Reviews/TNF Alpha Inhibitors/Infliximab and adalimumab induce remission in moderate-to-severe Crohn's disease
· TN-IBD-01 · v2
Borderline: within 4 points of the Established/Likely boundary, so a re-grade could land either side.
This corpus asks whether two anti-TNF drugs, infliximab and adalimumab, can bring moderate-to-severe Crohn's disease into remission. Several controlled trials point the same way: adalimumab beat placebo for remission at four weeks [1], infliximab produced steroid-free remission in adults [5] and clinical and endoscopic remission in newly diagnosed children [4], and a large real-world cohort recorded remission with both drugs after a year [7]. The earliest infliximab experience [14] agrees. The panel treated the direction as consistent and replicated across independent trials and cohorts. What holds it back from being cleaner is that the tidiest adult adalimumab induction trial was run only in patients who had already failed infliximab [1], the strongest adult infliximab result was measured at week 26 inside a combination-therapy trial [5], and two supporting datasets are in children [4][6].
Placebo- and comparator-controlled trials show both agents inducing remission: adalimumab 21% versus 7% at week 4 [1] and, among responders, 40% and 47% versus 17% at week 26 [3]; infliximab monotherapy 44.4% corticosteroid-free remission versus 30.0% on azathioprine [5] and, in first-line paediatric disease, 59% versus 34% clinical and 59% versus 17% endoscopic remission at week 10 [4]. The originating infliximab pilot normalised disease activity in 8 of 10 patients [14]. The PANTS cohort recorded year-1 remission of 40.2% for infliximab and 35.9% for adalimumab [7], and a matched paediatric cohort found 63% versus 59% steroid-free remission with the two drugs [6]. Direction is unanimous across RCTs and observational data. The contested point: The division is not over direction but over directness of the adult induction evidence: the cleanest adult adalimumab induction RCT [1] enrolled only infliximab-refractory or intolerant patients, and the strongest adult infliximab endpoint [5] is read at week 26, blurring induction with early maintenance. A dedicated adult de novo monotherapy induction RCT for each drug is not present, leaving adult infliximab induction partly resting on a 10-patient 1995 pilot [14].
All 17 papers behind this claim with their DOIs and what each does to it, the panel’s arbitration, the evidence gap map and the open research questions. Free, and sent to your inbox.
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The only clean placebo-controlled adult adalimumab INDUCTION RCT in the corpus (GAIN [1]) is restricted to infliximab-refractory/intolerant patients, making it indirect for de novo moderate-to-severe CD; absolute remission was modest (21%).
The strongest adult infliximab endpoint (SONIC [5]) is measured at week 26 within a combination-therapy trial, conflating induction with early maintenance rather than isolating induction.
Where it remains uncertain. The one clean adult adalimumab induction RCT is confined to an infliximab-refractory population [1] and the strongest adult infliximab endpoint is measured at week 26 [5], so neither isolates de novo monotherapy induction.
Aleatory
Even where significant, remission fractions are limited (21% at week 4 [1]; roughly a third at year 1 in [7]), so individual patient outcomes vary widely.
Epistemic
The corpus lacks a dedicated adult placebo-controlled de novo monotherapy induction trial for either drug; adult infliximab induction otherwise rests on a 10-patient pilot [14].
The load-bearing papers from a corpus of 17, each classified by what it does to the claim. Every DOI is taken from the corpus the claim was graded on.
Placebo-controlled RCT showing adalimumab induces remission in adult moderate-to-severe CD.
“Twenty-one percent (34 of 159) of patients in the adalimumab group versus 7% (12 of 166) of those in the placebo group achieved remission at week 4 (P < 0.001).”
Panel auditInternal validity: high · scope of inference: Adults with moderate-to-severe CD who had symptoms despite infliximab or were intolerant of it; 4-week induction only.Key limitations: infliximab-exposed population only · no maintenance or long-term data · no active comparator
RCT confirming adalimumab achieves remission versus placebo in moderate-to-severe CD.
“The percentage of randomized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 (40%, 47%, and 17%, respectively; P < .001)”
Panel auditInternal validity: high · scope of inference: Moderate-to-severe CD patients who first responded to open-label adalimumab induction; speaks to maintenance of remission through 56 weeks.Key limitations: maintenance endpoint, not induction · randomized population restricted to responders · induction arm uncontrolled
Induction RCT showing infliximab induces clinical and endoscopic remission in moderate-to-severe CD (paediatric).
“a higher proportion of patients in the FL-IFX group than in the conventional group achieved clinical (59% vs 34%, respectively, p=0.021) and endoscopic remission (59% vs 17%, respectively, p=0.001).”
Panel auditInternal validity: medium · scope of inference: Newly diagnosed paediatric (3-17 years) moderate-to-severe CD; comparator is conventional therapy, not placebo.Key limitations: paediatric population · open-label · comparator is active conventional therapy · week-52 remission not significant
Supports adalimumab remission in moderate-to-severe CD, with a non-significant deep-remission signal early and significant by week 52.
“Rates of deep remission were 16% in patients given adalimumab vs 10% in those given placebo (P = .34) at week 12, and 19% vs 0% (P < .001) at week 52.”
Panel auditInternal validity: medium · scope of inference: Moderate-to-severe ileocolonic CD; deep remission as a composite clinical-endoscopic endpoint, not clinical remission alone.Key limitations: exploratory analysis · composite endpoint not identical to claim's remission · week-12 result not significant
4 of 17 papers shown. The full review lists all of them, with the panel’s arbitration →
Claims are graded at each quarterly release, and re-graded between releases only when a pivotal trial lands. Every change is a new version of the claim.
Multiple independent primary RCTs demonstrate statistically significant remission induction for both agents, warranting an Established tier held conservative for residual scope and indirectness limits.
Release 2026-q4 re-graded every claim from its corpus under protocol v0.19. An earlier release's grade is shown for the record; it came from an earlier protocol and is not a movement.
Assumptions that carry weight but are not themselves established.
The panel records the gap that would most move the claim, and the study that would close it.
Adult de novo monotherapy induction RCT for each drug. The corpus has no clean adult placebo-controlled de novo monotherapy induction trial; adalimumab's cleanest adult induction RCT is refractory-only [1] and infliximab adult induction leans on a 10-patient pilot [14]. The panel rates this the highest-importance open gap for the claim, and names the study design that would close it: A double-blind, placebo-controlled induction RCT in treatment-naive adults with moderate-to-severe CD, each drug as monotherapy, with remission as the primary endpoint at an induction timepoint.
Open question: Do infliximab and adalimumab induce remission in treatment-naive adults with moderate-to-severe CD as monotherapy? Why it is still open: The clean adult adalimumab induction RCT is infliximab-refractory [1] and adult infliximab monotherapy induction rests on a 10-patient pilot [14]; no de novo adult monotherapy induction RCT is in the corpus.
Priors is a sceptical first reader, not peer review, and not medical advice.
Release 2026-q4 · graded 26 Oct 2026 · protocol v0.19