Source: Orthopedics  |  Posted 8 years ago

Daily enemas combining epidermal growth factor (EGF) and oral mesalamine may reduce disease activity and induce clinical remission in patients with left-sided ulcerative colitis or proctitis.

"EGF as an enema has the advantage of delivering the peptide to the injured area in a readily available, intact, active form," notes Atul Sinha, MRCP, Leicester Royal Infirmary, United Kingdom.

Dr. Sinha and colleagues randomised 24 patients with mild-to-moderate left-sided ulcerative colitis to daily self-administered EGF enemas or placebo for 2 weeks. Ulcerative colitis was indicated by a score of at least 5 on the St. Marks index, although most severe disease equals 12.

The active enemas contained 5 mcg EGF in 100 mL of a gelatin carrier solution, while the placebo enemas contained solution alone. At randomisation, all patients either started 1.2 mg/day oral mesalamine or increased their mesalamine dosages by 1.2 mg/day.

After 2 weeks of treatment, 83% of the 12 patients receiving EGF and 8% of 12 using placebo were in remission (St. Marks score of 4 or less). The patients using the EGF enemas reported no side effects.

At 4 weeks, 83% of patients treated with EGF and 25% of placebo patients were in remission according to the St. Marks score. Among those with active disease, mesalamine therapy was increased or changed based on clinical need, while patients in remission either discontinued mesalamine or returned to their pretrial regimen.

The 8 EGF patients in histologic remission at 4 weeks, compared with 1 placebo patient, remained in remission at 12 weeks post-treatment. No sigmoidoscopy was performed at 12 weeks, so the St. Marks score could not be assessed.

A retrospective review at 6 months revealed that 6 (50%) of the EGF and the entire placebo-treated group required local or systemic corticosteroid treatment for their disease.

The researchers conclude, "This study provides preliminary data suggesting that EGF enemas are an effective treatment for active left-sided ulcerative colitis."

In a corresponding editorial, Richard J. Farrell, MD, of Beth Deaconess Medical Center, Boston, Massachusetts, United States, suggests that its small patient population and use of an invalidated activity scale as the primary end point limit the value of this study. Dr. Farrell notes that this "prevents comparison with the results of larger studies of patients with active distal ulcerative colitis, which typically use validated indexes such as the Mayo Index to define remission." He also noted that the concomitant use of oral mesalamine makes the benefits of EGF difficult to determine.

Dr. Farrell cautions that this study's use of EGF in concentrations 100 times as high as those normally found in gastric juice could induce malignant cell transformation in the regenerating mucosal epithelium. Longer follow-up than that of this study is needed, Dr. Farrell writes.

This trial does suggest preliminary support for a specific growth factor, perhaps as adjuvant therapy, for active distal ulcerative colitis. Dr. Farrell writes, "The carcinogenic potential of EGF therapy should be weighed against increasing evidence that regular use of mesalamine may reduce the risk of colorectal cancer in patients with inflammatory bowel disease."