Setyobudi AK, et al.
Safety and efficacy of ontamalimab.
Safety and efficacy of ontamalimab in inflammatory bowel disease: A systematic review and dose-response meta-analysis Assyadilla Kirana Setyobudi1.
Valentino Ryu Yudianto2.
Arisvia Sukma Hariftyani1.
Gatot Soegiarto3,4,5* Faculty of Medicine.
Universitas Airlangga Surabaya.
Indonesia, 2Faculty of Medicine.
Universitas Indonesia.
Jakarta.
Indonesia, 3Allergy and Clinical Immunology Division.
Department of Internal Medicine.
Dr.
Soetomo General Academic Hospital.
Surabaya.
Indonesia, 4Allergy and Clinical Immunology Division.
Department of Internal Medicine.
Faculty of Medicine.
Universitas Airlangga Surabaya.
Indonesia, 5Immunology Master Study Program.
Postgraduate School.
Universitas Airlangga https://doi.
org/10.
22146/inajbcs.
ABSTRACT
Submitted: 2025-03-22 Accepted : 2025-10-27 Inflammatory bowel diseases (IBD.
, such as CrohnAos disease and ulcerative colitis, involve chronic inflammation of the digestive tract.
The incidence of IBD has been increasing globally, posing a growing burden despite advancements in treatment.
Novel therapies targeting adhesion molecules such as MAdCAM-1 show promise by specifically inhibiting lymphocyte infiltration into the gut, potentially offering safer and more effective treatment options.
This metaanalysis and systematic review were conducted to provide efficacy and safety analysis of ontamalimab for IBD treatment.
Dose-response (DRMA), network (NMA), and random effect meta-analysis were conducted to extract clinical response, clinical remission, biomarker change, and adverse events of Studies were retrieved from PubMed.
Cochrane, and EMBASE to describe the pooled risk ratio (RR) and heterogeneity was determined if I2 >50%.
RoB2 tool and ROBINS-I were used to assess risk of bias in RCT and clinical trial studies, respectively.
The result was considered significant if p<0.
A total of 670 studies were screened, resulting in 8 multicentre studies.
There were significant differences in clinical response (RR: 1.
95%CI: 1.
12Ae1.
p = 0.
I2= 35%), clinical remission (RR: 1.
95%CI: 1.
17Ae2.
p=0.
I2= 26%), mean change of FC (RR: 624.
95%CI: 543.
p<0.
I2= 0%), mean change of CRP serum (RR: 9.
95%CI: 7.
12Ae12.
p<0.
, and mean MAdCAM-1 serum level (RR: 235.
95%CI: 203.
80Ae267.
p <0.
between ontamalimab 75 mg and placebo after 12 wk of treatment.
Meanwhile, adverse events from both groups were similar to those observed in patients treated with either placebo or ontamalimab.
This study concluded that ontamalimab 75mg demonstrated significant efficacy in treating IBD, achieving superior outcomes in clinical response and clinical remission compared to placebo.
Importantly, no cases of PML and significant adverse events were detected, indicating a favorable safety profile relative to other anti-MAdCAM-1 therapies.
ABSTRAK
Keywords:
Ontamalimab.
Inflamatory Bowel Disease (IBD).
MAdCAM-1.
Clinical response and Meta-analisis Inflammatory bowel diseases (IBD.
, penyakit radang usus, seperti penyakit Crohn dan kolitis ulseratif, menyebabkan peradangan kronis pada saluran Insiden IBD meningkat secara global, menimbulkan beban yang semakin besar meskipun ada kemajuan dalam pengobatan.
Terapi target yang berfokus pada molekul adesi, seperti MAdCAM-1, memberi harapan baru dalam menghambat infiltrasi limfosit ke lumen usus, menawarkan pilihan pengobatan yang lebih aman dan efektif.
