 20 Week 14 33% 55%* 18% 35%* NA NA Week 24 28% 60%* 16% 31% p = 0.002 49% 62% Week 52 NA NA NA NA 52% 60% ACR 50 Week 14 10% 35%* 7% 15% p = 0.021 NA NA Week 24 14% 37%* 4% 16%* 29% 40% Week 52 NA NA NA NA 36% 42% ACR 70 Week 14 4% 14% p = 0.008 2% 10% p = 0.005 NA NA Week 24 5% 20%* 2% 9% p = 0.009 16% 24% Week 52 NA NA NA NA 22% 28% a n reflects randomised patients; actual number of patients evaluable for each endpoint may vary by timepoint. * p ≤ 0.001 NA: Not Applicable In GO-BEFORE the primary analysis in patients with moderate to severe rheumatoid arthritis (combined golimumab 50 and 100 mg + MTX groups vs MTX alone for ACR50) was not statistically significant at week 24 (p = 0.053). At week 52 in the overall population, the percentage of patients in the golimumab 50 mg + MTX group who achieved an ACR response was generally higher but not significantly different when compared with MTX alone (see Table 2). Additional analyses were performed in subsets representative of the indicated population of patients with severe, active and progressive RA. A generally greater effect of golimumab 50 mg + MTX versus MTX alone was demonstrated in the indicated population compared with the overall population. In GO-FORWARD and GO-AFTER, clinically meaningful and statistically significant responses in Disease Activity Scale (DAS)28 were observed at each prespecified time point, at week 14 and at week 24 (p ≤ 0.001). Among patients who remained on the golimumab treatment to which they were randomised at study start, DAS28 responses were maintained through week 104. Among patients remaining in the study and treated with golimumab, DAS28 responses were similar from week 104 through week 256. In GO-BEFORE, major clinical response, defined as the maintenance of an ACR 70 response over a continuous 6-month period, was measured. At week 52, 15% of patients in the golimumab 50 mg + MTX group achieved a major clinical response compared with 7% of patients in the placebo + MTX group (p = 0.018). Among 159 subjects randomised to golimumab 50 mg + MTX, 96 were still on this treatment at week 104. Among those, 85, 66 and 53 patients had ACR 20/50/70 response, respectively, at week 104. Among patients remaining in the study and treated with golimumab, similar rates of ACR 20/50/70 response were observed from week 104 through week 256. Radiographic response In GO-BEFORE the change from baseline in the vdH-S score, a composite score of structural damage that radiographically measures the number and size of joint erosions and the degree of joint space narrowing in hands/wrists and feet, was used to assess the degree of structural damage. Key results for the golimumab 50 mg dose at week 52 are presented in Table 3. The number of patients with no new erosions or a change from baseline in total vdH-S Score ≤ 0 was significantly higher in the golimumab treatment group than in the control group (p = 0.003). The radiographic effects observed at week 52 were maintained through week 104. Among patients remaining in the study and treated with golimumab, radiographic effects were similar from week 104 through week 256. Table 3 Radiographic mean (SD) changes from baseline in total vdH-S score at week 52 in the overall population of GO-BEFORE Placebo + MTX Golimumab 50 mg + MTX n a 160 159 Total Score Baseline 19.7 (35.4) 18.7 (32.4) Change from baseline 1.4 (4.6) 0.7 (5.2) * Erosion Score Baseline 11.3 (18.6) 10.8 (17.4) Change from baseline 0.7 (2.8) 0.5 (2.1) JSN Score Baseline 8.4 (17.8) 7.9 (16.1) Change from baseline 0.6 (2.3) 0.2 (2.0) ** a n reflects randomised patients * p = 0.015 ** p = 0.044 Physical function and health-related quality of life Physical function and disability were assessed as a separate endpoint in GO-FORWARD and GO-AFTER using the disability index of the HAQ DI. In these studies, golimumab demonstrated clinically meaningful and statistically significant improvement in HAQ DI from baseline versus control at week 24. Among patients who remained on the golimumab treatment to which they were randomised at study start, improvement in HAQ DI was maintained through week 104. Among patients remaining in the study and treated with golimumab, improvement in HAQ DI was similar from week 104 through week 256. In GO-FORWARD clinically meaningful and statistically significant improvements were demonstrated in health-related quality of life as measured by the physical component score of the SF-36 in patients treated with golimumab versus placebo at week 24. Among patients who remained on the