scholarly journals DOP16 An evaluation of the exposure–efficacy relationship for subcutaneous vedolizumab maintenance treatment of Crohn’s disease: Pharmacokinetic findings from VISIBLE 2

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S056-S057
Author(s):  
C Chen ◽  
M Rosario ◽  
D Polhamus ◽  
N Dirks ◽  
W Zhang ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Maintenance Treatment ◽  
Activity Index ◽  
Controlled Trial ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Concentrations ◽  
Efficacy Outcome

Abstract Background The exposure–efficacy relationship and immunogenicity rates of the new vedolizumab subcutaneous (SC) formulation have been established for maintenance treatment of ulcerative colitis (UC).1 Here, we report vedolizumab SC exposure–efficacy and immunogenicity in Crohn’s disease (CD). Methods VISIBLE 2 (NCT02611817; EudraCT 2015-000481-58) was a pivotal, phase 3, randomised, double-blind, placebo-controlled trial evaluating the efficacy and safety of vedolizumab SC (108 mg every 2 weeks) as maintenance treatment in patients with moderately to severely active CD. Following intravenous (IV) vedolizumab (300 mg Week 0 and 2) induction, patients with a clinical response at Week 6 (≥70-point decrease in CD activity index [CDAI] from Week 0) were randomised to blinded maintenance treatment and included in the analyses. Vedolizumab serum concentrations were measured prior to dosing using an enzyme-linked immunosorbent assay. Immunogenicity was assessed with a drug-tolerant electrochemiluminescence assay. Predicted vedolizumab trough concentrations at Week 52 were grouped by quartiles (Q), and Week 52 efficacy outcome rates calculated for each Q. Missing efficacy outcome data were imputed as failures. Efficacy outcomes were clinical remission (CDAI ≤150) and enhanced clinical response (≥100-point decrease in CDAI from Week 0 at Week 52). Results Following vedolizumab IV induction (N = 644), patients with a clinical response were randomised and received vedolizumab SC (N = 275) or placebo (N = 134) as maintenance treatment. At Week 52, patients on vedolizumab SC maintenance had a positive exposure–efficacy relationship for clinical remission (Q1: 37.7%; Q4: 50.7%) and enhanced clinical response (Q1: 37.7%; Q4: 53.6%; Figures 1 and 2). Overall, 7/275 (2.5%) patients on vedolizumab SC (following vedolizumab IV induction) developed anti-vedolizumab antibodies (AVAs): 3/7 patients were persistently AVA positive and 4/7 had neutralising antibodies. Five of 7 AVA-positive patients on vedolizumab SC did not achieve clinical remission and enhanced clinical response at Week 52; 2 of those patients were persistently AVA-positive. Immunogenicity was not associated with injection-site reactions or hypersensitivity reactions. Conclusion These preliminary results suggest a trend for higher vedolizumab SC serum concentrations with greater efficacy in CD, but the association was less pronounced than was reported in UC. (1) The AVA rate was similar to what was observed in prior vedolizumab IV studies. (2) In this study, vedolizumab immunogenicity appeared to be associated with clinical outcome. References

scholarly journals OP23 Efficacy and safety of vedolizumab SC in patients with moderately to severely active Crohn’s disease: Results of the VISIBLE 2 study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S020-S021
Author(s):  
S Vermeire ◽  
W Sandborn ◽  
F Baert ◽  
S Danese ◽  
T Kobayashi ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Maintenance Treatment ◽  
Activity Index ◽  
Study Drug ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind

Abstract Background Vedolizumab (VDZ) is a gut-selective, humanised, monoclonal α 4β 7 integrin antibody for the treatment of patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD). VDZ is currently an intravenous (IV) therapy; a subcutaneous (SC) formulation is under development to provide patients with an alternative route of administration for maintenance treatment for UC and CD. Here we present the first data from the phase 3 study of VDZ SC maintenance treatment in CD. Methods VISIBLE 2 (NCT02611817; EudraCT 2015-000481-58) was a randomised, double-blind, placebo (PBO)-controlled phase 3 trial of VDZ SC as maintenance treatment in adults with moderately to severely active CD. Patients (n = 644) received open-label VDZ 300mg IV induction therapy at Weeks 0 and 2. At Week 6, clinical responders (defined as patients with a ≥70-point decrease in CD Activity Index [CDAI] from baseline) were randomly assigned to receive vedolizumab SC (108 mg every 2 weeks [Q2W]), or placebo (Q2W) for up to 52 weeks. The primary endpoint was clinical remission at Week 52 (defined as CDAI score ≤150). Rank-ordered secondary endpoints were enhanced clinical response at Week 52 (a drop of ≥100 in CDAI score), corticosteroid (CS)-free clinical remission at Week 52, and clinical remission at Week 52 in anti-tumour necrosis factor (TNF)-naïve patients. Finally, VDZ immunogenicity and predefined adverse events of special interest were assessed. Results Patients who responded to VDZ IV induction at Week 6 (n = 409) were randomised to VDZ SC (n = 275) or PBO (n = 134) maintenance and received at least 1 dose of study drug; 61% and 53%, respectively, were previously exposed to anti-TNF therapy. At Week 52, 48.0% of patients on VDZ SC vs. 34.3% on PBO were in clinical remission (p = 0.008, Figure). Enhanced clinical response at Week 52 was reached by 52.0% vs. 44.8% of patients on VDZ SC vs. PBO, respectively (p = 0.167). Among patients on concomitant CS at baseline (VDZ SC, n = 95; PBO, n = 44), 45.3% receiving VDZ SC vs. 18.2% receiving PBO achieved CS-free clinical remission at Week 52. Of anti-TNF-naïve patients (VDZ SC, n = 107; PBO, n = 63), 48.6% vs. 42.9% were in clinical remission at Week 52 in the VDZ SC and PBO arms, respectively. Injection-site reactions were reported for <3% of patients treated with VDZ SC. Serious infections, malignancy, and liver injury were ≤5% for both arms. Anti-VDZ antibodies were detected in 7 (2.5%) patients treated with VDZ SC arm; 4 of 7 patients developed neutralising antibodies. No new safety signals were observed. Conclusion Among VDZ IV induction responders, significantly more patients on maintenance VDZ SC than PBO achieved clinical remission at Week 52. The safety findings with VDZ SC remain in line with the known safety profile of VDZ IV in patients with CD.

scholarly journals OP26 Risankizumab induces early clinical remission and response in patients with Moderate-to-Severe Crohn’s Disease: Results from the phase 3 ADVANCE and MOTIVATE studies

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S026-S027
Author(s):  
S W Schreiber ◽  
M Ferrante ◽  
R Panaccione ◽  
J F Colombel ◽  
T Hisamatsu ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Induction Therapy ◽  
Clinical Remission ◽  
Activity Index ◽  
Unmet Need ◽  
Inadequate Response ◽  
Biologic Treatment ◽  
Double Blind

Abstract Background Present therapies leave an unmet need for early and effective treatment for patients with Crohn’s disease (CD). Risankizumab (RZB), a humanized immunoglobulin G1 monoclonal antibody against the p19 subunit of interleukin-23, was evaluated as an induction therapy to induce early clinical remission and response in patients with moderate-to-severe CD in two double-blind, randomized, placebo (PBO)-controlled studies (ADVANCE [NCT03104413] and MOTIVATE [NCT03105128]). Methods Patients with moderate-to-severe CD (CD Activity Index [CDAI] of 220–450, Simple Endoscopic Score for CD [SES-CD] ≥ 6 [≥ 4 for isolated ileal disease] excluding the narrowing component, and average daily [liquid/very soft] stool frequency [SF] ≥ 4 and/or average daily abdominal pain [AP] score ≥ 2) who had inadequate response or intolerance to conventional and/or biologic treatment (ADVANCE), or biologic treatment only (MOTIVATE) were randomised 2:2:1 (ADVANCE) or 1:1:1 (MOTIVATE) to receive intravenous RZB 600 mg, RZB 1200 mg, or PBO as induction therapy at weeks 0, 4, and 8. Clinical remission (per either CDAI or a composite of SF and AP criteria), clinical response (per CDAI criterion), and enhanced clinical response (per a composite of SF and AP criteria) were evaluated at weeks 4, 8, and 12 (endpoints defined in Figure 1 footnotes). Safety was assessed throughout the studies. Results A total of 1419 patients from ADVANCE (N = 850) and MOTIVATE (N = 569) respectively, were randomised and included in the intention-to-treat population. In both studies, starting at week 4 (the first prespecified measurement), greater proportions of RZB 600 mg or RZB 1200 mg- vs PBO-treated patients achieved clinical remission per either CDAI (P = .01/P < .05) or SF/AP criteria (P < .01/P < .01), clinical response per CDAI criterion (P = .001/P < .01), and enhanced clinical response per SF/AP criteria (P < .01/P = .14) (Figure 1). For both RZB 600 mg and RZB 1200 mg, the efficacy and treatment effect increased through week 12 (P ≤ .001/P ≤ .001) (Figure 1). Treatment with RZB 600 mg or 1200 mg was well tolerated, and no new safety risks were identified.1,2 Conclusion Induction therapy with both RZB 600 mg and 1200 mg intravenous resulted in significantly greater clinical remission and response vs PBO as early as week 4 and sustained through week 12 in patients with moderate-to-severe CD who had inadequate response or intolerance to conventional and/or biologic treatment. References

