The advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD in the last 15 years, but primarily and more importantly secondary loss of response is often observed. Fortunately , new treatment options have been actively explored and some have already entered our clinical practice. In the class of anti-
cytokine agents, the anti-
IL12/IL23
monoclonal antibodies (mAbs) have entered clinical practice with the anti-p40 mAb
ustekinumab in
Crohn's disease (CD). Also, more selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting
IL-17 downstream which have failed in clinical trials despite their clear efficacy in
psoriasis (Verstockt et al. in Expert Opin Biol Ther 17(1):31-47, 2017; Verstockt et al. in Expert Opin
Drug Saf 16(7):809-821, 2017). Following up on the efficacy of the anti-adhesion molecule
vedolizumab,
etrolizumab (anti-beta-7 integrin) and
PF-00547659, an anti-MadCam mAb, are being developed (Lobaton et al. in Aliment Pharmacol Ther 39(6):579-594, 2014). Oral anti-trafficking agents, such as
ozanimod, targeting the
S1P receptor responsible for the efflux of T-cells from the lymph nodes, have also shown efficacy in patients with
ulcerative colitis (UC) (Sandborn et al. in N Engl J Med 374(18):1754-1762, 2016). Oral agents inhibiting cell signaling have been explored successfully in IBD.
Tofacitinib, a non-selective oral
Janus kinase (
JAK) inhibitor, is effective in patients with UC and several other more or less selective Jak1, 2 and 3 inhibitors are being developed for the treatment of CD and UC (Sandborn et al. in N Engl J Med 376(18):1723-1736, 2017; Vermeire et al. in Lancet 389(10066):266-275, 2017; De Vries et al. in J Crohns
Colitis 11(7):885-93, 2017). Finally, despite initial disappointing results with systemic administration of mesenchymal stem cells, Alofisel, adipose tissue derived, allogeneic mesenchymal stem cells, locally injected in perianal
fistula tracts, induce long-lasting beneficial effects and the
drug has been approved in Europe (Panes et al. in Gastroenterology, 2017). In summary, the quest for new treatment options in IBD is very active and justified by the high medical need and unresolved problems patients are facing.