golimumab treatment to which they were randomised at study start, improvement of the SF-36 physical component was maintained through week 104. Among patients remaining in the study and treated with golimumab, improvement of the SF-36 physical component was similar from week 104 through week 256. In GO-FORWARD and GO-AFTER, statistically significant improvements were observed in fatigue as measured by functional assessment of chronic illness therapy-fatigue scale (FACIT-F). Psoriatic arthritis The safety and efficacy of golimumab were evaluated in a multi-centre, randomised, double-blind, placebo-controlled study (GO-REVEAL) in 405 adult patients with active PsA (≥ 3 swollen joints and ≥ 3 tender joints) despite non-steroidal anti-inflammatory (NSAID) or DMARD therapy. Patients in this study had a diagnosis of PsA for at least 6 months and had at least mild psoriatic disease. Patients with each sub-type of psoriatic arthritis were enrolled, including polyarticular arthritis with no rheumatoid nodules (43%), asymmetric peripheral arthritis (30%), distal interphalangeal (DIP) joint arthritis (15%), spondylitis with peripheral arthritis (11%), and arthritis mutilans (1%). Previous treatment with an anti-TNF agent was not allowed. Golimumab or placebo were administered subcutaneously every 4 weeks. Patients were randomly assigned to placebo, golimumab 50 mg, or golimumab 100 mg. Patients receiving placebo were switched to golimumab 50 mg after week 24. Patients entered an open label long-term extension at week 52. Approximately forty-eight percent of patients continued on stable doses of methotrexate (≤ 25 mg/week). The co-primary endpoints were the percentage of patients achieving ACR 20 response at week 14 and change from baseline in total PsA modified vdH-S score at week 24. In general, no clinically meaningful differences in measures of efficacy were observed between the golimumab 50 mg and 100 mg dosing regimens through week 104. By study design, patients in the long-term extension may have switched between the 50 mg and 100 mg golimumab doses at the discretion of the study physician. Signs and symptoms Key results for the 50 mg dose at weeks 14 and 24 are shown in table 4 and described below. Table 4 Key efficacy outcomes from GO-REVEAL Placebo Golimumab 50 mg* n a 113 146 Responders, % of patients ACR 20 Week 14 9% 51% Week 24 12% 52% ACR 50 Week 14 2% 30% Week 24 4% 32% ACR 70 Week 14 1% 12% Week 24 1% 19% PASI b 75 c Week 14 3% 40% Week 24 1% 56% * p < 0.05 for all comparisons; a n reflects randomised patients; actual number of patients evaluable for each endpoint may vary by timepoint b Psoriasis Area and Severity Index c Based on the subset of patients with ≥ 3% BSA involvement at baseline, 79 patients (69.9%) in the placebo group and 109 (74.3%) in the golimumab 50 mg group. Responses were observed at the first assessment (week 4) after the initial golimumab administration. Similar ACR 20 responses at week 14 were observed in patients with polyarticular arthritis with no rheumatoid nodules and asymmetric peripheral arthritis PsA subtypes. The number of patients with other PsA subtypes was too small to allow meaningful assessment. Responses observed in the golimumab treated groups were similar in patients receiving and not receiving concomitant MTX. Among 146 patients randomised to golimumab 50 mg, 70 were still on this treatment at week 104. Of these 70 patients, 64, 46 and 31 patients had an ACR 20/50/70 response, respectively. Among patients remaining in the study and treated with golimumab, similar rates of ACR 20/50/70 response was observed from week 104 through week 256. Statistically significant responses in DAS28 were also observed at weeks 14 and 24 (p < 0.05). At week 24 improvements in parameters of peripheral activity characteristic of psoriatic arthritis (e.g. number of swollen joints, number of painful/tender joints, dactylitis and enthesitis) were seen in the golimumab-treated patients. Golimumab treatment resulted in significant improvement in physical function as assessed by HAQ DI, as well as significant improvements in health-related quality of life as measured by the physical and mental component summary scores of the SF-36. Among patients who remained on the golimumab treatment to which they were randomised at study start, DAS28 and HAQ DI responses were maintained through week 104. Among patients remaining in the study and treated with golimumab, DAS28 and HAQ DI responses were similar from week 104 through week 256. Radiographic response Structural