Topical treatment with the Toll-like receptor agonist DIMS0150 has potential for lasting relief of symptoms in patients with chronic active ulcerative colitis by restoring glucocorticoid sensitivity.

BACKGROUND: Patients with chronic active ulcerative colitis (UC) are regarded as treatment failures and represent an area of high unmet medical need, as normally the only remaining option is colectomy. METHODS: We treated a total of eight chronic active severe UC outpatients with the immunomodulatory agent DIMS0150 as an add-on to current therapies. Seven patients received a single topical dose of 30 mg and one special case subject received three doses with 4 weeks between dosing occasions. All patients were classed as treatment failures and were elected for colectomy. Efficacy evaluation was determined in terms of colitis activity index, endoscopic improvement, and histologic disease activity assessed primarily at week 12 with a follow-up period of over 2 years. Glucocorticoid sensitivity was assayed by in vitro measurement of interleukin 6. RESULTS: All patients demonstrated a pronounced and rapid reduction in their colitis activity index within 1 week following a single intracolonic administration via colonoscope of the agent DIMS0150. Further improvements were evident at week 4, resulting in a clinical response rate for the single-dose treatment of 71%, with 43% in clinical remission. By week 12 the clinical response and remission rates had reached 82% and 71%, respectively. A follow-up period of over 2 years posttreatment indicated that all but one of the treated patients had avoided the need for colectomy, with the longest patient being in symptom-free remission for over 27 months. Treatment with DIMS0150 restored glucocorticoid sensitivity. CONCLUSIONS: DIMS0150 may have the potential to be an effective agent to treat chronic active UC patients with the prospect to avoid colectomy on a long-term basis and is currently the subject of a clinical phase III study (EudraCT number: 2011-003130-14).

Interferon-beta-1a for the treatment of steroid-refractory ulcerative colitis: a randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: We performed a randomized, double-blind, placebo-controlled, multicenter trial to investigate the efficacy and safety of recombinant interferon-beta-1a (rIFN-beta-1a) in outpatients with active steroid-refractory ulcerative colitis. METHODS: Ninety-one randomized patients subcutaneously received 3 MIU rIFN-beta-1a (group A, n = 32), 1 MIU rIFN-beta-1a (group B, n = 30), or placebo (group C, n = 29) 3 times a week over a period of 8 weeks in addition to standard therapy. An intention-to-treat analysis was performed to evaluate the efficacy and safety of treatment. RESULTS: In all 3 groups, the median prestudy clinical activity index (CAI) was 10. In 18 of 32 patients (56%) in group A, in 11 of 30 patients (36%) in group B, and in 10 of 29 patients (34%) in group C, a reduction of the CAI of 6 points or greater (response) was achieved (differences were not statistically significant). Complete response (reduction of CAI to < or =4) was achieved in 56%, 30%, and 38% of patients in groups A, B, and C, respectively. Compared with baseline, the median endoscopic index had been reduced by 5, 3, and 4 points in groups A, B, and C, respectively. Steroid reduction was 12 mg in group A, 6 mg in group B, and 10 mg in group C. Identical side effects occurred in all 3 groups. Seven serious adverse events were reported (1 in group A and 6 in group C). All were unrelated to therapy as judged by the investigating physicians. CONCLUSIONS: rIFN-beta-1a was safe but not significant, at the dosage and/or duration of treatment used, in steroid-refractory ulcerative colitis. Further studies are indicated.

Successful application of highly purified natural interferon alpha (multiferon) in a chronic hepatitis C patient resistant to preceding treatment approaches.

A currently 65-year-old patient with histologically proven chronic hepatitis C and chronic hepatitis B (seroconversion in 1990) and additional compensated cirrhosis of the liver (Child A) achieved sustained complete biochemical and viral response following 5 and 14 months respectively of therapy with highly purified natural leukocyte interferon-alpha (3 x 3 MU weekly, nIFN-alpha, Multiferon). Prior to this treatment, various other therapy approaches including recombinant interferon-alpha2b (rIFN-alpha2b) or a combination of natural interferon-beta (nIFN-beta) and interferon-gamma (rIFN-gamma) had been carried out. Unfortunately, these had been unsuccessful. After a total treatment period of 76 months with nIFN-alpha and a subsequent follow-up period of 30 months, no relapse of chronic hepatitis C occurred. The patient's tolerance of the treatment was excellent and no substantial drug-related adverse events were observed. nIFN-alpha, which - unlike the recombinant IFN-alpha2 preparations - is a mixture of various physiologically expressed IFN-alpha subtypes, could possibly be an alternative in the treatment of difficult-to-treat patients with chronic hepatitis C.

Successful long-term application of highly purified natural interferon-alpha (multiferon) after preceding interferon approaches in a chronic hepatitis C patient with thrombocytopenia.

Treatment approaches with recombinant IFN-alpha2b and natural IFN-beta in a patient with chronic hepatitis C (genotype 1b) and cirrhosis had, in both cases, to be terminated prematurely due to breakthrough phenomena and thrombo-leukocytopenia up to WHO grade 3. After the patient was switched to highly purified natural IFN-alpha (Multiferon) the thrombocyte and leukocyte counts increased significantly, and sustained complete biochemical and virological response could be achieved.