scholarly journals DOP13 Clinical and endoscopic response to ustekinumab in Crohn’s disease: Week 16 interim analysis of the STARDUST trial

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S049-S052 ◽  
Author(s):  
S Danese ◽  
S Vermeire ◽  
G D’Haens ◽  
J Panés ◽  
A Dignass ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Disease Duration ◽  
Activity Index ◽  
Standard Of Care ◽  
Treat To Target ◽  
Faecal Calprotectin ◽  
Intention To Treat

Abstract Background Treat-to-target (T2T) strategy may optimise IBD disease management. We describe interim clinical and endoscopic results of the STARDUST trial in Crohn’s disease (CD) patients, following 16 weeks (W) of ustekinumab (UST) induction. Methods STARDUST, an ongoing phase 3b randomised strategy trial, enrolled adults with moderate–severely active CD (CD activity index [CDAI] 220–450) and simple endoscopic index for CD [SES-CD] ≥3) who failed conventional therapy ±1 biologic. At W0, patients received intravenous, weight-based UST of ~6mg/kg (approved label) and at W8, subcutaneous UST 90mg. At W16, patients with CDAI reduction ≥70 points were randomised (1:1) to T2T or standard of care. Key endpoints (intention-to-treat [ITT] set, as observed) were analysed at W8 and W16: % patients in clinical remission (CDAI score <150); % patients with a clinical response (CDAI <150 or decrease vs. baseline [BL] ≥100 points); faecal calprotectin (FCal) and C-reactive protein (CRP) levels: normalisation of FCal or/and CRP; improvement ≥50% vs. BL (patients with elevated FCal and CRP subpopulations); change vs. BL in CDAI and Inflammatory Bowel Disease Questionnaire (IBDQ) total scores. Patients randomised to T2T underwent colonoscopy at W16 and were analysed for change in SES-CD score vs. BL, endoscopic response (decrease in SES-CD score ≥50% vs. BL) and endoscopic remission (SES-CD score ≤2) (central reading). Results The ITT full set included 500 patients with BL mean (SD) CDAI score 282.3 (65.8), SES-CD 13.1 (8.1), CRP 15.7 (23.4) mg/l, FCal 1741.9 (2932.1) mg/g and disease duration 9.4 (8.7) years; 58.4% previously failed 1 biologic. At W16, 79.4% of patients had a clinical response and 66.6% were in clinical remission. About half of the patients showed ≥50% improvement in FCal and CRP levels, which normalised in about 1/3 of patients. Results were similar irrespective of previous biologic (Table 1); 84% of patients in response at W16 were in clinical remission. Statistically significant changes from BL in CDAI, FCal, and CRP were observed at W8, and in IBDQ scores at W16 (Table 2). In the T2T set (n = 220; CDAI 70 responders), BL characteristics were similar to the full analysis set; SES-CD score was 13.4 (8.8). At W16, 36.8% and 11.4% of patients in the T2T set achieved endoscopic response and remission, respectively. The endoscopic response was independent of BL SES-CD score and disease duration, but numerically better for colonic vs. ileal disease. No new safety signals were reported. Conclusion STARDUST is the first T2T trial in CD patients. After 16 W following induction with UST, 2/3 of patients achieved clinical remission. Thirty-seven per cent of those randomised to the T2T arm (CDAI 70 responders) showed endoscopic response by central reading at W16. Results were similar irrespective of being bio-naïve or failing 1 biologic.