Tinjauan sistematis dan meta-analisis ini dilakukan untuk mengevaluasi efektivitas dan keamanan ontamalimab sebagai terapi pada IBD.
Dose-response (DRMA), network (NMA), dan metaanalisis efek random dirancang untuk menganalisa respon klinis, remisi klinis, perubahan biomarker, dan efek samping ontamalimab.
Studi diambil dari PubMed.
Cochrane, dan EMBASE untuk menjabarkan pooled risk ratio (RR) dan heterogenitas ditetapkan jika I2 >50%.
RoB2 dan ROBINS-I digunakan untuk *corresponding author: gatot_soegiarto@fk.
InaJBCS.
Volume 57.
Number 4, 2025 October: 610-622 menelaah risiko bias dari studi RCT dan uji klinis.
Hasil dinyatakan signifikan jika p<0.
Sebanyak 670 studi disaring dan diperoleh 8 studi multicenter yang memenuhi kriteria.
Terdapat perbedaan yang bermakna pada respon klinis (RR: 1,39.
95% CI: 1,12Ae1,73.
p=0,003.
IA=35%), remisi klinis (RR: 1,72.
95% CI:
1,17Ae2,53.
p=0,006.
IA=26%), perubahan rerata kadar fecal calprotectin/FC (RR:
624,29.
95%CI: 543,28Ae705,29.
p<0,001.
IA=0%), perubahan rerata kadar serum CRP (RR: 9,71.
95%CI: 7,12Ae12,31.
p<0,.
, serta kadar serum MAdCAM-1 (RR:
235,57.
95%CI: 203,80Ae267,33.
p<0,.
antara ontamalimab 75 mg dibandingkan dengan plasebo setelah 12 minggu pemberian.
Sementara itu, kejadian efek samping pada kedua kelompok serupa dengan yang ditemukan pada pasien yang mendapatkan plasebo maupun ontamalimab.
Studi ini menyimpulkan bahwa ontamalimab 75 mg menunjukkan efektivitas yang signifikan dalam penatalaksanaan IBD, dengan hasil respon klinis dan remisi klinis yang lebih baik dibandingkan plasebo.
Selain itu, tidak ditemukan kasus PML maupun efek samping berat, menunjukkan profil keamanan yang baik dibandingkan dengan terapi anti-MAdCAM-1 lainnya.
INTRODUCTION
Inflammatory (IBD) is a broad term used to describe chronic inflammation of the intestines, encompassing ulcerative colitis (UC).
CrohnAos disease (CD), and indeterminate The exact cause of IBD is not fully understood, but potential factors believed to influence its development include bacterial presence, immune system alterations, and genetic factors.
There was an almost 50% increase in IBD cases in the span of 29 yr globally, from 32 million to 4.
90 million in 2019.
This study also reports the US .
3 cases per 00 peopl.
and China .
9 cases per 00 peopl.
are the top two countries with the most cases.
2 In Southeast Asia, the average annual increase and mean annual growth in the incidence of IBD were reported as the second highest .
45% and 1.
58%, respectivel.
after East Asia, leading to significant concern in IBD healthcare.
3 The prevalence of IBD in Indonesia is approximately 0.
per 100,000 for UC and CD at 0.
33 per 1,000,000.
Despite advancements in treatment, many patients do not tolerate or respond to conventional therapies like 5-aminosalicylic acid, thiopurines.
Furthermore, the long-term use of glucocorticoids poses greater risks than benefits.
Adhesion molecules, crucial for guiding lymphocytes to inflamed gut sites, hold significant promise as treatment targets for IBD.
Mucosal addressin cell adhesion molecule-1 (MAdCAM-.
receptor, which is elevated in IBD and is responsible for lymphocyte migration into gut tissue, presents a promising new target for therapy in UC and CD.
Ontamalimab, an anti-inflammatory human immunoglobulin G2 monoclonal antibody, also known as PF-00547659, selectively binds with high affinity to MAdCAM-1, thereby inhibiting the binding of 47 lymphocytes to MAdCAM-1 receptor sites.
