BACKGROUND: Starting biologic treatment early in the course of inflammatory bowel disease (IBD) may associate with higher efficacy, especially in Crohn's disease (CD).
METHODS: A systematic review and individual-patient-data meta-analysis of all placebo-controlled trials of biologics approved for IBD at study inception (Oct 2015), using Vivli data-sharing platform. The primary outcome was the proportional biologic/placebo treatment effect on induction-of-remission in patients with short-duration (≤18months) versus long-duration disease (>18months) analyzed separately for CD and ulcerative colitis (UC). We used meta-regression to examine the impact of patients' characteristics on the primary outcome. Study PROSPERO registration: CRD42018041961.
RESULTS: We included 25 trials, testing infliximab, adalimumab, certolizumab, golimumab, natalizumab or vedolizumab (6,168 CD, 3,227 UC patients). In CD, induction-of-remission rates were higher in pooled placebo and active arms' patients with short-disease duration≤18 months (41.4%, 244/589) compared with disease-duration>18months (29.8%, 852/2857, meta-analytically estimated OR=1.33, 95%CI:1.09-1.64). The primary outcome, proportional biologic/placebo treatment effect on induction-of-remission, was not different in short-duration disease ≤18 months (n= 589, OR 1.47, 95%CI:1.01-2.15) compared with longer disease-duration (n=2857, OR 1.43, 95%CI:1.19-1.72). In UC trials, both the proportional biologic/placebo remission-induction effect and the pooled biologic-placebo effect were stable regardless of disease duration. Primary outcome results remained unchanged when tested using alternative temporal cut-offs and when modelled for individual-patients' co-variates, including prior anti-TNFs exposure.
CONCLUSION: There are higher rates of induction-of-remission with biologics and with placebo in early CD, resulting in a treatment-to-placebo effect ratio which is similar across disease durations. No such relationships between disease-duration and outcomes is found in UC.
BACKGROUND & AIMS: It is not clear whether concomitant therapy with corticosteroids and anti-tumor necrosis factor (TNF) agents is more effective at inducing remission in patients with Crohn's disease (CD) than anti-TNF monotherapy. We aimed to determine whether patients with active CD receiving corticosteroids during induction therapy with anti-TNF agents had higher rates of clinical improvement than patients not receiving corticosteroids during induction therapy.
METHODS: We systematically searched the MEDLINE, Embase, and CENTRAL databases, through January 20, 2016, for randomized trials of anti-TNF agents approved for treatment of CD and identified 14 trials (5 of adalimumab, 5 of certolizumab, and 4 of infliximab). We conducted a pooled meta-analysis of individual patient and aggregated data from these trials. We compared data from participants who continued oral corticosteroids during induction with anti-TNF therapy to those treated with anti-TNF agents alone. The endpoints were clinical remission (CD activity index [CDAI] scores <150) and clinical response (a decrease in CDAI of 100 points) at the end of induction (weeks 4-14 of treatment).
RESULTS: We included 4354 patients who received induction therapy with anti-TNF agents, including 1653 [38.0%] who were receiving corticosteroids. The combination of corticosteroids and an anti-TNF agent induced clinical remission in 32.0% of patients, whereas anti-TNF monotherapy induced clinical remission in 35.5% of patients (odds ratio [OR], 0.93; 95% CI, 0.74-1.17). The combination of corticosteroids and an anti-TNF agent induced a clinical response in 42.7% of patients, whereas anti-TNF monotherapy induced a clinical response in 46.8% (OR 0.84; 95% CI, 0.73-0.96). These findings did not change with adjustment for baseline CDAI scores and concurrent use of immunomodulators.
CONCLUSIONS: Based on a meta-analysis of data from randomized trials of anti-TNF therapies in patients with active CD, patients receiving corticosteroids during induction therapy with anti-TNF agents did not have higher rates of clinical improvement compared with patients not receiving corticosteroids during induction therapy. Given these findings and the risks of corticosteroid use, clinicians should consider early weaning of corticosteroids during induction therapy with anti-TNF agents for patients with corticosteroid-refractory CD.
GOALS AND BACKGROUND: Ustekinumab (UST) is a monoclonal antibody inhibitor of IL-12/IL-23 approved for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). We conducted a meta-analysis to compare rates of adverse events (AEs) in randomized controlled trials (RCTs) of UST for all indications.
