title: Peginterferon Lambda-1a Is Associated with a Low Incidence of Autoimmune Thyroid Disease in Chronic Hepatitis C.
abstract: Peginterferon alfa (alfa) increases the risk of autoimmune disease. Peginterferon lambda-1a (Lambda) acts through a receptor with a more liver-specific distribution compared to the alfa receptor. In a phase-2b study, 525 treatment-naive patients with chronic hepatitis C virus (HCV) infection received ribavirin and Lambda interferon (120, 180, or 240 μg) or alfa interferon (180 μg) for 24 (genotypes 2 and 3) or 48 (genotypes 1 and 4) weeks. Retrospective analysis found that adverse events of MedDRA-coded thyroid dysfunction and abnormal levels of thyroid-stimulating hormone (TSH) were significantly more frequent with alfa versus Lambda (12% versus 2.6% and 15.2% versus 3.4%, respectively, both P<0.0001). Most Lambda recipients with abnormal TSH had levels below the lower limit of normal; the frequency of low and high TSH was similar in alfa recipients with abnormal TSH. Blinded review by an endocrinologist found that new-onset primary hypothyroidism or painless thyroiditis was less frequent with Lambda versus alfa (0.5% and 1.8% versus 5.3% and 7.5%, respectively, P<0.0001). Most TSH elevations reflected new-onset hypothyroidism requiring treatment, while most markedly suppressed TSH values reflected probable painless thyroiditis and resolved without sequelae. In conclusion, HCV-infected patients treated with Lambda/ribavirin experienced fewer adverse events of thyroid dysfunction compared with patients treated with alfa/ribavirin.
authors.affiliation: 1 Zymogenetics, Bristol-Myers Squibb , Seattle, Washington.
authors.forename: Paul
authors.initials: P
authors.lastname: Fredlund
authors.affiliation: 1 Zymogenetics, Bristol-Myers Squibb , Seattle, Washington.
authors.forename: Jan
authors.initials: J
authors.lastname: Hillson
authors.affiliation: 1 Zymogenetics, Bristol-Myers Squibb , Seattle, Washington.
authors.forename: Todd
authors.initials: T
authors.lastname: Gray
authors.affiliation: 1 Zymogenetics, Bristol-Myers Squibb , Seattle, Washington.
authors.forename: Lynn
authors.initials: L
authors.lastname: Shemanski
authors.affiliation: 2 Global Pharmacovigilance and Epidemiology, Bristol-Myers Squibb , Hopewell, New Jersey.
authors.forename: Dessislava
authors.initials: D
authors.lastname: Dimitrova
authors.affiliation: 3 Research and Development, Bristol-Myers Squibb , Wallingford, Connecticut.
authors.forename: Subasree
authors.initials: S
authors.lastname: Srinivasan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D007378:Interleukins / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced*; D013972:Thyrotropin / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000410:Alanine Transaminase; D000998:Antiviral Agents; D001219:Aspartate Aminotransferases; D016898:Interferon-alpha; D007378:Interleukins; D011092:Polyethylene Glycols; D012254:Ribavirin; D013972:Thyrotropin; C000600496:peginterferon lambda-1a; D000095022:Interferon Lambda