A century of IBD drugs. Part 1: the people behind the discoveries. It starts with a post-mortem. London, 1859. Samuel Wilks calls it ulcerative colitis. It was probably Crohn's. Then half a century of a handful of drugs. Sulfasalazine. Steroids. 5-ASA. Thiopurines. Ciclosporin. The first randomised trial in IBD? Cortisone v placebo, Oxford, 1955. Then 1993. Sander van Deventer and his team in Amsterdam give Jan Vilček's anti-TNF antibody in Crohn's for the first time. Infliximab. Everything changes. After that, gut-only vedolizumab, IL-23, JAK inhibitors. But this is really about the people. • Nanna Svartz, Sweden's first woman professor of medicine, designed sulfasalazine. • Gertrude Elion made 6-mercaptopurine and won a Nobel Prize. • Azad Khan, from Bangladesh, showed which half of sulfasalazine actually works. • Andrew Lazarovits made the antibody that became vedolizumab and died at 43, long before it was licensed. • Brian Feagan gave the very first dose of vedolizumab, in London, Ontario, and led the trials from phase 2 to GEMINI 1. He died last November. • Stephan Targan led the first big infliximab trial, then tied TL1A to gut inflammation. We should not forget them. Who did I miss? Part 2 soon: the trials that taught us how to use them.

The next new drug in ulcerative colitis may well be one you haven’t heard of. Obefazimod. A once-daily pill, first in its class, and it works in a way none of our current drugs do. It doesn’t block a cytokine or a receptor. It binds the cap-binding complex in the nucleus and strengthens the splicing of one long non-coding RNA, which releases more miR-124. That microRNA is a brake immune cells already have. Turn it up and the inflammatory signals fall, several at once, from inside the cell. If it’s coming to clinic, we’d best understand how it works. So I made this, step by step. The numbers so far. At week 8, pooling both ABTECT induction trials, 21% were in clinical remission on 50 mg against 4% on placebo. At week 44, among those who had responded, it was 51% against 10% (from the June press release). Abivax plans to file in the US late this year. The full maintenance data are presented at UEG next Monday, 19 October, at 10:50.