scholarly journals Infliximab Preferentially Induces Clinical Remission and Mucosal Healing in Short Course Crohn’s Disease with Luminal Lesions through Balancing Abnormal Immune Response in Gut Mucosa

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Lijuan Yu ◽  
Xuehua Yang ◽  
Lu Xia ◽  
Jie Zhong ◽  
Wensong Ge ◽  
...  
Keyword(s):  
Immune Response ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Disease Duration ◽  
Activity Index ◽  
Mucosal Healing ◽  
Short Course ◽  
Short Disease Duration

This study was undertaken to evaluate the efficacy of infliximab (IFX) in treatment of Crohn’s disease (CD) patients. 106 CD patients were undergoing treatment with IFX from five hospitals in Shanghai, China. Clinical remission to IFX induction therapy was defined as Crohn’s disease activity index (CDAI) < 150. Clinical response was assessed by a decrease in CDAI ≥ 70, and the failure as a CDAI was not significantly changed or increased. Ten weeks after therapy, 61 (57.5%) patients achieved clinical remission, 17 (16.0%) had clinical response, and the remaining 28 (26.4%) were failed. In remission group, significant changes were observed in CDAI, the Simple Endoscopic Score for Crohn’s Disease (SES-CD), and serum indexes. Patients with short disease duration (22.2 ± 23.2 months) and luminal lesions showed better effects compared to those with long disease duration (71.0 ± 58.2 months) or stricturing and penetrating lesions. IFX markedly downregulated Th1/Th17-mediated immune response but promoted IL-25 production in intestinal mucosa from remission group. No serious adverse events occurred to terminate treatment. Taken together, our studies demonstrated that IFX is efficacious and safe in inducing clinical remission, promoting mucosal healing, and downregulating Th1/Th17-mediated immune response in short course CD patients with luminal lesions.

scholarly journals Short-term tolerability and effectiveness of methotrexate monotherapy in adult patients with Crohn’s disease: a retrospective study

2021 ◽  
Vol 14 ◽  
pp. 175628482110430
Author(s):  
Hee Seung Hong ◽  
Kyuwon Kim ◽  
Kyunghwan Oh ◽  
Jae Yong Lee ◽  
Seung Wook Hong ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Oral Administration ◽  
Clinical Response ◽  
Activity Index ◽  
Medical Center ◽  
Retrospective Chart Review ◽  
Asian Population ◽  
Aminosalicylic Acid ◽  
Parenteral Injection

Introduction: Immunomodulators remain fundamental for the medical treatment of Crohn’s disease (CD). Methotrexate (MTX) is widely used as a second-line immunomodulator; however, there is a lack of recent data on MTX monotherapy among the Asian population with CD. Therefore, in this study, we aimed to investigate the tolerability and clinical outcomes of MTX in Korean patients with CD. Methods: A retrospective chart review was performed for CD patients treated with MTX monotherapy or in combination with 5-aminosalicylic acid (5-ASA), at the Asan Medical Center, Seoul, South Korea. The tolerability of MTX monotherapy within 6 months was assessed and the clinical effectiveness of MTX was evaluated based on the Crohn’s disease activity index (CDAI). Results: In total, 85 patients were included, of which 29 (34.1%) discontinued MTX due to intolerability during the follow-up. Adverse events (AEs) were reported in 41 (48.2%) patients. The most common AE was gastrointestinal disorders (17/41) and only one patient experienced a serious AE, a systemic infection that required hospitalization. Among the 56 patients who tolerated MTX within 6 months, 44 (65.9%) showed a clinical response. Moreover, no factor was significantly associated with intolerability. The administration method was the only factor significantly associated with a response to MTX ( p = 0.041). The adjusted odds ratio of parenteral injection compared to oral administration was 5.68 (95% confidence interval (CI), 1.07–30.08). Conclusion: In this study, one-third of patients were intolerant to MTX; nonetheless, the response rate was as high as 65.9% among tolerant patients. In addition, no significant factors affected intolerability. In terms of the clinical response, parenteral injection could be better than oral administration.

scholarly journals Epithelial Cell Biomarkers Are Predictive of Response to Biologic Agents in Crohn’s Disease