9 Chu et al.
,10
PF-00547659 demonstrated significantly greater efficacy than infliximab (OR=6.
95%CI 1.
09Ae37.
and azathioprine (OR=4.
95%CI 1.
93Ae9.
in inducing clinical remission.
The promising novel treatment of IBD needs to be assessed further.
Several randomized controlled trials (RCT.
have been conducted to assess the efficacy and safety of ontamalimab, including the TOSCA,11 OPERA,12 and TURANDOT13 studies, which evaluated these outcomes in both UC and CD individually.
These trials were followed by maintenance studies.
OPERA II14 and TURANDOT II,15 Setyobudi AK, et al.
Safety and efficacy of ontamalimab.
that further investigated these indicators over the long term.
Meanwhile, there are only a few systematic review or metaanalysis evaluating the efficacy and safety of ontamalimab in treating IBD.
The previous meta-analysis by Awad et ,16 included only the 25, 75, and 225 mg doses in their study.
Other doses reported in different RCTs were not examined, thereby limiting the evaluation of dose In contrast, the present DRMA meta-analysis incorporates a broader range of doses.
Moreover, it does not perform a NMA meta-analysis as conducted in the present study, that also have not been previously undertaken.
This study was conducted to complement previous studies and represents the first DRMA and meta-analysis to evaluate the efficacy and safety of ontamalimab in the management of IBD.
MATERIAL AND METHODS
Search strategy A comprehensive search was conducted using PubMed.
Cochrane, and Scopus from the earliest available date until June 19th, 2024.
The search was using keywords AuOntamalimabAy OR AuSHP647Ay OR AuMonoclonal Antibody Against Mucosal Addressin Cell Adhesion Molecule-1Ay OR AuMAdCAM-1Ay OR AuPF00547659Ay AND AuInflammatory bowel diseaseAy OR AuUlcerative colitisAy OR AuCrohn diseaseAy.
This study was registered in PROSPERO with registration number [CRD42024600.
Study selection Inclusions of the study were as follows .
Population: patients diagnosed with moderate-to-severe IBD, including CD and UC, based on American Gastroenterological Association.
Intervention: patients treated with Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-.
or ontamalimab or PF-00547659, whereas the control group was treated with placebo.
Meanwhile, interventional studies that included additional treatments alongside ontamalimab and non-English language studies were excluded to ensure consistency in data extraction and We compared various doses of ontamalimab .
and 225 m.
using the DRMA method.
Outcome: Clinical response, clinical remission, biomarker change including change in mean serum MAdCAM-1 level, mean FC concentration, mean serum CRP concentration, and adverse events.
Further information on clinical response and remission can be found in TABLE 1.
Data extraction Three review authors independently extracted data from each selected study utilizing a structured and standardized form that was created by discussion.
First authorsAo names and publication year, study design, country of origin, center of the study, grouping, sample size.
UC/CD Grade, intervention protocol, follow-up period, patientsAo mean age, clinical remission, clinical response, mean serum MAdCAM-1 level, mean FC concentration, mean serum CRP concentration, and adverse events were assesed and extracted into the form.
Quality assessment Three review authors assessed the quality of the studies independently through the risks of bias from each included study, utilizing the Cochrane risk of bias tool for five randomized trials (RoB ver.
17 and ROBINS-I for two non-randomized trials18.
The certainty of evidence was evaluated using the GRADE approach, which considers domains including risk of bias, inconsistency, indirectness, and imprecision, with the overall quality rated as AohighAo.
AomoderateAo.
AolowAo, or Aovery lowAo.
Additionally, funnel InaJBCS.
Volume 57.
Number 4, 2025 October: 610-622 plot analysis was performed to assess the potential presence of publication bias.
Any conflicts were resolved by discussion until concurrence was reached.
statistically significant heterogeneity if p<0.