STUDY: A systematic search was performed of MEDLINE, Embase, and PubMed databases through November 2019. Study inclusion included RCTs comparing UST to placebo or other biologics in patients aged 18 years or older with a diagnosis of an autoimmune condition.
RESULTS: Thirty RCTs with 16,068 patients were included in our analysis. Nine thousand six hundred and twenty-six subjects were included in the UST vs placebo analysis. There was no significant difference in serious or mild/moderate AEs between UST and placebo with an OR of 0.83 (95% CI 0.66, 1.05) and 1.08 (95% CI 0.99, 1.18), respectively, over a median follow-up time of 16 weeks. In a sub-analysis of CD and UC trials, no difference in serious or mild/moderate AEs in UST versus placebo was seen.
CONCLUSIONS: UST was not associated with an increase in short-term risk of AEs.
Background: Crohn disease (CD) is a chronic inflammatory disease that affects quality of life. There are several drugs available for the treatment of CD, but their relative efficacy is unknown due to a lack of high-quality head-to-head randomized controlled trials. Aim: To perform a mixed comparison of the efficacy and safety of biosimilars, biologics and JAK1 inhibitors for CD. Methods: We searched PubMed, Web of Science, embase and the Cochrane Library for randomized controlled trials (RCTs) up to Dec. 28, 2020. Only RCTs that compared the efficacy or safety of biosimilars, biologics and JAK1 inhibitors with placebo or another active agent for CD were included in the comparative analysis. Efficacy outcomes were the induction of remission, maintenance of remission and steroid-free remission, and safety outcomes were serious adverse events (AEs) and infections. The Bayesian method was utilized to compare the treatments. The registration number is CRD42020187807. Results: Twenty-eight studies and 29 RCTs were identified in our systematic review. The network meta-analysis demonstrated that infliximab and adalimumab were superior to certolizumab pegol (OR 2.44, 95% CI 1.35–4.97; OR 2.96, 95% CI 1.57–5.40, respectively) and tofacitinib (OR 2.55, 95% CI 1.27–5.97; OR 3.10, 95% CI 1.47–6.52, respectively) and revealed the superiority of CT-P13 compared with placebo (OR 2.90, 95% CI 1.31–7.59) for the induction of remission. Infliximab (OR 7.49, 95% CI 1.85–34.77), adalimumab (OR 10.76, 95% CI 2.61–52.35), certolizumab pegol (OR 4.41, 95% CI 1.10–21.08), vedolizumab (OR 4.99, 95% CI 1.19–25.54) and CT-P13 (OR 10.93, 95% CI 2.10–64.37) were superior to filgotinib for the maintenance of remission. Moreover, infliximab (OR 3.80, 95% CI 1.49–10.23), adalimumab (OR 4.86, 95% CI 1.43–16.95), vedolizumab (OR 2.48, 95% CI 1.21–6.52) and CT-P13 (OR 5.15, 95% CI 1.05–27.58) were superior to placebo for steroid-free remission. Among all treatments, adalimumab ranked highest for the induction of remission, and CT-P13 ranked highest for the maintenance of remission and steroid-free remission. Conclusion: CT-P13 was more efficacious than numerous biological agents and JAK1 inhibitors and should be recommended for the treatment of CD. Further head-to-head RCTs are warranted to compare these drugs.
BACKGROUND & AIMS: There is debate over whether patients with inflammatory bowel diseases (IBD) treated with biologics that are not tumor necrosis factor antagonists (such as vedolizumab or ustekinumab) should receive concomitant treatment with immunomodulators. We conducted a meta-analysis to compare the efficacy and safety of concomitant immunomodulator therapy vs vedolizumab or ustekinumab monotherapy.
METHODS: In a systematic search of publications, through July 31, 2019, we identified 33 studies (6 randomized controlled trials and 27 cohort studies) of patients with IBD treated with vedolizumab or ustekinumab. The primary outcome was clinical benefit, including clinical remission, clinical response, or physician global assessment in patients who did vs did not receive combination therapy with an immunomodulator. Secondary outcomes were endoscopic improvement and safety. We performed random-effects meta-analysis and estimated odds ratio (OR) and 95% CIs.