2020 ◽  
Author(s):  
Mark T Osterman ◽  
Kelli L VanDussen ◽  
Ilyssa O Gordon ◽  
Elisabeth M Davis ◽  
Katherine Li ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Epithelial Cell ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Predictive Value ◽  
Controlled Trial ◽  
Biologic Agents ◽  
Intestinal Epithelial ◽  
Randomized Controlled ◽  
Discriminant Ability

Abstract Background Therapeutic efficacy of biologics has remained at about 50% for 2 decades. In Crohn’s disease (CD) patients, we examined the predictive value of an epithelial cell biomarker, ileal microvillar length (MVL), for clinical response to ustekinumab (UST) and vedolizumab (VDZ) and its relationship to another biomarker, intestinal epithelial cell (IEC) pyroptosis, with respect to response to VDZ. Method Ileal biopsies from the UNITI-2 randomized controlled trial were analyzed for MVL as a predictor of clinical response to UST. In a 5-center academic retrospective cohort of CD patients, ileal MVL was analyzed to determine its predictive value for response to VDZ. Correlation between ileal MVL and IEC pyroptosis was determined, and the discriminant ability of the combination of 2 biomarkers to VDZ was examined. Results Clinical response in UST was significantly higher than placebo (65% vs 39%; P = 0.03), with patients with normal MVL (&gt;1.7 µm) having the greatest therapeutic effect: 85% vs 20% (P = 0.02). For VDZ, clinical response with MVL of 1.35 to 1.55 µm was 82% vs 44% (&lt;1.35 µm) and 40% (&gt;1.55 µm; P = 0.038). There was no correlation between ileal MVL and IEC pyroptosis. The combination criteria of ileal pyroptosis &lt;14 positive cells/1000 IECs or MVL of 1.35 to 1.55 µm could identify 84% of responders and 67% of nonresponders (P = 0.001). Conclusion Ileal MVL was predictive of response to UST and VDZ in prospective and retrospective CD cohorts. It was independent of ileal IEC pyroptosis, and combination of the 2 biomarkers enhanced the discriminate ability of responders from nonresponders to VDZ.

Ustekinumab serum concentrations are associated with clinical outcomes in Crohn’s disease – a regional multi-center pilot study

2020 ◽  
Vol 58 (05) ◽  
pp. 439-444 ◽  
Author(s):  
Anne Kerstin Thomann ◽  
Lucas-Alexander Schulte ◽  
Anna-Maria Globig ◽  
Peter Hoffmann ◽  
Thomas Klag ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Pilot Study ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Roc Curve ◽  
Response To Therapy ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Area Under Roc Curve

Abstract Background and aim The role of therapeutic drug monitoring (TDM) in ustekinumab (UST) therapy for Crohn’s disease (CD) has not been established, as only few studies have analyzed the relationship between UST serum concentrations and clinical outcome. In this pilot study, we retrospectively examined the potential of UST-concentrations (cUST) 8 weeks after induction (cUSTw8) to predict clinical response at week 16. Methods Serum samples and clinical data from patients (n = 72) with moderate to severely active CD who received intravenous induction with UST were retrospectively analyzed. cUST were quantitated using liquid chromatography-tandem mass spectrometry (LC-MSMS). A receiver-operating characteristic (ROC) curve and area under ROC curve (AUROC) was computed to analyze the predictive potential of cUSTw8 for clinical response at week 16 and to determine the minimal therapeutic UST trough concentration. Results Forty-four patients (61 %) achieved clinical response to UST therapy at week 16. cUSTw8 was moderately effective to predict clinical response with a minimal therapeutic cUSTw8 of 2.0 mg/l (AUC 0.72, p = 0.001). Conclusion Trough concentrations of UST 8 weeks after induction predict clinical response to therapy in week 16 with moderate sensitivity and specificity. TDM using LC-MSMS could prove beneficial in personalized UST therapy of patients with CD by identifying individuals with subtherapeutic concentrations who might benefit from dose escalation.

scholarly journals Epithelial cell biomarkers are predictive of response to biologic agents in Crohn’s disease