05 or I2 >50%.
Statistical analysis Search results Network meta-analysis and DRMA were performed in R Studio with the AunetmetaAy and AudosresmetaAy packages.
The DRMA meta-analysis was assessed using the Greenland & Longnecker method, which estimated the outcome based on the reported effect size across multiple dose levels within each study.
19 Meanwhile, the random-effect model was expressed using Revman 5.
The pooled risk ratio (RR) with 95% CI was computed for clinical response, clinical remission, and adverse events, meanwhile mean difference (MD) with 95% CI was used to calculate the effect size for biomarker Random effect models were used to perform all meta-analysis with The systematic search identified 670 records through database searches.
Following the removal of duplicates, 570 records remained for screening.
Subsequently, 83 articles were sought for full-text retrieval after the initial screening of titles and abstracts.
Among these, 65 were excluded during the screening process due to inappropriate population .
uch as conditions other than UC or CD), unsuitable study designs, irrelevant outcomes unrelated to efficacy, biomarker changes, or adverse events, and use of interventions other than ontamalimab, as detailed in FIGURE A total of 8 studies were included in the final analysis.
RESULTS
Identification Identification of studies via databases and registers Screening Records identified from:
A PubMed .
A Cocrane .
A EMBASE .
Records removed before screening due to duplication .
Records screened .
Records excluded from title and abstract .
= .
Reports sought from retrieval .
Reports excluded A Other than IBD .
A Wrong study design .
A Irrelevant outcome .
A Wrong intervention .
Include Studies included in the systematic review .
Studies included in metaanalysis .
FIGURE 1.
PRISMA flow chart for the selected studies Setyobudi AK, et al.
Safety and efficacy of ontamalimab.
Study characteristics Eight studies were finally included in this systematic review (TABLE .
Six multicenter randomized double-blind placebo-controlled trials and two openlabel extensions assessing the long-term safety and efficacy of ontamalimab were included in this systematic review, which included a total of 957 patients.
Of these, 563 patients were treated with ontamalimab or equivalent therapies, while 394 patients were given a placebo or standard therapy as the control These studies were conducted across multiple countries, including Italy.
Spain.
Japan.
Korea, and the USA, and targeted patients with moderate-tosevere CD or UC who were refractory to conventional treatments such as corticosteroids, immunosuppressants, or anti-TNF agents.
12,14,15,20,21
The intervention protocols included ontamalimab at doses of 22.
mg every 4 wk in 5 studies.
12Ae15,20 One study incorporated a dose-escalation approach for patients with inadequate responses to the initial dose, while another study employed intravenous administration of single or multiple doses.
11,13 The follow-up periods ranged from 12 to 144 wk.
Standard therapies across the studies included corticosteroids, antiinflammatory agents, and vitamin supplements, providing a baseline for comparison with the ontamalimabtreated groups.
14,20
Clinical remission was a key outcome assessed, defined by disease-specific indices such as the Harvey-Bradshaw index (HBI) for CD and the Mayo score for UC.
For CD, clinical remission (HBI < .
was achieved in 49/115 patients .
6%) by Week 4 and 45/110 patients .
9%) by Week 8 in a phase II extension 20 Similarly, in UC, remission rates based on the Mayo score were reported as 24/153 patients .
7%) for the 25 mg dose group and 45/151 patients .
for the 75 mg dose group in a phase i RCT.
Clinical response, defined as a reduction in disease activity indices .
HBI reduction Ou3 points or a Mayo score reduction Ou3 and Ou30%), showed substantial improvements in intervention groups.
For instance, in CD, clinical response rates by Week 4 were 117/177 patients .
1%) and 93/157 patients .
2%) by Week 8 in a long-term 20 For UC, clinical response rates in an RCT were 67/111 patients .
for the 25 mg dose and 64/112 patients .
1%) for the 75 mg dose by Week 12.