RESULTS: Overall, combination therapy was not associated with better clinical outcomes in patients receiving vedolizumab (16 studies: OR, 0.84; 95% CI, 0.68-1.05; I2=13.9%; Q test P=.17) or ustekinumab (15 studies: OR, 1.1; 95% CI, 0.87-1.38; I2=11%; Q test P=.28). Results were consistent in subgroup analyses, with no difference in clinical remission or response in induction vs maintenance studies or in patients with Crohn's disease vs ulcerative colitis in studies of vedolizumab. Combination therapy was not associated with better endoscopic outcomes in patients receiving vedolizumab (3 studies: OR, 1.13; 95% CI, 0.48-2.68; I2=0; Q test P=.96) or ustekinumab (2 studies: OR, 0.58; 95% CI, 0.21-1.16; I2=47%; Q test P=.17). Combination therapy was not associated with an increase in adverse events during vedolizumab therapy (4 studies: OR, 1.17; 95% CI, 0.75-1.84; I2=0; Q test P=.110).
CONCLUSIONS: In a meta-analysis of data from studies of patients with IBD, we found that combining vedolizumab or ustekinumab with an immunomodulator is no more effective than monotherapy in induction or maintenance of remission.
The ongoing COVID-19 pandemic has raised concerns about the risk of SARS-CoV-2 infection in patients with Crohn’s disease (CD) and patients with ulcerative colitis (UC) taking immunosuppressants or biologics. We conducted a systematic review and meta-analysis to assess the risk of respiratory infections in patients with inflammatory bowel disease (IBD) treated with vedolizumab. We searched PubMed, EMBASE and Scopus to identify randomized controlled trials (RCT) comparing vedolizumab to placebo in patients with IBD. Outcomes were the rate of respiratory tract infections (RTI), upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) among patients receiving vedolizumab as compared with placebo. Pooled rates were reported as Odds Ratios (OR) with 95% Confidence Interval (CI). Eight RCT involving 3,287 patients (1873 CD and 1415 UC) were analyzed; 2,493 patients received vedolizumab and 794 received placebo. The rates of RTI and URTI were statistically higher in vedolizumab-treated patients compared to placebo [OR = 1.63; 95% CI (1.07–2.49); OR = 1.64 95% CI (1.07–2.53) respectively]. UC patients, but not CD patients, receiving vedolizumab had a higher risk to develop RTI and URTI [OR = 1.98; 95% CI (1.41–2.77); OR = 2.02; 95% CI (1.42–2.87)] compared to placebo-treated patients. The number of LRTI was small in both treatment groups. Data confirm the good safety profile of vedolizumab even though RTI were more frequent in patients receiving vedolizumab and the risk of URTIs was significantly higher in patients with UC.
Background: Fatigue is a common and burdensome symptom experienced by individuals with inflammatory bowel disease (IBD). The subjective, complex nature of fatigue can often hamper its’ management, and the effectiveness of treatments for fatigue in IBD remains unknown. The aim of this Cochrane review was to assess the efficacy and safety of pharmacological and non-pharmacological interventions for managing fatigue in IBD. Methods: A systematic search was conducted up to July 2018, and the search was rerun in October 2019. All randomised controlled trials (RCTs) of pharmacological and non-pharmacological interventions in children or adults with IBD, where fatigue was assessed as a primary or secondary outcome were included. Data were extracted and study quality was independently assessed by two authors. Standard Cochrane methodological procedures were used. Results: Fourteen RCTs were included (3741 participants; all adults; 6 in Crohn’s disease (CD); 2 in ulcerative colitis (UC); 6 in both CD and UC), with five potentially relevant studies identified from the updated search (to be assessed for inclusion at the next update). The interventions varied widely and included nine pharmacological trials, four non-pharmacological trials, and one multimodular trial. Only four trials were designed specifically as interventions for managing fatigue and one meta-analysis was possible, due to the diversity and limited number of studies for each intervention. We found that adalimumab 40mg administered every other week (only for those known to respond to adalimumab induction therapy), self-directed stress management and physical activity advice may reduce fatigue but the evidence is very uncertain. The evidence suggest ferric maltol results in a slight increase in fatigue and electroacupuncture may result in a large reduction in fatigue and increase in quality of life. There is no evidence of effect for adalimumab maintenance therapy, adalimumab administered 40mg weekly, agaricus blazei murill-based mushroom extract, omega 3, guided stress management or cognitive behavioural therapy that is likely to have a clinically meaningful improvement on fatigue. Reporting in some of the trials was insufficient to assess the efficacy and safety of some therapies, including vitamin D3 supplementation, ferumoxytol, vedolizumab, tight control customised management and solution focused therapy. Conclusions: The effects of pharmacological and non-pharmacological interventions on fatigue in individuals with IBD are uncertain. It is difficult to draw firm conclusions regarding the efficacy and safety of interventions, as there is insufficient quantity and quality of evidence available. Further RCTs with larger number of participants are required to assess the potential benefits and harms of therapies, particularly interventions specifically designed for fatigue management.
BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, and immune response modulation is the main treatment strategy to induce remission in active CD. Certolizumab pegol (CZP) is a tumor necrosis factor-alfa (TNF-α) inhibitor which regulates impaired immune response.
OBJECTIVES: The primary objectives were to evaluate the efficacy and safety of CZP for the induction of remission in CD.
SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD group specialized register, trials registers and other sources from inception to 28 January 2019. Moreover, we contacted the pharmaceutical company that manufactures CZP.
SELECTION CRITERIA: We included randomized controlled trials comparing CZP with placebo or no treatment in active CD patients.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The main outcomes selected for GRADE analysis were clinical remission at week 8 (Crohn's Disease Activity Index [CDAI] ≤150), clinical response at week 8 (CDAI reduction ≥ 100 or clinical remission), and serious adverse events. The Mantel-Haenszel random-effects method was applied for the statistical analyses. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI).
MAIN RESULTS: Four studies involving 1485 participants with moderate to severe CD met the inclusion criteria and were used in the meta-analyses. All studies included active CD patients with CDAI ranging from 220 to 450. Most patients were adults over 18 years of age. One study was identified as high risk of bias due to a non-identical placebo while the other studies were judged to be at low risk of bias.CZP (100 mg to 400 mg every 2 to 4 weeks) was shown to be superior to placebo for achieving clinical remission at week 8 (RR 1.36, 95% CI 1.11 to 1.66; moderate certainty evidence). The raw numbers of participants achieving clinical remission at week 8 were 26.9% (225/835) and 19.8% (129/650) in the CZP and the placebo groups, respectively.CZP was shown to be superior to placebo for achieving clinical response at week 8 (RR 1.29, 95% CI 1.09 to 1.53; moderate certainty evidence). In raw numbers, clinical response at week 8 was achieved in 40.2% (336/835) and 30.9% (201/650) of participants in the CZP and the placebo groups, respectively.In raw numbers, serious adverse events were observed in 8.7% (73/835) and 6.2% (40/650) of participants in the CZP and the placebo groups, respectively (RR 1.35, 95% CI 0.93 to 1.97; moderate certainty evidence). Serious adverse events included worsening Crohn's disease, infections, and malignancy.
AUTHORS' CONCLUSIONS: Moderate certainty evidence suggests that CZP is effective for induction of clinical remission and clinical response in participants with active CD patients. It is uncertain whether the risk of serious adverse events differs between CZP and placebo as the 95% CI includes the possibility of a small decrease or doubling of events. Future studies are needed to evaluate the long-term efficacy and safety of CZP in CD patients.
BACKGROUND & AIMS: Fistulas are debilitating complications of Crohn's disease (CD) that affect up to 50% of patients. We conducted a systematic review and meta-analysis of randomized controlled trials to assess the efficacy of treatments for fistulizing CD.
METHODS: We searched publication databases from inception through December 13, 2016 for trials comparing the efficacy of a therapeutic agent (single or combination) with placebo or another active therapy in adult patients with any form of fistulizing CD. The Cochrane risk of bias tool was used to assess the methodological quality of trials; the overall quality of evidence was evaluated using GRADE. Primary outcomes included induction and maintenance of fistula response and remission. Pooled risk ratios (RRs) and 95% CIs were calculated for each outcome.
RESULTS: We analyzed data from 27 trials; most studies (21/27) focused on patients with perianal fistulizing CD. We found moderate-quality evidence to support the efficacy of tumor necrosis factor (TNF) antagonists (RR, 2.01; 95% CI, 1.36-2.97), particularly infliximab, ustekinumab (RR, 1.77; 95% CI, 0.93-3.37), and mesenchymal stem cell therapy (RR, 1.31; 95% CI, 0.98-1.73) for induction of fistula remission. We found low-quality evidence for the efficacy of vedolizumab and immunosuppressives. There was also low-quality evidence to support the efficacy of combination therapy with TNF antagonists and antibiotics vs a TNF antagonist alone.