damage in both hands and feet was assessed radiographically by the change from baseline in the vdH-S score, modified for PsA by addition of hand distal interphalangeal (DIP) joints. Golimumab 50 mg treatment reduced the rate of progression of peripheral joint damage compared with placebo treatment at week 24 as measured by change from baseline in total modified vdH-S Score (mean ± SD score was 0.27 ± 1.3 in the placebo group compared with -0.16 ± 1.3 in the golimumab group; p = 0.011). Out of 146 patients who were randomised to golimumab 50 mg, 52 week X-ray data were available for 126 patients, of whom 77% showed no progression compared to baseline. At week 104, X-ray data were available for 114 patients, and 77% showed no progression from baseline. Among patients remaining in the study and treated with golimumab, similar rates of patients showed no progression from baseline from week 104 through week 256. Axial spondyloarthritis Ankylosing spondylitis The safety and efficacy of golimumab were evaluated in a multi-centre, randomised, double-blind, placebo-controlled study (GO-RAISE) in 356 adult patients with active ankylosing spondylitis (defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 and a VAS for total back pain of ≥ 4, on a scale of 0 to 10 cm). Patients enrolled in this study had active disease despite current or previous NSAID or DMARD therapy and had not previously been treated with anti-TNF therapy. Golimumab or placebo were administered subcutaneously every 4 weeks. Patients were randomly assigned to placebo, golimumab 50 mg and golimumab 100 mg and were allowed to continue concomitant DMARD therapy (MTX, SSZ and/or HCQ). The primary endpoint was the percentage of patients achieving Ankylosing Spondylitis Assessment Study Group (ASAS) 20 response at week 14. Placebo-controlled efficacy data were collected and analysed through week 24. Key results for the 50 mg dose are shown in Table 5 and described below. In general, no clinically meaningful differences in measures of efficacy were observed between the golimumab 50 mg and 100 mg dosing regimens through week 24. By study design, patients in the long-term extension may have switched between the 50 mg and 100 mg golimumab doses at the discretion of the study physician. Table 5 Key efficacy outcomes from GO-RAISE. Placebo Golimumab 50 mg* n a 78 138 Responders, % of patients ASAS 20 Week 14 22% 59% Week 24 23% 56% ASAS 40 Week 14 15% 45% Week 24 15% 44% ASAS 5/6 Week 14 8% 50% Week 24 13% 49% * p ≤ 0.001 for all comparisons a n reflects randomised patients; actual number of patients evaluable for each endpoint may vary by timepoint Among patients remaining in the study and treated with golimumab, the proportion of patients with an ASAS 20 and ASAS 40 response were similar from week 24 through week 256. Statistically significant responses in BASDAI 50, 70 and 90 (p ≤ 0.017) were also seen at weeks 14 and 24. Improvements in key measures of disease activity were observed at the first assessment (week 4) after the initial golimumab administration and were maintained through week 24. Among patients remaining in the study and treated with golimumab, similar rates of change from baseline in BASDAI were observed from week 24 through week 256. Consistent efficacy was seen in patients regardless of use of DMARDs (MTX, sulfasalazine and/or hydroxychloroquine), HLA-B27 antigen status or baseline CRP levels as assessed by ASAS 20 responses at week 14. Golimumab treatment resulted in significant improvements in physical function as assessed by changes from baseline in BASFI at weeks 14 and 24. Health-related quality of life as measured by the physical component score of the SF-36 was also improved significantly at weeks 14 and 24. Among patients remaining in the study and treated with golimumab, improvements in physical function and health-related quality of life were similar from week 24 through week 256. Non-radiographic axial spondyloarthritis GO-AHEAD The safety and efficacy of golimumab were evaluated in a multi-centre, randomised, double-blind, placebo-controlled study (GO-AHEAD) in 197 adult patients with severe active nr-Axial SpA (defined as those patients meeting the ASAS classification criteria of axial spondyloarthritis but did not meet the modified New York criteria for AS). Patients enrolled in this study had active disease (defined as a BASDAI ≥ 4 and a Visual Analogue Scale (VAS) for total back pain of ≥ 4, each on a scale of 0-10 cm) despite current or previous NSAID therapy and had not previously