First thoughts on VERDICT ... pending publication of the full manuscript by @vipuljairath and colleagues. 672 pts with mod-sev UC randomised to 1 of 3 targets on a vedo-based algorithm (stepped up to q4w if needed), with central reading of endoscopy and histology: • G1: symptoms • G2: + endoscopic remission (MES 0–1) • G3: + histological remission (Geboes <2B.0) The primary outcome was time to a UC complication over up to 80 weeks from reaching the target. Mean age was 41, with eight years of disease, a Mayo score of 8.7, nearly two-thirds Mayo 3, almost half on steroids and a fifth after an advanced therapy. By week 48, 74% (G1), 56% (G2) and 52% (G3) had reached their targets. Treating to endoscopy made a huge difference: 22% of G1 had a UC complication, against 7% in G2 and 9% in G3. The primary comparison, histology (G3) against symptoms (G1), gave a hazard ratio of 0.33 (95% CI 0.17 to 0.67), and endoscopy against symptoms (G2 vs G1) gave 0.30 (0.14 to 0.64). In the Q&A, Vip said the effect was greater still at Mayo 0 (data not shown). About half the complications were rescue therapy for a flare; only one was an admission and none a colectomy. We don't know what happened to the patients who did not meet their targets, across all groups. But there was no clear additive benefit from histology: G3 vs G2 had a HR of 1.10 (0.45 to 2.69). Read that with one more number. 79% of group 2 (99 of 125) were also in histological remission when they reached their endoscopic target, so the groups were clinically similar and the comparison rested on about one in five. And endoscopy was read centrally. When it is, Mayo 0 is usually free of neutrophils: 84% in LUCENT and over 90% in QUASAR. Local reading is another matter. In OCTAVE, central readers confirmed only 38 to 46% of local Mayo 0 calls. We do not have the equivalent data on paired centrally read endoscopy plus histology in UC patients not on advanced therapy (as far as I know) - that might matter in the real world. We know histological inflammation carries long-term risk, including cancer. VERDICT covers only one to two years. Most of that long-term evidence comes from scoring old H&E slides, recut from paraffin blocks if needed. You can't go back and re-read an old endoscopy the same way. So ... with endoscopy read well, histology added nothing we could detect. In the clinic, where we read our own scopes, it may still catch what endoscopy misses. FINALLY ... in the debate on histology vs endoscopy we must not lose sight of just how important VERDICT is for treat-to-target in UC. It is very clear that treating to endoscopic healing makes a huge difference to important patient outcomes. Of course, I still want to know if calprotectin is a good enough proxy for the real world ... ok let's await the full paper!

Following on from yesterday's post on biosimilars, here's the updated IBD drug timeline. It shows what we have, what's coming, and when each drug goes biosimilar or generic. Three things stand out. 1. the biosimilar wave is speeding up. IFX biosimilar in 2013. ADA in 2017. USTE in 2024. TOFA generics approved in the UK this year. Biosimilar VEDO is already under review at the EMA, so 2027 looks likely. GUS around 2031. RISA and UPA around 2033. 2. within a decade, almost everything we use today will be biosimilar or generic. 3. the new drugs keep coming. Obefazimod, a first-in-class oral drug for UC. Three anti-TL1A antibodies: tulisokibart, afimkibart and duvakitug; with more to follow Icotrokinra, an oral peptide that blocks the IL-23 receptor. More options than ever, and most of today's drugs at a fraction of today's prices. That means: p19s top-down. Combination therapy upfront. Advanced therapy for everyone who needs it, when they need it. The question is no longer whether we can afford to treat early and effectively. It's whether our services can deliver it. IMPLEMENTATION. Again. (Dates are EMA/MHRA. The future ones are my best estimates.)