Endoscopic Improvement was another critical endpoint, assessed through either centrally-read or local endoscopy scores.
In a study on UC, 32/71 patients .
1%) receiving 75 mg ontamalimab achieved significant improvement by Week 12 compared to 21/73 patients .
8%) in the placebo 13 Biomarkers such as serum CRP, fecal calprotectin (FC), and serum MAdCAM-1 levels provided additional evidence of clinical improvement.
In one study, serum CRP levels decreased from a baseline of 20.
5 mg/L .
% CI: 16.
2Ae25.
4 mg/L .
% CI: 10.
0Ae17.
by Week 12 for the 75 mg ontamalimab group.
Fecal calprotectin levels also showed reductions, with geometric mean levels decreasing from 848 AAg/g to 300 AAg/g by Week 12.
Safety profiles were evaluated across all studies.
Treatment-emergent adverse events (TEAE.
were reported in 249/268 patients .
9%) in one long-term study, with 10/268 patients .
7%) experiencing serious adverse events (SAE.
related to the therapy.
Discontinuation due to adverse events was relatively low, with rates of 15/268 patients .
6%) in the treatment period and 0/194 patients in the follow-up period.
15,20
InaJBCS.
Volume 57.
Number 4, 2025 October: 610-622 TABLE 1.
Study characteristic of publication included Follow Onta 75mg:
24 wk 5 .
HBI score of Decrease of Ou3 in HBI score from the baseline value Moderate to severe UC .
or CD .
Induction study UC Placebo:
76 Onta 25mg:
153 Onta 75mg: 151 12 wk Placebo: 38.
Onta 25mg: 39.
Onta 75mg: 41.
Moderate to severe UC .
or CD .
Induction study UC Placebo:
56 Onta 25mg:
111 Onta 75mg: 112 12 wk Placebo: 41.
Onta 25mg: 43.
Onta 75mg: 43.
SF subscore of 0 or 1 with at least a 1-point change from baseline.
RB of 0, and subscore of 0 or 1 reported by patients using daily e-diary and centrally read Decrease from baseline Ou2 points and Ou30% change, with decrease in the subscore for RB Ou1 point or a subscore for RB O1 without rescue therapy and or Decrease from baseline of MCS Ou3 with Ou30% change, accompanied by Ou1 point decrease or absolute score of O1 in RB subscore Population DAoHaens et Phase 2 Moderate to severe Vermeire et al.
Parallel
Author
Effect Measure Total patients assigned to Study Intervention Mean age (SD) Clinical Clinical response Saruta et
RCT
Moderate to severe Placebo: 63 Onta 22,5mg:
66 Onta 75mg:65 Onta 225mg: 68 12 wk Placebo: 34.
Onta 22,5mg: 37.
Onta 75mg:
Onta 225mg: 35.
CDAI score < Sandborn et al.
RCT
Moderate to severe Placebo: 63 Onta 22.
66 Onta 75mg:65 Onta 225mg: 68 12 wk Placebo: 34.
Onta 22,5mg: 37.
Onta 75mg:
Onta 225mg: 35.
CDAI <150
Decrease from baseline in CDAI Ou100 Vermeire et al.
RCT
Moderate to severe Placebo: 73 Onta 7.
71 Onta 22,5mg: 72 Onta 75mg: 71 Onta 225mg:
12 wk Placebo: 38.
Onta 5:41.
Onta 22.
Onta 75:37.
Onta 225: 41.
Mayo score
O2 with no >1 and RB
subscore O1
Decrease from baseline of MCS Ou3
with Ou30% change, accompanied by Ou1
point decrease or absolute score of O1
in RB subscore DAoHaens et
RCT
Moderate to severe Cohort 1 .
Onta 225mg:
12 wk 9 .
HBI score < 5 Cohort 2 .
Onta 225mg:
12 wk 4 .