been treated with any biological agents including anti-TNF therapy. Patients were randomly assigned to placebo or golimumab 50 mg administered subcutaneously every 4 weeks. At week 16, patients entered an open label period in which all patients received golimumab 50 mg administered subcutaneously every 4 weeks through week 48 with efficacy assessments performed through week 52 and safety follow-up through week 60. Approximately 93% of patients who were receiving golimumab at the beginning of the open-label extension (week 16) remained on treatment through the end of the study (week 52). Analyses were performed on both the All Treated (AT, N = 197) and Objective Signs of Inflammation (OSI, N = 158, defined by elevated CRP and/or evidence of sacroiliitis on MRI at baseline) populations. Placebo-controlled efficacy data were collected and analysed through week 16. The primary endpoint was the proportion of patients achieving ASAS 20 response at week 16. Key results are shown in Table 6 and described below. Table 6 Key efficacy outcomes from GO-AHEAD at week 16 Improvements in signs and symptoms All treated population (AT) Objective signs of inflammation population (OSI) Placebo Golimumab 50 mg Placebo Golimumab 50 mg n a 100 97 80 78 Responders, % of patients ASAS 20 40% 71%** 38% 77%** ASAS 40 23% 57%** 23% 60%** ASAS 5/6 23% 54%** 23% 63%** ASAS Partial Remission 18% 33%* 19% 35%* ASDAS-C b < 1.3 13% 33%* 16% 35%* BASDAI 50 30% 58%** 29% 59%** Inhibition of inflammation in sacroiliac (SI) joints as measured by MRI Placebo Golimumab 50 mg Placebo Golimumab 50 mg n c 87 74 69 61 Mean change in SPARCC d MRI sacroiliac joint score -0.9 -5.3** -1.2 -6.4** a n reflects randomised and treated patients b Ankylosing Spondylitis Disease Activity Score C-Reactive Protein (AT-Placebo, N = 90; AT-Golimumab 50 mg, N = 88; OSI-Placebo, N = 71; OSI-Golimumab 50 mg, N = 71) c n reflects number of patients with baseline and week 16 MRI data d SPARCC (Spondyloarthritis Research Consortium of Canada) ** p < 0.0001 for Golimumab vs placebo comparisons * p < 0.05 for Golimumab vs placebo comparisons Statistically significant improvements in signs and symptoms of severe active nr-Axial SpA were demonstrated in patients treated with golimumab 50 mg compared to placebo at week 16 (Table 6). Improvements were observed at the first assessment (week 4) after the initial golimumab administration. SPARCC score as measured by MRI showed statistically significant reductions in SI joint inflammation at week 16 in patients treated with golimumab 50 mg compared to placebo (Table 6). Pain as assessed by the Total Back Pain and Nocturnal Back Pain VAS, and disease activity as measured by ASDAS-C also showed statistically significant improvement from baseline to week 16 in patients treated with golimumab 50 mg compared to placebo (p < 0.0001). Statistically significant improvements in spinal mobility as assessed by BASMI (Bath Ankylosing Spondylitis Metrology Index) and in physical function as assessed by the BASFI were demonstrated in golimumab 50 mg-treated patients as compared to placebo-treated patients (p < 0.0001). Patients treated with golimumab experienced significantly more improvements in health-related quality of life as assessed by ASQoL, EQ-5D, and physical and mental components of SF-36, and experienced significantly more improvements in productivity as assessed by greater reductions in overall work impairment and in activity impairment as assessed by the WPAI questionnaire than patients receiving placebo. For all of the endpoints described above, statistically significant results were also demonstrated in the OSI population at week 16. In both the AT and OSI populations, the improvements in signs and symptoms, spinal mobility, physical function, quality of life, and productivity observed at week 16 among patients treated with golimumab 50 mg continued in those remaining in the study at week 52. GO-BACK The efficacy and safety of continued golimumab treatment (full or reduced dosing frequency) compared with treatment withdrawal was assessed in adult patients (18-45 years of age) with active nr-axSpA who demonstrated sustained remission during 10 months of monthly treatment with open-label golimumab (GO-BACK). Eligible patients (who achieved a clinical response by Month 4 and an inactive disease status (ASDAS < 1.3) at both Months 7 and 10) entering the double-blind withdrawal phase were randomised to continued monthly treatment with golimumab (full-treatment regimen, N = 63), every 2-month