Tumor necrosis factor (TNF) alpha inhibitors, in particular, IFX, have been evaluated in the maintenance of remission in UC. Current guidelines recommend that biologic agents are used only in patients failing conventional therapies or who are steroid dependent. Infliximab in moderate-to-severe ulcerative colitis.  IFX is a TNF-alpha inhibitor with steroid-sparing effect in UC and may be given every 8 weeks for scheduled maintenance after the initial loading buy Y-27632 dose. Two large randomized placebo-controlled trials of IFX (ACT 1 and ACT 2) enrolled moderate to severe UC patients unresponsive to standard therapy.158 The studies showed that the clinical

response rates in patients treated with IFX given at weeks 0, 2, and 6 and then every 8 weeks through week 46, was significantly higher (46%) than for placebo at week 54 (20%) (P = 0.001). Similarly, the 54-week remission rate was significantly higher for the

groups treated with IFX at 35% compared to placebo remission rate of selleck 17% (P = 0.001). Further analysis of the ACT 1 & 2 trial data indicates that there was an associated reduction in colectomy (hazard ratio 0.57, 95% CI 0.37–0.89) during the trial. However, even at 5 mg/kg IFX every 8 weeks, only 21% (at 7 months) and 26% (at 12 months) achieved steroid-free remission.30 Adverse effects to anti-TNF-alpha agents.  Adverse events reported with IFX therapy include increased susceptibility to infections that might be primary, opportunistic or reactivation, infusion-related reactions, serum sickness-like reaction, neurological, immunological and other reactions. IFX is contraindicated in people with moderate or severe heart failure, active infections, and demyelinating conditions. Anti-TNF drugs increase the risk of reactivation of latent TB and

can result in overwhelming Janus kinase (JAK) disseminated and extra-pulmonary disease by 4–20 fold.159 Other biologic agents.  Adalimumab may be an option in the maintenance of clinical remission of UC patients intolerant to, or with lost efficacy to, IFX.160 Large scale studies are currently underway in the evaluation of this and other biologic agents in UC. Methotrexate.  Data on methotrexate (MTX) in the treatment of UC remain limited and inconsistent. A randomized placebo-controlled study using MTX at the dose of 12.5 mg/week orally showed no benefit.161 Higher dosage and parenteral administration, however, may be beneficial. Open labeled studies have achieved remission rates of 42–60% including in patients who had failed AZA/6-MP.162,163 Adequately-powered prospective randomized controlled studies of MTX in UC are required. Methotrexate remains a therapeutic option in refractory UC patients who failed AZA/ 6-MP treatment given the limited availability of alternatives to thiopurines, such as biologic agents, in many parts of Asia. Calcineurin inhibitors.  Cyclosporin and tacrolimus are calcineurin inhibitors that reduce interleukin-2 production. Cyclosporin.