Reduction in HBI
score from baseline by Ou 3 points Decrease from baseline of Ou3
points with Ou30% change in total MCS, accompanied by a Ou1-point decrease in RB subscore or an absolute RB subscore of O1
Reinisch, et
Open label
Moderate to severe Open Label-1
Onta 75 mg no 70 Onta 75mg
escalated to 225mg= 94
Onta 225 mg
= 166
72 wk Onta 75: 40.
Onta 225:
Mayo score O2 with no subscore >1 and a RB subscore of O1 Vermeire et al.
RCT
Moderate to severe single dose phase and multiple dose Ontamalimab:
60 Placebo: 20
4 & 12
Onta: 45.
Placebo: 47.
Mayo score O2 points with no individual Decrease from baseline in the CDAI score Ou 70 points Decrease from baseline of Ou3 points with Ou30% change in total MCS, accompanied by a Ou1-point decrease in RB subscore or an absolute RB subscore of O1 Onta: Ontamalimab.
RCT: randomized controlled trial.
UC: ulcerative colitis.
CD: ChronAos disease.
HBI: Harvey-Bradshaw index.
CDAI: ChronAos disease activity index.
RB: rectal bleeding.
MCS: Mayo clinical score Setyobudi AK, et al.
Safety and efficacy of ontamalimab.
Risk of bias domains Study Overall Vermeire21 Saruta12 Sandborn13 Vermeire13 D'Haens22 Judgement:
: Low : Some concerns Domains:
D1.
Bias arising from the randomisation process.
D2: Bias due to derivations from intended intervention.
D3: Bias due to missing outcome data.
D4: Bias in measurement of the outcome.
D5: Bias in selection of the reported result Risk of bias domains Study Overall D'Haens20 Reinisch15 Judgement:
: Low : Moderate Domains:
D1.
Bias due to confounding.
D2: Bias due to selection of participants.
D3: Bias in classification of interventions.
D4:
Bias in due to deviations from intended interventions.
D5: Bias due to missing data.
D6: Bias in measurement of outcomes.
D7: Bias in selection of the reportes result FIGURE 2.
Risk of bias assessment.
A) RoB tools for RCT, and B) ROBINS-I for non-randomized trials.
InaJBCS.
Volume 57.
Number 4, 2025 October: 610-622 Risk of bias assessment Cochrane risk of bias tool (RoB ver.
and ROBINS-I were used to assess the risk of bias in five randomized trials and two non-randomized trials (FIGURE 2A and B).
DAoHaens et al.
22 showed some concerns in two domains, resulting in moderate risk, following Reinisch et 15 with four moderate risk domains.
Summary findings table for the GRADE approach can be found in supplementary TABLE 1.
Efficacy outcomes Five studies consisting of 3 moderate-to-severe CD and 2 moderateto-severe UC were assessed.
12-14,21 The result showed that ontamalimab 75mg significantly increased clinical response (RR: 1.
95% CI: 1.
12Ae1.
p = 0.
I2=
35%) and clinical remission (RR: 1.
95%CI: 1.
17Ae2.
p=0.
I2= 26%) in comparison to placebo (FIGURE 3A and 3B).
Other than that, in comparison to placebo, ontamalimab 75mg both showed the highest OR in clinical response and clinical remission among other doses (OR 2.
95% CI 1.
OR 2.
95% CI 1.
85, respectivel.
(FIGURE 4A and 4B).
The NMA compared clinical response and clinical remission among 5 doses of ontamalimab .
and 225 m.
and placebo (FIGURE 6A and 6B).
Both clinical response and clinical remission outcomes included 29 pairwise comparisons across 6 Funnel plot analysis revealed no apparent asymmetry, suggesting a low risk of publication bias influencing the overall findings (FIGURE 5A and B).
This result indicates ontamalimab 75mg as the most reliable therapeutic benefit both in clinical response and clinical remission compared to placebo, while other doses showed less consistent effect.
FIGURE 3.
