The clinical implications of thalidomide in inflammatory bowel diseases

Abstract

Thalidomide has anti-inflammatory and anti-angiogenetic activity that makes it suitable for treating inflammatory bowel diseases (IBD). The recent guidelines from the European Crohn’s and Colitis Organization/European Society for Pediatric Gastroenterology Hepatology and Nutrition conclude that thalidomide cannot be recommended in refractory pediatric Crohn’s disease but that it may be considered in selected cohorts of patients who are not anti-TNFα agent responders. The main adverse effect is the potential teratogenicity that renders the long-term use of thalidomide problematic in young adults due to the strict need for contraceptive use. In short-term use it is relatively safe; the most likely adverse effect is the neuropathy, which is highly reversible in children. So far the use of thalidomide is reported in 223 adult and pediatric IBD patients (206 with Crohn’s disease). In the following sections, the authors will discuss efficacy and safety of thalidomide, in the short-term treatment of IBD.

Keywords:

• child
• Crohn’s disease
• inflammatory bowel disease
• thalidomide
• ulcerative colitis

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Thalidomide has immunomodulatory, anti-inflammatory and anti-angiogenetic activity that renders it particularly suitable in the treatment of inflammatory bowel diseases.

• At pediatric age, thalidomide has been employed in six case series and clinical remission rate ranged from 63 to 100%. Steroids tapering rate was between 50 and 100%.

• At adult age, thalidomide has been employed in seven case series and clinical remission rate ranged from 20 to 100%. Steroids tapering rate was between 43 and 100%.

• Thalidomide induces not only clinical remission but also histological and endoscopic healing.

• The maximum duration of the therapy was 79 months in children and 59 in adults.

• The adverse events involve several functions and systems (neuromuscular, psychological/psychiatric, cutaneous, digestive, cardiovascular/hematological, ocular, sexual); these are almost reversible by tapering/suspending of the drug.

• Clinical remission is generally induced by thalidomide in the first 8 weeks of treatment; therefore, the severe adverse events that determine the drug’s discontinuation after the 12th week potentially do not prevent that thalidomide exerts its clinical effects.

• Early adverse effects which required the suspension of thalidomide within the first 12 weeks occurred in 6.7% of all patients; late adverse events requiring thalidomide discontinuation after 12 weeks in 21.6%.

• Currently, a large amount of data comes from uncontrolled studies or case series; some studies, nevertheless, have good level of evidence, mainly in children. Therefore, based on the available evidences so far, we could conclude that thalidomide might be employed as a rescue therapy in very severe inflammatory bowel diseases cases refractory to conventional treatments.