Comparative efficacy of golimumab,infliximab, and adalimumab for moderately to severely active ulcerative colitis: a network meta-analysis accounting for differences in trial designs

Aim: To conduct a network meta-analysis (NMA) to establish the comparative efficacy of infliximab, adalimumab and golimumab for the treatment of moderately to severely active ulcerative colitis (UC). Design: A systematic literature search identified five randomized controlled trials for inclusion in the NMA. One trial assessed golimumab, two assessed infliximab and two assessed adalimumab. Outcomes included clinical response, clinical remission, mucosal healing, sustained clinical response and sustained clinical remission. Innovative methods were used to allow inclusion of the golimumab trial data given the alternative design of this trial (i.e., two-stage re-randomization). Results: After induction, no statistically significant differences were found between golimumab and adalimumab or between golimumab and infliximab. Infliximab was statistically superior to adalimumab after induction for all outcomes and treatment ranking suggested infliximab as the superior treatment for induction. Golimumab and infliximab were associated with similar efficacy for achieving maintained clinical remission and sustained clinical remission, whereas adalimumab was not significantly better than placebo for sustained clinical remission. Golimumab and infliximab were also associated with similar efficacy for achieving maintained clinical response, sustained clinical response and mucosal healing. Finally, golimumab 50 and 100 mg was statistically superior to adalimumab for clinical response and sustained clinical response, and golimumab 100 mg was also statistically superior to adalimumab for mucosal healing. Conclusion: The results of our NMA suggest that infliximab was statistically superior to adalimumab after induction, and that golimumab was statistically superior to adalimumab for sustained outcomes. Golimumab and infliximab appeared comparable in efficacy.     

Efficacy and safety of infliximab in steroid-dependent ulcerative colitis patients

BACKGROUND/AIMS: Limited data exist concerning infliximab administration in steroid-dependent ulcerative colitis (UC) patients. The aim of this study was to evaluate the efficacy and safety of infliximab in steroid-dependent disease. METHODOLOGY: Sixteen corticosteroid-dependent patients who received infusions of infliximab (5 mg/kg) at 0, 2 and 6 weeks and thereafter every 8 weeks (Group A), were compared with eight patients treated with methylprednisolone (0.8-1 mg/kg body weight) daily for three weeks followed by a tapering regimen up to the minimal dose to maintain a symptom-free condition (Group B). Steroid dependency was defined as recurrent flare-up on steroid reduction or withdrawal, or as the clinical need for steroid treatment twice within six consecutive months or three times within a year. Disease activity was assessed at recruitment, and clinical response was evaluated according to the two non-invasive indices [SEO and Simple Clinical Colitis Activity Index (SCCAI) scores]. RESULTS: In Group A, complete long-term response occurred in 68.75% and partial response in 18.75% of patients. Moreover, in the long-term follow-up, both SCCAI (10.37 +/- 2.27 vs. 3.31 +/- 2.65, p < 0.001) and SEO (209.33 +/- 13.6 vs. 123.3 +/- 34.8, p < 0.001) scores demonstrated a significant improvement. In group B, comparable features were also obtained regarding complete long-term (62.5%) and partial (25%) responses; both SCCAI (7.37 +/- 1.4 vs. 3.5 +/- 3.58, p = 0.039) and SEO (181.0 +/- 27.1 vs. 135.3 +/- 44.1, p = 0.038) scores also improved significantly. Six of eight patients in the methylprednisolone-treated group B developed Cushing-like symptoms. CONCLUSIONS: Infliximab appears to be a good alternative therapeutic regimen in steroid-dependent UC patients associated with long-term potential toxicity.     