Meta-analysis of Ontamalimab 75mg in comparesion to placebo (A) Clinical Response (B) Clincal remission Setyobudi AK, et al.
Safety and efficacy of ontamalimab.
FIGURE 4.
Dose Response Meta-analysis of five doses of Ontamalimab (A) Clinical response (B) Clinical remission FIGURE 5.
Funnel plot of (A) clinical response and (B) clinical remission .
Ontamalimab 7.
5 mg b: Ontamalimab 22.
5mg c: Ontamalimab d: Ontamalimab 75mg.
e: Ontamalimab 225m.
InaJBCS.
Volume 57.
Number 4, 2025 October: 610-622 FIGURE 6.
Network meta-analysis of 5 doses of ontamalimab and placebo were assessed.
Line thickness indicates the number of (A).
Clinical response (B).
Clinical remission Biomarker change MadCAM-1 ontamalimab 75 mg and placebo were significantly different after 12 wk of treatment.
Two trials reported much lower levels of MadCAM-1 were demonstrated in ontamalimab 75 mg treatment (RR: 235.
95% CI: 203.
80Ae I2: 60%.
p <0.
compared to placebo after 12 week of treatment
(FIGURE
8A).
Significantly heterogeneity was reported from 3 trials in mean change of FC (RR: 624.
95% CI:
28Ai705.
I2: 0%.
p<0.
(FIGURE
8B) and mean CRP levels between placebo and ontamalimab 75 mg after 12 week (RR: 3.
95% CI: 0.
19Ae6.
I2:
p=0.
(FIGURE 8D).
13,21 Meanwhile change of CRP serum level (RR: 9.
95% CI: 7.
12Ae12.
I2: 90%.
p<0.
FIGURE 8C between ontamalimab 75mg and placebo was significant after 12 wk of treatment despite substantial This result supports the role of ontamalimab 75mg as targeted treatment to reduce MAdCAM-1 level.
CRP, and FC levels in comparison to Adverse events No significant adverse events (AE.
were found when compared to placebo based on a meta-analysis conducted on the AE of ontamalimab at doses of 22.
5-25 mg, 75 mg, and 225 mg, with RR 1.
% CI 0.
% CI 0.
, and 0.
CI 0.
FIGURE 9
This indicates that across various doses, ontamalimab did not show significant differences in side effects compared to the placebo, as reflected by the RR and 95%CI.
With similar results, serious adverse events seen in the ontamalimab group at the doses of 22.
5-25 mg, 75 mg, and 225 mg showed non-significant results compared to the placebo, with RR 1.
% CI 0.
RR 1.
CI 0.
RR 1.
% CI 0.
respectively (FIGURE .
Setyobudi AK, et al.
Safety and efficacy of ontamalimab.
FIGURE 7.
Comparison of serious AEs between 22.
5-25 mg, 75 mg, and 225 mg ontamalimab vs placebo InaJBCS.
Volume 57.
Number 4, 2025 October: 610-622 FIGURE 8 (A) Comparison of Mean CRP levels Between Placebo vs Ontamalimab 75 mg (B) Comparison of change FC levels Between Placebo vs Ontamalimab 75 mg (C) Comparison of change CRP levels Between Placebo vs Ontamalimab 75 mg (D) Comparison of Mean CRP levels Between Placebo vs Ontamalimab 75 mg FIGURE 9.
Comparison of Adverse Effect Between 22.
25 -25 mg Ontamalimab vs Placebo Setyobudi AK, et al.
Safety and efficacy of ontamalimab.
DISCUSSION
The study found that ontamalimab 75mg provides significantly greater clinical response and clinical remission amongst other doses in comparison to placebo to treat both UC and CD.
This result aligns with a previous study that ontamalimab 25mg does not significantly increase outcomes.
16 Studies suggest that improvements in both response and remission are more closely associated with the duration of therapy rather than with increasing doses, as higher doses may lead to excessive depletion of regulatory T cells, potentially diminishing the therapeutic effect.
