title: An open-label pilot trial of cladibrine (2-cholordeoxyadenosine) in patients with primary sclerosing cholangitis.
abstract: Cladribine (2-chlorodeoxyadenosine) is a nucleoside analog with specific antilymphocytic activity that has been used in patients with a variety of lymphoid malignancies and autoimmune diseases. Primary sclerosing cholangitis (PSC) is a chronic hepatic autoimmune disorder of unknown etiology, thought to be mediated by biliary autoreactive cytotoxic lymphocytes. Because cladribine is an effective antilymphocytic drug, it may have potential disease-modifying activity in patients with PSC. We studied four patients with stages I and II PSC in an open-label pilot trial of 6 months' duration and 2 years' follow-up. Drugs were administered at 0.1 mg/kg/d subcutaneously for 5 days per monthly cycle for a total of 3 cycles. Patients evaluation included monthly liver panel test, cell count and lymphocytes subset, symptom severity score, posttreatment liver biopsy, and endoscopic retrograde cholangiopancreatography at 6 months and 2 years. All patients had a significant decrease in peripheral total lymphocyte (1,629 +/- 462 to 426 +/- 57; p < 0.01) and CD4 cell count (782 +/- 200 to 144 +/- 21; p < 0.05) with consequent decrease of CD4:CD8 ratio (3.82 +/- 1.96 to 1.84 +/- 0.69; p = 0.09). This was associated with a quantifiable decrease in the hepatic inflammatory infiltrate on liver biopsy. No significant changes were found in symptom scores, liver panel tests, or cholangiograms. The drug was well-tolerated and two of four patients reported remission of their inflammatory bowel disease symptoms. Cladribine decreases the hepatic lymphocytic inflammatory infiltrate in early-stage PSC, which did not translate into any short-term symptomatic, biochemical, or radiologic improvements. Further studies with long-term follow-up are needed to assess if this anti-inflammatory effect can modify the progression of disease.
authors: Division of Gastroenterology and Hepatology, Scripps Clinic, La Jolla, California 92037, USA.
authors: A
authors: A
authors: Duchini
authors: Z M
authors: ZM
authors: Younossi
authors: A
authors: A
authors: Saven
authors: G M
authors: GM
authors: Bordin
authors: H J
authors: HJ
authors: Knowles
authors: P J
authors: PJ
authors: Pockros
mesh_terms: D000328:Adult; D015209:Cholangitis, Sclerosing / Q000188:drug therapy*; D017338:Cladribine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
chemical_list: D007166:Immunosuppressive Agents; D017338:Cladribine