Characteristics and therapeutic efficacy of sulfasalazine in patients with mildly and moderately active ulcerative colitis

AIM: To investigate the characteristics and short-term efficacy of sulfasalazine (SASP) in patients with mildly and moderately active ulcerative colitis (UC). METHODS: Two hundred and twenty-eight patients with mildly and moderately active UC were recruited, 106 patients in 1993-1995, and 122 patients in 2000-2002, they were assigned as the 1990s group (n - 106) and the 2000s group (n = 122), prospectively. The general characteristics, clinical manifestations, colonoscopic and histological data were compared between the two groups. The short-term efficacy and safety of SASP 3 g per d were evaluated. RESULTS: Between 2000s and 1990s groups, the gender ratio of men to women was 1:1.18 and 1:1.04, 57.4% and 50.9% of the patients were between 30 and 49 years old. The gender ratio and age of UC patients were not significantly different. The total course of 50.0% and 37.1% of UC patients was less than 1 year (P<0.05), 10.6% and 31.2% of the cases had a duration of more than 5 years (P<0.05) in 2000s and 1990s groups, respectively. The most common clinical type was first episode in 2000s group and chronic relapse in 1990s group. The patients showed a higher frequency of abdominal pain and tenderness in 1990s group than in 2000s group. Erosions were found in 84.4% and 67.9% of patients in 2000s and 1990s groups (P<0.05). Rough and granular mucosa (67.9% vs43.4%, P<0.05) and polyps (47.2% vs32.8%, P<0.05) were identified in 1990s group more than in 2000s group. There were no significant differences in clinical, colonoscopic and histological classifications. After SASP (1 g thrice per d) treatment for 6 wk, the clinical, colonoscopic and histological remission rates were 71.8%, 21.8% and 16.4%, respectively. In 79 patients with clinical remission, 58.2% and 67.1% remained grade 1 in colonoscopic and histological findings, respectively. The overall effects in first episode type (complete remission in 10, 18.9%, partial remission in 28, 52.8%, and improvement in 9, 17.0%) were better than in chronic relapse type (complete remission in 3, 7.5%; partial remission in 16, 40.0%; and improvement in 15, 37.5%) and chronic persistent type (complete remission in 1, 5.9%; partial remission in 6, 35.3%; and improvement in 6, 35.3%) respectively (P<0.05). In 110 patients treated with SASP, 18 patients (16.4%) had adverse reactions. Except for two cases of urticaria and one case of WBC decrease, none of the patients had to stop the treatment because of severe adverse reactions. CONCLUSION: Patients with mildly and moderately active UC in 2000s group had a shorter disease course, milder clinical manifestations, more first episode type and higher frequency of acute mucosal lesions in colonoscopy than in 1990s group. The patients in 1990s group had higher proportion of chronic relapse type and chronic mucosal change in colonoscopy than in 2000s group. The short-term efficacy of SASP could be mainly remission of clinical manifestations. But more than half of the patients still had light inflammation in colonoscopy and histology. The overall effects of SASP in first episode type were better than those in other types. SASP was a safe and effective drug to treat mildly and moderately active UC.     

Intravenous corticosteroids in moderately active ulcerative colitis refractory to oral corticosteroids

BackgroundOral corticosteroids remain the mainstay of treatment for moderately active ulcerative colitis (UC). In patients who fail to respond to oral corticosteroids, attempting the intravenous route before starting rescue therapies is an alternative, although no evidence supports this strategy.AimTo evaluate clinical outcomes after a course of intravenous corticosteroids for moderate attacks of UC according to the failed oral corticosteroids or not.MethodsAll episodes of active UC admitted to three university hospitals between January 2005 and December 2011 were identified and retrospectively reviewed. Only moderately active episodes treated with intravenous corticosteroids were included. Treatment outcome was compared between episodes which failed to outpatient oral corticosteroids for the index flare and those directly treated by intravenous corticosteroids.Results110 episodes were included, 45% of which failed to outpatient oral corticosteroids (median dose 60 mg/day [IQR 50–60], median length of course 10 days [IQR 7–17]). Initial response (defined as mild severity or inactive disease at day 7 after starting intravenous corticosteroids, without rescue therapy) was achieved in 75%, with no between-group differences (78% vs. 75%). After a median follow-up of 12 months (IQR 4–24), 35% of the initial responders developed steroid-dependency and up to 13% required colectomy. Unsuccessful response to oral corticosteroids was the only factor associated with steroid-dependency in the long term (P = 0.001).ConclusionsIntravenous corticosteroids are efficient for inducing remission in moderately active UC unresponsive to oral corticosteroids, but almost half of these patients develop early steroid-dependency. Alternative therapeutic strategies should be assessed in this clinical setting.     