treatment with golimumab (reduced treatment regimen, N = 63) or monthly placebo treatment (treatment withdrawal, N = 62) for up to approximately 12 months. The primary efficacy endpoint was the proportion of patients without a flare of disease activity. Patients who experienced a flare, i.e., had an ASDAS collected at 2 consecutive assessments that both showed either an absolute score of ≥ 2.1 or post-withdrawal increase of ≥ 1.1 relative to Month 10 (end of open-label period), reinitiated monthly golimumab in an open-label retreatment phase to characterise clinical response. Clinical response after double-blind treatment withdrawal Among the 188 patients with inactive disease who received at least one dose of double-blind treatment, a significantly (p < 0.001) greater proportion of patients did not experience a disease flare when continuing golimumab with either the full-treatment (84.1%), or reduced treatment (68.3%) regimens compared with treatment withdrawal (33.9%) (Table 7). Table 7 Analysis of the proportion of participants without a flarea Full analysis set population (Period 2 – Double-blind) Treatment n/N % Difference in % vs Placebo Estimate (95% CI) b p-Value b GLM SC QMT 53/63 84.1 50.2 (34.1, 63.6) < 0.001 GLM SC Q2MT 43/63 68.3 34.4 (17.0, 49.7) < 0.001 Placebo 21/62 33.9 Full Analysis Set includes all randomised participants who attained inactive disease in period 1 and received at least one dose of blinded study treatment. a Defined as ASDAS at 2 consecutive visits that both show either absolute score ≥ 2.1 or post-withdrawal increase of ≥ 1.1 relative to Month 10 (Visit 23). b Type I error rate over the multiple treatment comparisons (GLM SC QMT vs Placebo and GLM SC Q2MT vs Placebo) was controlled using a sequential (step-down) testing procedure. Derived based on the stratified Miettinen and Nurminen method with CRP level (> 6 mg/L or ≤ 6 mg/L) as stratification factor. Participants who discontinued period 2 prematurely and prior to a 'flare' will be counted as having a 'flare'. N = Total number of participants; n = number of participants without a flare; GLM = golimumab; SC = subcutaneous, QMT = monthly dosing; Q2MT = every other month dosing. The difference in time-to-first flare between the treatment withdrawal group and either of the golimumab Treatment groups is shown in Figure 1 (log-rank p < 0.0001 for each comparison). In the placebo group, flares started approximately 2 months after golimumab was withdrawn, with the majority of flares occurring within 4 months of treatment withdrawal (Figure 1). Figure 1: Kaplan-Meier Analysis of Time-to-First Flare Clinical response to retreatment for a disease flare Clinical response was defined as a BASDAI improvement of ≥ 2 or ≥ 50% relative to the mean of the 2 consecutive BASDAI scores ascribed to the disease flare. Of the 53 participants in the reduced dosing or treatment withdrawal regimens who had a confirmed disease flare, 51 (96.2%) attained a clinical response to golimumab within the first 3 months of retreatment, although fewer patients (71.7%) were able to sustain it for all 3 months. Ulcerative colitis The efficacy of golimumab was evaluated in two randomised, double-blind, placebo-controlled clinical studies in adult patients. The induction study (PURSUIT-Induction) evaluated patients with moderately to severely active ulcerative colitis (Mayo score 6 to 12; Endoscopy subscore ≥ 2) who had an inadequate response to or failed to tolerate conventional therapies, or were corticosteroid dependent. In the dose confirming portion of the study, 761 patients were randomised to receive either 400 mg golimumab SC at week 0 and 200 mg at week 2, 200 mg golimumab SC at week 0 and 100 mg at week 2, or placebo SC at weeks 0 and 2. Concomitant stable doses of oral aminosalicylates, corticosteroids, and/or immunomodulatory agents were permitted. The efficacy of golimumab through week 6 was assessed in this study. The results of the maintenance study (PURSUIT-Maintenance) were based on evaluation of 456 patients who achieved clinical response from previous induction with golimumab. Patients were randomised to receive golimumab 50 mg, golimumab 100 mg or placebo administered subcutaneously every 4 weeks. Concomitant stable doses of oral aminosalicylates, and/or immunomodulatory agents were permitted. Corticosteroids were to be tapered at the start of the maintenance study. The efficacy of golimumab through week 54 was assessed in this study. Patients who completed the maintenance study through week 54 continued