13,20 In addition, the placebo effect could be explained by the carryover effect of previous anti-TNF treatment and high inflammation levels at baseline, giving better response and remission than low inflammation levels.
CRP and FC levels described systemic and local gastrointestinal inflammation.
Significant diminished level of CRP and FC after 12 wk of ontamalimab 75 mg treatment, as well as signicantly lower CRP levels in ontamalimab 75 mg compared to placebo, was described as decreased inflammation that leads Nevertheless, ontamalimab 225 mg has reversely more inflammation effects compared to ontamalimab 75 mg, which were demonstrated by higher FC levels.
This could lead to more active disease and refractory treatment of the patients.
Ontamalimab 75 mg was conclusively superior to ontamalimab 225 mg.
14,20
Moreover.
MadCAM-1 levels wes studied as one of the specific markers of IBD, and it was significantly lower in patients with ontamalimab treatment compared to placebo in this meta-analysis.
This demonstrated that ontamalimab 75 mg could be efficient in treating IBD.
Ontamalimab was found to be safe and well-tolerated across all studies at all 3 dosage levels.
These findings are consistent in the induction studies, including the TOSCA.
TURANDOT, and a new phase 3 induction study by the same author of the TURANDOT study, which were analyzed in the forest plot above but showed no statistically significant The drug also showed a good safety profile in the maintenance studies, such as OPERA II .
ncompassing both OPERA and TOSCA studie.
and TURANDOT II.
The most common AEs were linked to the underlying disease, with the worsening of UC being one of the primary concerns, along with arthralgia and upper respiratory tract Adverse events that led to treatment discontinuation were typically related to the underlying condition itself.
It is also notable to know that no cases of progressive (PML) were observed in either the induction or maintenance studies, likely attributable to its selectivity, in contrast to natalizumab, a non-selective anti-4 integrin antibody used in IBD that can affect the central nervous system and bone marrow, thereby increasing the risk of PML.
23 Most serious AEs were attributed to CD and were deemed unlikely to be related to the study drug.
Withdrawals due to AEs were primarily due to complications of CD.
This study has several limitations, including a small number of included trials and limited sample sizes.
Most of the studies had short durations, typically under 12 wk, as maintenance studies were not included.
Additionally, the analysis primarily compares ontamalimab with placebo, limiting the ability to directly assess its efficacy and safety relative to other active treatments for IBD.
Future research with larger sample sizes, longer head-to-head periods, and active comparator arms is needed to better ontamalimabAos Although the meta-analysis revealed no statistically significant heterogeneity in efficacy or adverse outcome measures, this may be due to InaJBCS.
Volume 57.
Number 4, 2025 October: 610-622 the small number of included studies and the similarity in their characteristics.
addressed potential biases by ensuring homogeneity through careful review of study features, applying a fixed-effect model, and assessing evidence quality using the GRADE approach.
The GRADE approach findings indicate moderate certainty of evidence for efficacy and safety outcomes, but low certainty for biomarker changes, primarily due to considerable heterogeneity and wide confidence intervals.
CONCLUSION
Ontamalimab, administered at a dose of 75 mg, demonstrated efficacy in the management of IBD, as evidenced by its superior clinical response rates and clinical remission outcomes when compared to placebo.
Moreover, no significant AEs were observed during the study period, highlighting its favorable safety profile relative to other antiMAdCAM-1 therapies.
These findings underscore the potential of ontamalimab as an effective and safe therapeutic option for IBD.
Nevertheless, while ontamalimab 75 mg shows promising efficacy and safety, longer-term headto-head other biologics and other established treatments are warranted to confirm its clinical utility.
ACKNOWLEDGMENTS
The authors would like to convey their sincere gratitude to mentors and colleagues who helped them during the process of developing this meta-analysis and systematic review.
REFERENCES