Japanese pediatric patient with moderately active ulcerative colitis successfully treated with ustekinumab: A case report

Rationale:Ustekinumab is effective in the treatment of adult Crohn disease (CD) and ulcerative colitis (UC). However, data on its efficacy and safety in pediatric CD and UC are limited. To the best of our knowledge, there are no reports of Japanese children with UC treated with ustekinumab in the long-term.Patient concerns:A 14-year-old man with diarrhea and bloody stools was referred to our hospital. Colonoscopy revealed total colitis-type UC. His pediatric UC activity index score was 50, indicating moderately active UC.Diagnoses:Ulcerative colitis.Interventions:Infliximab was introduced because of steroid-resistant refractory UC; however, secondary ineffectiveness was observed 17 months later. Therefore, ustekinumab was administered along with prednisolone (16 years of age).Outcomes:The patient achieved UC remission after ustekinumab treatment, leading to maintained remission without side effects.Lessons:To the best of our knowledge, this is the first pediatric case of moderately active UC successfully treated with ustekinumab in Japan. Ustekinumab combined with steroids is an effective and safe induction therapy for UC.     

Efficacy of intravenous cyclosporin in moderately severe ulcerative colitis refractory to steroids

OBJECTIVE: The efficacy of intravenous cyclosporin (CSA) in acute severe ulcerative colitis (UC) is well established. The aim of this study was to evaluate its efficacy in moderately severe colitis refractory to steroids. METHODS: Twenty-six patients (17 men, mean age 41 +/- 14 yr) with UC refractory to steroids treated with CSA were included in this study. Severity was defined according to Truelove criteria. A clinical activity score below 10 during 2 consecutive days defined clinical response. RESULTS: According to Truelove criteria, all patients had moderate UC. CSA was administered IV at a mean daily dose of 3.7 +/- 0,5 mg/kg until response and then orally for 3.5 +/- 2.6 months. A clinical response was achieved in 20/26 patients (76,9%) within 5.7 +/- 2.8 days (5/6 failures were treated by proctocolectomy). During a follow-up of 27.8 +/- 20.8 months, relapse rate was 60% (12/20): 7 patients underwent proctocolectomy and 5 had clinical remission with CSA retreatment (N=4) and steroids (N=1). At the end of follow-up, 12 patients (46%) were in clinical remission, 12 (46%) required colectomy, 1 had chronic active UC and 1 was lost of follow-up. The probability to avoid surgery was 52% at 78 months. The only factor associated with avoidance of surgery was concomitant treatment with azathioprine (P=0.007). Ten reversible adverse events occurred in 9 patients. CONCLUSION: This study shows that CSA is safe and effective in moderately severe steroid resistant UC. Concomitant treatment with azathioprine significantly decreases the rate of subsequent surgery. CSA may act as a "bridge" until the therapeutic action of azathioprine is achieved for maintenance treatment. These results should be further confirmed by a prospective controlled study.     