treatment in a study-extension, with efficacy evaluated through week 216. Efficacy evaluation in the study extension was based on changes in corticosteroid use, Physician's Global Assessment (PGA) of disease activity, and improvement in quality of life as measured by Inflammatory Bowel Disease Questionnaire (IBDQ). Table 8 Key efficacy outcomes from PURSUIT - Induction and PURSUIT – Maintenance PURSUIT-Induction Placebo N = 251 Golimumab 200/100 mg N = 253 Percentage of patients Patients in clinical response at week 6 a 30% 51%** Patients in clinical remission at week 6 b 6% 18%** Patients with mucosal healing at week 6 c 29% 42%* PURSUIT-Maintenance Placebo d N = 154 Golimumab 50 mg N = 151 Golimumab 100 mg N = 151 Percentage of patients Maintenance of response (Patients in clinical response through week 54) e 31% 47%* 50%** Sustained remission (Patients in clinical remission at both week 30 and week 54) f 16% 23% g 28%* N = number of patients ** p ≤ 0.001 * p ≤ 0.01 a defined as a decrease from baseline in the Mayo score by ≥ 30% and ≥ 3 points, accompanied by a decrease in the rectal bleeding subscore of ≥ 1 or a rectal bleeding subscore of 0 or 1. b Defined as a Mayo score ≤ 2 points, with no individual subscore > 1 c Defined as 0 or 1 on the endoscopy subscore of the Mayo score. d Golimumab induction only. e Patients were assessed for UC disease activity by partial Mayo score every 4 weeks (loss of response was confirmed by endoscopy). Therefore, a patient who maintained response was in a state of continuous clinical response at each evaluation through week 54. f A patient had to be in remission at both weeks 30 and 54 (without demonstrating a loss of response at any time point through week 54) to achieve durable remission. g In patients weighing less than 80 kg, a greater proportion of patients who received 50 mg maintenance therapy showed sustained clinical remission compared with those who received placebo. More golimumab-treated patients demonstrated sustained mucosal healing (patients with mucosal healing at both week 30 and week 54) in the 50 mg group (42%, nominal p < 0.05) and 100 mg group (42%, p < 0.005) compared with patients in the placebo group (27%). Among the 54% of patients (247/456) who were receiving concomitant corticosteroids at the start of PURSUIT-Maintenance, the proportion of patients who maintained clinical response through week 54 and were not receiving concomitant corticosteroids at week 54 was greater in the 50 mg group (38%, 30/78) and 100 mg group (30%, 25/82) compared with the placebo group (21%, 18/87). The proportion of patients who eliminated corticosteroids by week 54 was greater in the 50 mg group (41%, 32/78) and 100 mg group (33%, 27/82) compared with the placebo group (22%, 19/87). Among patients who entered the study extension, the proportion of subjects who remained corticosteroid free was generally maintained through week 216. Patients who did not achieve clinical response at week 6 in the PURSUIT-Induction studies were dosed golimumab 100 mg every 4 weeks in the PURSUIT-Maintenance study. At week 14, 28% of these patients achieved response defined by partial Mayo score (decreased by ≥ 3 points compared with start of induction). At week 54, the clinical outcomes observed in these patients were similar to the clinical outcomes reported for the patients achieving clinical response at week 6. At week 6, golimumab significantly improved quality of life as measured by change from baseline in a disease specific measure, IBDQ (inflammatory bowel disease questionnaire). Among patients who received golimumab maintenance treatment, the improvement in quality of life as measured by IBDQ was maintained through week 54. Approximately 63% of patients who were receiving golimumab at the beginning of the study extension (week 56), remained on treatment through the end of the study (last golimumab administration at week 212). Immunogenicity Anti-golimumab antibodies may develop during golimumab treatment. Formation of anti-golimumab antibodies may be associated with decreased systemic exposure to golimumab but no apparent correlation of antibody development with efficacy has been observed. The presence of antibodies to golimumab may increase the risk of injection site reactions (see section 4.8). Paediatric population The licensing authority has deferred the obligation to submit the results of studies with golimumab in one or more subsets of the paediatric population in ulcerative colitis (see section 4.2 for information on paediatric use).