Toxicity worries with the Jak inhibitors are nothing new, but do not yet seem to have held back sales forecasts. The question is whether this will change in light of a new safety update on Pfizer’s Xeljanz. Xeljanz already has a black-box warning for thrombosis and malignancies, and yesterday a post-marketing study failed to show that the drug was non-inferior to a TNF inhibitor on rates of major adverse cardiovascular events and cancers. Will Xeljanz get pulled from the market? Probably not, reckons Bernstein’s Ronnie Gal, but it might end up being relegated to a last-ditch option. As for the other Jaks, much will depend on whether they can avoid the taint that will now be associated with Xeljanz. Currently, the class is forecast to almost catch the TNF inhibitors in 2026 in terms of sales, and the product with the most to lose is Abbvie’s Rinvoq, the analysis below shows. Abbvie told Mr Gal that it has not seen a signal for increased Mace or malignancies across its pooled Rinvoq safety data. The more selective Jak comes with a less stringent black-box warning than Xeljanz, but has not escaped toxicity concerns entirely.