Unemployment and disability in patients with moderately to severely active Crohn's disease

GOALS: Unemployment and disability rates in Crohn's disease patients from the ACCENT I trial were assessed. Factors associated with employment and disability status were explored. BACKGROUND: Limited data regarding unemployment and disability status in patients with active Crohn's disease are available. STUDY: Baseline data were used to assess unemployment and disability rates. Logistic regression analysis examined factors that were associated with employment and disability status. Analysis of variance was used to compare quality of life. RESULTS: The baseline full-and part-time employment rates were 48% and 13%, respectively, with 39% of patients unemployed and 25% receiving disability compensation. Only 14% of 225 unemployed patients felt well enough to work if a job were available. Younger age, female gender, shorter disease duration, and prior bowel resection predicted a higher likelihood of unemployment. Younger age and female gender also predicted a higher likelihood of not being employed full-time. Prior bowel resection predicted a higher likelihood of receiving disability compensation. Quality of life (Inflammatory Bowel Disease Questionnaire, Short Form-36) scores were significantly higher in employed patients. CONCLUSIONS: Patients with moderately to severely active Crohn's disease had low employment and high disability rates. Given their economic importance, assessment of these outcomes should be integrated into future evaluations of therapy, including clinical trials.     

Efficacy and safety of golimumab 52-week maintenance therapy in Japanese patients with moderate to severely active ulcerative colitis: a phase 3, double-blind,randomized, placebo-controlled study-(PURSUIT-J study)

Journal of Gastroenterology - The global phase 3 studies of golimumab [PURSUIT-SC and PURSUIT-maintenance (M)], an anti-tumor necrosis factor-α (anti-TNFα) antibody, have demonstrated...     

Predictors of health-related quality of life in patients with moderate to severely active ulcerative colitis receiving biological therapy

Abstract

Background and aims: Patients with ulcerative colitis have reduced health-related quality of life compared to the general population. Current treatment strategy aims to reduce patients’ symptoms and increase health-related quality of life. We investigated which symptoms of ulcerative colitis correlate to decreased health-related quality of life.

Methods: Among 743 patients with moderate to severely active ulcerative colitis receiving biological therapy in a cross-sectional national study, we determined which disease-related symptoms, as measured by the Simple Clinical Colitis Activity Index, worsened health-related quality of life scores across the Short Health Scale dimensions, while adjusting for treatment, age, and clinical manifestation, and stratifying for sex, by means of multiple linear regression.

Results: Patients with active disease had decreased health-related quality of life compared to those with inactive disease (median 5.8 (range 4.5–7.5) vs. 2 (0.8–3.3)). Both sexes had decreased health-related quality of life in all dimensions for the symptoms: bowel frequency during daytime (0.37–0.86 and 0.46–0.84), urgency of defecation (0.54–0.79 and 0.49–0.65) and blood in stool (0.50–0.75 and 0.36–0.54) for men and women respectively. Women were more often negatively affected by bowel frequency during night-time (4 domains vs. 1) and arthritis (5 domains vs. 3). In non-stratified analysis female sex is an independent predictor of lower health-related quality of life for 3 domains (0.38–0.53).

Conclusions: Health-related quality of life was most prominently associated with bowel frequency during daytime, urgency of defecation, and blood in stool. Other symptoms associated for some health-related quality of life dimensions, and appear to vary between the sexes.     

Indirect comparison of vedolizumab and adalimumab for biologic-naive patients with ulcerative colitis

Aim: Indirect comparison of efficacy and safety of vedolizumab with adalimumab in biologic-naïve patients with moderate to severe ulcerative colitis (UC).

Methods: Vedolizumab is a gut-selective medication for moderate to severe UC. Since no comparative trials are available for direct comparison of vedolizumab vs adalimumab in UC, a systematic review of literature databases was conducted to identify randomized, placebo-controlled trials of the two drugs in patients with moderate to severe UC after failure of conventional treatment. Studies were screened for eligibility by two reviewers based on predefined inclusion criteria. Bucher’s adjusted indirect comparison was used to compare vedolizumab and adalimumab indirectly through placebo as common comparator.

Results: One vedolizumab study (GEMINI 1) and three adalimumab studies (ULTRA 1, ULTRA 2 and M10-447) met the eligibility criteria. Baseline characteristics of the included populations were similar in biologic-naïve UC patients across study arms. Although no statistically significant differences between treatments were found for induction efficacy endpoints, there was a trend toward a benefit of vedolizumab over adalimumab. There were also no significant differences between treatments for any maintenance efficacy endpoints, with no clear trend favoring either agent. Vedolizumab exhibited statistically superior maintenance safety compared with adalimumab, with significant reductions in risks of adverse events (relative risk 0.67 [95% confidence interval 0.57–0.80]; p?<?.0001), serious adverse events (0.20 [0.09–0.42]; p?<?.0001) and adverse events leading to discontinuation (0.14 [0.05–0.43]; p?=?.0006).