CONCLUSION: In a systematic review and meta-analysis of 27 controlled trials, we found TNF antagonists to be effective for induction and maintenance of perianal fistula response and remission. There are few data on the effects on internal fistulae. Further studies are needed, particularly for ustekinumab, vedolizumab, and stem cell therapies, in patients with fistulizing CD.
BACKGROUND: This systematic review update summarizes the current evidence on the use of natalizumab for induction of remission in Crohn's disease (CD).
OBJECTIVES: To determine the efficacy and safety of natalizumab for induction of remission in CD.
SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Trials Register, and clinicaltrials.gov from inception to 10 May 2018.
SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing natalizumab to a placebo or control therapy for induction of remission in CD.
DATA COLLECTION AND ANALYSIS: Two authors independently screened studies, extracted data and assessed methodological quality using the Cochrane risk of bias tool. The primary outcome was failure to enter clinical remission. Secondary outcomes included clinical response, mean change in Crohn's Disease Activity Index (CDAI), adverse events (AEs), withdrawal due to AEs and serious AEs. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (95% CI). For continuous outcomes we calculated the mean difference (MD) and 95% CI. Data were pooled for meta-analysis when the interventions, patient groups and outcomes were sufficiently similar (determined by consensus). We used GRADE to assess the overall quality of the evidence.
MAIN RESULTS: A total of five RCTs (1771 participants) were included. Four studies (1692 participants) compared one, two or three infusions of natalizumab (300 mg or 3 mg/kg or 6mg/kg) to placebo. One study (79 participants) compared three infusions of natalizumab (300 mg) and infliximab (5 mg/kg) to infliximab and placebo. Four studies were rated as low risk of bias. One study was rated as unclear risk of bias for selective reporting.One, two and three infusions of natalizumab were superior to placebo for induction of remission and clinical response. Infusions were administered at weeks zero, four and eight. After one infusion, 76% (849/1117) of natalizumab participants failed to enter remission at 4 weeks compared to 83% (411/494) of placebo participants (RR 0.91, 95% CI 0.86 to 0.96, 3 studies, GRADE high quality). At 4 weeks, the RR for clinical response was 0.78 (95% CI 0.66 to 0.92, 3 studies, 1611 participants, GRADE moderate quality). After two infusions, after 8 weeks, 66% (693/1049) of natalizumab participants failed to enter remission compared to 77% (382/494) of placebo participants (RR 0.85, 95% CI 0.76 to 0.95; 3 studies, GRADE moderate quality). At 8 weeks, the RR for clinical response was 0.73 (95% CI 0.58 to 0.91, 3 studies, 1543 participants, GRADE low quality). After three infusions, at 12 weeks, 61% (596/983) of natalizumab participants failed to enter remission compared to 73% (313/431) of placebo participants (RR 0.85, 95% CI 0.78 to 0.92, 2 studies, GRADE high quality). At 12 weeks, the RR for clinical response was 0.76 (95% CI 0.67 to 0.86, 2 studies, 1414 participants, GRADE high quality). One study (507 participants) reported on change in CADI from baseline. Natalizumab participants had a larger drop in mean CDAI scores than placebo participants at 4, 8 and 12 weeks.The rates of AEs, withdrawals due to AEs and serious AEs were similar across groups at 4, 8 and 12 weeks. After one infusion, 74% (50/68) of natalizumab participants experienced an AE compared to 81% (51/63) of placebo participants (RR 0.91, 95% CI 0.75 to 1.09, GRADE moderate quality). Withdrawal due to an AE occurred in 1% (1/68) of natalizumab participants and 3% of placebo participants (RR 0.46, 95% CI 0.04 to 4.98, GRADE low quality). SAEs occurred in 10% (7/68) of natalizumab participants compared to 11% (7/63) of placebo participants (RR 0.93, 95% CI 0.34 to 2.49, GRADE low quality). After two infusions, 86% (57/66) of natalizumab participants experienced an AE compared to 81% (51/63) of placebo participants (RR 1.07, 95% CI 0.92 to 1.24, GRADE moderate quality). Withdrawal due to an AE occurred in 3% (2/66) natalizumab participants compared to 3% (2/63) placebo participants (RR 0.95, 95% CI 0.14 to 6.57, GRADE low quality). SAEs occurred in 9% (6/66) of natalizumab participants and 11% (7/63) of placebo participants (RR 0.82, 95% CI 0.29 to 2.30, GRADE low quality). After three infusions, 86% (848/984) of natalizumab participants experienced an AE compared to 83% (359/431) placebo participants (RR 1.03, 95% CI 0.98 to 1.08, GRADE high quality). Withdrawals due to AEs occurred in 8% (82/984) of natalizumab participants compared to 10% (45/431) of placebo participants (RR 0.86, 95% CI 0.59 to 1.26, GRADE moderate quality). SAEs occurred in 7% (65/983) of natalizumab participants and 8% (36/431) of placebo participants (RR 0.76. 