296
The first evaluation of alicaforsen in UC, a randomised double-blind placebo-
controlled escalating dose trial of 40 patients with mild-moderately active UC,
evaluated the efficacy and safety of alicaforsen enemas administered in four dif-
ferent doses [ 77 ]. Alicaforsen enemas resulted in a dose-dependent improve-
ment in DAI (overall P = 0.003). The drug was well tolerated with no major
safety issues.
The local and systemic availability of alicaforsen enema, as also its activity when
administered once daily, was assessed in UC patients in an open-label study of 15
subjects who received nightly enemas of alicaforsen (240 mg) over 6 weeks [ 78 ]. A
46% reduction in mean DAI and a 33% rate of remission as defined by complete
mucosal healing were observed at the end of treatment. In an open-label trial in 12
patients with chronic, unremitting pouchitis, treated with 240 mg alicaforsen anti-
sense enema nightly for 6 weeks, alicaforsen appeared to improve the PDAI score,
clinical symptoms and endoscopic mucosal appearance [ 79 ]. In a recent case series,
alicaforsen enemas significantly reduced clinical and endoscopic disease 2–3 months
after therapy [ 80 ]. The enema formulation is currently being evaluated in a phase III
study for chronic antibiotic refractory pouchitis (http://www.clinicaltrials.gov:
NCT02525523). Taken together, alicaforsen has shown conflicting data for CD
patients but more promising data for UC. The relative lack of efficacy may be due
to the non-dominant role of ICAM-1 expression in the inflammatory response in
IBD [ 81 ].
Conclusion
Anti-adhesion therapies are a welcome addition to the expanding armamentarium of
IBD treatment with gut specificity of newer agents being particularly appealing.
The potential for predictive biomarkers has exciting implications for further research
and holds promise for personalised medicine. Future studies will provide further
insights from real-world data on remission and impact on mucosal healing, hospi-
talisation and surgery. Data in specific patient populations (e.g. pregnancy, extremes
of age, prevention of postoperative recurrence and malignancy) are much needed.
Meanwhile, evolving understanding of the complex immuno-inflammatory path-
ways has already seen the development of a plethora of agents with several others
in the pipeline. Targeting adhesion molecules appears to represent a fitting piece in
the daunting puzzle of the aetiopathogenesis of IBD. The prospect of further intel-
lectual effort invested in this mechanism being rewarded through clinically mean-
ingful outcomes for our patients is now realistic.
Disclosures Francis A. Farraye, MD, MSc: Advisory Board: Abbvie, Janssen, Merck, Pfizer,
Takeda, Consultant: Braintree, Grant Support: Prometheus, Takeda, Stock Holder:
Cellceutix
Jimmy K. Limdi MBBS FRCP: Advisory Board: Abbvie, MSD, Falk pharma
Educational Grants Abbvie, MSD, Dr. Falk Pharma, Tillotts, Ferring
J.K. Limdi and F.A. Farraye