Conclusion: This analysis indicates that vedolizumab has comparable efficacy to adalimumab with improved safety in biologic-naïve patients with moderate to severe UC.     

Endoscopic findings can predict the efficacy of leukocytapheresis for steroid-naive patients with moderately active ulcerative colitis

AIM：To investigate the therapeutic usefulness of leukocytapheresis （LCAP; Cellsoba） in steroid-naive patients with moderately active ulcerative colitis （UC）. METHODS： Eighteen steroid-naive patients with moderately active UC received one LCAP session every week for fi ve consecutive weeks. RESULTS： The remission rate 8 weeks after the last LCAP session was 61.1% （11/18）. All three patients with deep ulcers showed worsening after LCAP. For the remaining 15 patients, who had erosions or geographic ulcers, the average clinical activity index （CAI） score dropped significantly from 9.4 to 3.8 eight weeks after the last LCAP session （t = 4.89, P = 0.001）. The average C-reactive protein （CRP） levels before and after LCAP were 1.2 mg/dL and 1.0 mg/dL, respectively. Of the patients with erosions, geographic ulcers, and deep ulcers, 100% （9/9）, 33.3% （2/6）, and 0% （0/3） were in remission 8 weeks after the last LCAP session, respectively （χ2 = 7.65, P 〈 0.005）. Forty- eight weeks after the last LCAP session, the remission rates for patients with erosions and geographic ulcers were 44.4% （4/9） and 16.7% （1/6）, respectively. Only one patient suffered a mild adverse event after LCAP （nausea）. CONCLUSION： LCAP is a useful and safe therapyfor steroid-naive UC patients with moderate disease activity. Moreover, the effi cacy of the treatment can be predicted on the basis of endoscopic fi ndings.     

Methylprednisolone acetate versus oral prednisolone in moderately active ulcerative colitis.

BACKGROUND: Patients with active ulcerative colitis are treated with corticosteroids. We compared the efficacy and safety of intramuscular depot preparation of methylprednisolone acetate with oral prednisolone in the treatment of moderately active ulcerative colitis. DESIGN: Open labeled, randomized, prospective, four-month study. METHODS: 40 patients with moderately active ulcerative colitis (activity index 150-220) were randomized into two groups. Group A (n=21) received methylprednisolone acetate (80 mg intramuscularly once weekly for 6 weeks). Group B (n=19) received oral prednisolone (40 mg/day) in a 'tailing-off' regimen. In addition, patients in both the groups received sulfasalazine. Patients were followed up at 1, 2, 3, 4, 8, 12 and 16 weeks. The primary measure of therapeutic response was activity index. An index of <150 was considered as clinical remission. Secondary efficacy was assessed by subjective evaluation of acceptability of treatment by the patient. RESULTS: After one week of treatment, the decrease in mean activity index was significantly more with oral prednisolone (p<0.05), and five 5 patients (23.8%) in Group A and 12 (63.2%) in Group B were in clinical remission (p<0.05). However, after 2 weeks and beyond, the mean activity index and the number of patients with clinical remission were comparable in the two treatment groups. CONCLUSIONS: Methylprednisolone acetate as a depot preparation and oral prednisolone are equally effective in inducing remission in patients with moderately active ulcerative colitis. Though symptomatic improvement is quicker with oral prednisolone, the remission rate with the two drugs was similar after 2 weeks of treatment.     