95% CI 0.37 to 1.56, GRADE low quality). Adverse events included headache, nausea, nasopharyngitis, abdominal pain, fatigue, vomiting, and exacerbation of CD.The study comparing combination therapy with natalizumab and infliximab to infliximab and placebo demonstrated similar remission rates at 10 weeks. Sixty-four per cent (33/52) of participants assigned to natalizumab and infliximab failed to achieve remission compared to 70% (19/27) assigned to placebo and infliximab (RR 0.90, 95% CI 0.65 to 1.24, GRADE moderate quality). The rates of AEs (moderate quality evidence), withdrawals due to AEs (low quality evidence) and serious AEs (low quality evidence) were similar across groups at 10 weeks. Adverse events included headache, exacerbation of CD, nausea, and nasopharyngitis.Natalizumab is associated with the development of progressive multifocal leukoencephalopathy (PML) resulting in some patient deaths. There are currently no tests which can reliably predict those at risk of developing PML.
AUTHORS' CONCLUSIONS: High quality data suggest that natalizumab is effective for induction of clinical remission and response in some patients with moderately to severely active CD. However, none of the included studies had the power to detect rare but serious adverse events such as PML. Due to the association with PML, and the availability of alternative agents that are not associated with PML, natalizumab is not likely to be used in patients who fail currently available medical therapy. The use of natalizumab in select patients (e.g. patients allergic to different biologics) needs to be carefully considered against the potential risk of developing PML. Futher studies of natalizumab are not likely to be done.
Starting biologic treatment early in the course of inflammatory bowel disease (IBD) may associate with higher efficacy, especially in Crohn's disease (CD).
METHODS:
A systematic review and individual-patient-data meta-analysis of all placebo-controlled trials of biologics approved for IBD at study inception (Oct 2015), using Vivli data-sharing platform. The primary outcome was the proportional biologic/placebo treatment effect on induction-of-remission in patients with short-duration (≤18months) versus long-duration disease (>18months) analyzed separately for CD and ulcerative colitis (UC). We used meta-regression to examine the impact of patients' characteristics on the primary outcome. Study PROSPERO registration: CRD42018041961.
RESULTS:
We included 25 trials, testing infliximab, adalimumab, certolizumab, golimumab, natalizumab or vedolizumab (6,168 CD, 3,227 UC patients). In CD, induction-of-remission rates were higher in pooled placebo and active arms' patients with short-disease duration≤18 months (41.4%, 244/589) compared with disease-duration>18months (29.8%, 852/2857, meta-analytically estimated OR=1.33, 95%CI:1.09-1.64). The primary outcome, proportional biologic/placebo treatment effect on induction-of-remission, was not different in short-duration disease ≤18 months (n= 589, OR 1.47, 95%CI:1.01-2.15) compared with longer disease-duration (n=2857, OR 1.43, 95%CI:1.19-1.72). In UC trials, both the proportional biologic/placebo remission-induction effect and the pooled biologic-placebo effect were stable regardless of disease duration. Primary outcome results remained unchanged when tested using alternative temporal cut-offs and when modelled for individual-patients' co-variates, including prior anti-TNFs exposure.
CONCLUSION:
There are higher rates of induction-of-remission with biologics and with placebo in early CD, resulting in a treatment-to-placebo effect ratio which is similar across disease durations. No such relationships between disease-duration and outcomes is found in UC.
