New Drugs on the Horizon for IBD

Abstract

TNF antagonists have revolutionized the treatment of IBD. Nevertheless, between 30 and 45% of patients discontinue infliximab and other TNF antagonists over a 2- to 6-year period due to nonresponse, loss of response, or adverse events. Accordingly, the need for novel therapies grows each year. Recent studies have demonstrated the promise of new drugs with distinct modes of action for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). These include agents targeting leukocyte trafficking, therapies directed against IL-12/23 and Janus kinases (JAK), and antibodies against the classic inflammatory cytokine, IL-6. The anti-α₄-integrin antibody, natalizumab, was the first effective antitrafficking agent for CD; however, its use has been greatly limited by the risk of progressive multifocal leukoencephalopathy. Therefore, second-generation antitrafficking agents have focused on restricting leukocyte blockade to the intestine through mechanisms interfering with α₄β₇-integrin and its interaction with mucosal addressin cellular adhesion molecule 1. IL-23 is a cytokine central to the adaptive immune responses that characterize IBD. Ustekinumab, targeting the p40 subunit of IL-12 and IL-23, and the oral JAK inhibitor tofacitinib have proven to be effective in phase 2 trials in CD and UC, respectively. In addition, antibodies targeting the proinflammatory cytokine IL-6 are being studied in CD. Each of the approaches described have promise as well as limitations, so it is likely that the search for novel agents in IBD will continue.

Recent trends and future directions for the medical treatment of ulcerative colitis

“…The adverse effects were comparable between the vedolizumab group and placebo group in most studies. No cases of progressive multifocal leukoencephalopathy have been reported in previous studies [50][51][52][53][54].…”

“…For long-term efficacy, 41.8-44.8 % of patients who continued to receive vedolizumab every 8 weeks or every 4 weeks were in clinical remission at week 52, whereas only 15.9 % of patients who switched to placebo were in clinical remission at week 52 [50]. In the GEMINI I study, 44 % of patients had previously received an anti-TNF treatment, and this high percentage suggested that a highly refractory group of patients were included in this study [51]. However, the odds ratio for the clinical response of vedolizumab in compared to placebo was comparable between patients with prior anti-TNF treatment and patients without prior anti-TNF treatment.…”

Crosstalk between the gut and the liver via susceptibility loci: Novel advances in inflammatory bowel disease and autoimmune liver disease

“…Patients with greater active UC levels treated with oral JAK inhibitor Tofacitinib have a higher effective and remission rate than those receiving the placebo [70]. Moreover, with the theoretical basis, PSC as an untypical autoimmune disease, may benefit from the treatment of Tofacitinib.…”

Autoimmune Diseases of Digestive System

“…Обнадеживающие результаты были получены в исследо-ваниях по изучению эффективности и безопасности пре-паратов, влияющих на миграцию лейкоцитов, антагони-стов интерлейкина 12, интерлейкина 23 и янус-киназы, а также антител к интерлейкину 6. Каждый из перечислен-ных выше препаратов обладает как рядом преимуществ, так и рядом ограничений к применению, в связи с чем требуются дальнейшие исследования в этой области [48]. Кроме того, возможность применения у пациентов с ВЗК таких препаратов, как пробиотики, молекулы, восстанав-ливающие экспрессию белков, формирующих плотные контакты или их синтетические аналоги, синтетические аналоги антимикробных пептидов, и соединения, обе-спечивающие дифференцировку макрофагов в заданном направлении, также подлежит обсуждению [40].…”