Efficacy and safety of stellate ganglion block in chronic ulcerative colitis

AIM To investigate the efficacy and safety of stellate ganglion block for the treatment of patients with chronic ulcerative colitis.METHODS A total of 120 randomly selected patients with chronic ulcerative colitis treated in Cangzhou Central Hospital from January 2014 to January 2016 were included in this study. These patients were divided into two groups: control group(n = 30), patients received oral sulfasalazine treatment; experimental group(n = 90), patients received stellate ganglion block treatment. Clinical symptoms and disease activity in these two groups were compared before and after treatment using endoscopy. Blood was collected from patients on day 0, 10, 20 and 30 after treatment. Enzyme-linked immunosorbent assay was performed to determine interleukin-8(IL-8) level. The changes in IL-8 level post-treatment in the two groups were compared using repeated measures analysis of variance.RESULTS After treatment, clinical symptoms and disease activity were shown to be alleviated by endoscopy in both the control and experimental groups. However, patients in the control group did not have obvious abdominal pain relief. In addition, the degree of pain relief in the experimental group was statistically better than that in the control group(P 0.05). Ten days after treatment, IL-8 level was found to be significantly lower in the experimental group than in the control group, and the difference was statistically significant(P 0.05). In addition, adverse events were significantly higher in the control group than in the experimental group, and the difference was statistically significant(χ~2 = 33.215, P = 0.000).CONCLUSION The application of stellate ganglion block effectively improves treatment efficacy in chronic ulcerative colitis, relieves clinical symptoms in patients, and reduces the level of inflammatory factors. Furthermore, this approach also had a positive impact on the disease to a certain extent.     

Granulocytapheresis in the treatment of patients with active ulcerative colitis

In recent years, considering the role of inflammatory processes and the involvement of the immune system in ulcerative colitis, granulocytapheresis, a technique for removing circulating leukocytes and preventing their migration into the intestinal mucosa, has been proposed for the treatment of acute ulcerative colitis. Initially introduced for the treatment of patients who did not respond to conventional therapy only, this new therapy may become a useful and safe method to induce clinical remission in patients with acute disease. This article will review the clinical applications and issues concerning the use of granulocytapheresis in ulcerative colitis.     

Cost-effectiveness of abatacept in patients with moderately to severely active rheumatoid arthritis and inadequate response to methotrexate

Objective. To assess cost–effectiveness of abatacept inpatients with moderately to severely active RA and inadequateresponse to MTX. Methods. We developed a simulation model to depict progressionof disability [in terms of the HAQ Disability Index (HAQ-DI)]in women aged 55–64 yrs with moderately to severely activeRA and inadequate response to MTX. At model entry, patientswere assumed to receive either only MTX or MTX plus abatacept.Patients were then tracked from model entry until death. Futurehealth-state utilities and medical-care costs (except studytherapy) were estimated based on predicted values of the HAQ-DI.The model was estimated using data from a Phase III clinicaltrial of abatacept plus various secondary sources. Cost–effectivenesswas expressed in terms of incremental cost (2006 US$) per quality-adjustedlife-year (QALY) gained over alternatively 10 yrs and a lifetime.Costs and health effects were both discounted at 3% annually. Results. Over 10 yrs, abatacept would yield 1.2 additional QALYs(undiscounted) per patient (4.6 vs 3.4 for MTX) at an incremental(discounted) cost of $51 426 ($103 601 vs $52 175, respectively);over a lifetime, corresponding figures were 2.0 QALYS (6.8 vs4.8) and $67 757 ($147 853 vs $80 096). Cost–effectivenesswas [mean (95% CI)] $47 910 ($44 641, $52 136) per QALY gainedover 10 yrs and $43 041 ($39 070, $46 725) per QALY gained overa lifetime. Findings were robust in sensitivity analyses. Conclusion. Abatacept is cost-effective by current standardsof medical practice in patients with moderately to severelyactive RA and inadequate response to MTX. KEY WORDS: Abatacept, Methotrexate, Rheumatoid arthritis, Outcomes, Cost–effectiveness Submitted 3 May 2007; revised version accepted 4 January 2008.