An Open-label Pilot Trial of Cladibrine (2-Chlorodeoxyadenosine) in Patients with Primary Sclerosing Cholangitis

• Published in: Journal of clinical gastroenterology Vol. 31; no. 4; pp. 292 - 296
• Main Authors: Duchini, A, Younossi, Z M, Saven, A, Bordin, G M, Knowles, H J, Pockros, P J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01-12-2000; Lippincott Williams & Wilkins
• Subjects: Adult; Biological and medical sciences; Cholangitis, Sclerosing - drug therapy; Cladribine - therapeutic use; Digestive system; Female; Humans; Immunosuppressive Agents - therapeutic use; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Pilot Projects; Human; Chemotherapy; Treatment; Analog; Primary; Digestive diseases; Clinical trial; Nucleoside; Biliary tract disease; Sclerosing cholangitis; Mechanism of action
• ISSN: 0192-0790; 1539-2031
• DOI: 10.1097/00004836-200012000-00005

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 (1629 ± 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.