2020 ◽  
Author(s):  
Mark T. Osterman ◽  
Kelli L. VanDussen ◽  
Ilyssa O. Gordon ◽  
Elisabeth M. Davis ◽  
Katherine Li ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Epithelial Cell ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Predictive Value ◽  
Controlled Trial ◽  
Biologic Agents ◽  
Intestinal Epithelial ◽  
Randomized Controlled ◽  
Discriminant Ability

AbstractObjectiveTherapeutic efficacy of biologics has remained at about 50% for 2 decades. In Crohn’s disease (CD) patients, we examined the predictive value of an epithelial cell biomarker, ileal microvillar length (MVL), for clinical response to ustekinumab (UST) and vedolizumab (VDZ), and its relationship to another biomarker, intestinal epithelial cell (IEC) pyroptosis with respect to response to VDZ.DesignIleal biopsies from the UNITI-2 randomized controlled trial were analyzed for MVL as a predictor of clinical response to UST. In a 5-center academic retrospective cohort of CD patients, ileal MVL was analyzed to determine its predictive value for response to VDZ. Correlation between ileal MVL and IEC pyroptosis was determined, and the discriminant ability of the combination of two biomarkers to VDZ was examined.ResultsClinical response in UST was significantly higher than placebo (65% vs. 39%, p=0.03), with patients with normal MVL (>1.7 µm) having the greatest therapeutic effect: 85% vs. 20% (p=0.02). For VDZ, clinical response with MVL of 1.35-1.55 µm was 82% vs. 44% (<1.35 µm) and 40% (>1.55 µm) (p=0.038). There was no correlation between ileal MVL and IEC pyroptosis. The combination criteria of ileal pyroptosis < 14 positive cells/1000 IECs or MVL of 1.35-1.55 µm could identify 84% of responders and 67% of non-responders (p=0.001).ConclusionsIleal MVL was predictive of response to UST and VDZ in prospective and retrospective CD cohorts. It was independent of ileal IEC pyroptosis, combination of the two biomarkers enhanced the discriminate ability of responders from non-responders to VDZ.

Azithromycin and metronidazole versus metronidazole-based therapy for the induction of remission in mild to moderate paediatric Crohn’s disease : a randomised controlled trial

Gut ◽  
2018 ◽  
Vol 68 (2) ◽  
pp. 239-247 ◽  
Author(s):  
Arie Levine ◽  
Michal Kori ◽  
Jarek Kierkus ◽  
Rotem Sigall Boneh ◽  
Malgorzata Sladek ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Randomised Controlled Trial ◽  
Crohn's Disease ◽  
Activity Index ◽  
Controlled Trial ◽  
Open Label ◽  
Faecal Calprotectin ◽  
Group 2 ◽  
Randomised Controlled ◽  
Group 1

ObjectiveCrohn’s disease (CD) pathogenesis associated with dysbiosis and presence of pathobionts in the lumen, intracellular compartments and epithelial biofilms. Azithromycin is active in all three compartments. Our goal was to evaluate if azithromycin-based therapy can improve response and induce remission compared with metronidazole alone in paediatric CD.DesignThis blinded randomised controlled trial allocated children 5–18 years with 10<Pediatric Crohn’s Disease Activity Index (PCDAI)≤40 to azithromycin 7.5 mg/kg, 5 days/week for 4 weeks and 3 days/week for another 4 weeks with metronidazole 20 mg/kg/day (group 1) or metronidazole alone (group 2), daily for 8 weeks. Failures from group 2 were offered azithromycin as open label. The primary end point was response defined by a decrease in PCDAI>12.5 or remission using intention to treat analysis.Results73 patients (mean age 13.8±3.1 years) were enrolled, 35 to group 1 and 38 to group 2. Response and remission rates at week 8 were identical 23/35 (66%) in group 1 and 17/38 (45%) and 15/38 (39%) in group 2 (P=0.07 and P=0.025, respectively). The needed to treat for remission was 3.7. Faecal calprotectin declined significantly in group 1 (P=0.003) but not in group 2 (p=0.33), and was lower at week 8 (P=0.052). Additional therapy was required in 6/35(17%) from group 1 versus 16/38(42%) in group 2 (P=0.027) by week 8. Among 12 failures in group 2, open-label azithromycin led to remission in 10/12 (83%).ConclusionsThe combination of azithromycin and metronidazole failed to improve response but was superior for induction of remission and reduction in calprotectin.Trial registration numberNCT01596894.

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