{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T02:48:32Z","timestamp":1782874112980,"version":"3.54.5"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1126,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>In comparison with peginterferon\/ribavirin alone, boceprevir with peginterferon\/ribavirin significantly improves sustained virological response (SVR) rates in patients with chronic hepatitis C virus (HCV) genotype 1 infections, but treatment failure remains a significant problem. Using phase 3 trial databases, we sought to develop stopping rules for patients destined to fail boceprevir-based combination therapy in order to minimize drug toxicity, resistance, and costs in the face of ultimate futility. Exploratory post hoc analyses using data from the Serine Protease Inhibitor Therapy 2 (SPRINT-2) study (treatment-naive patients) and the Retreatment With HCV Serine Protease Inhibitor Boceprevir and Pegintron\/Rebetol 2 (RESPOND-2) study (treatment-experienced patients) were undertaken to determine whether protocol-specified stopping rules (detectable HCV RNA at week 24 for SPRINT-2 and at week 12 for RESPOND-2) could be refined and harmonized. In SPRINT-2, a week 12 rule with an HCV RNA cutoff of \u2265100 IU\/mL would have discontinued therapy in 65 of 195 failures (sensitivity = 33%) without sacrificing a single SVR among 475 successes (specificity = 100%). Viral variants emerged after week 12 in 36 of the 49 evaluable patients (73%) who would have discontinued at week 12 using a \u2265100 IU\/mL stopping rule. In RESPOND-2, five of six patients with week 12 HCV RNA levels between the lower limit of detection (9.3 IU\/mL) and the lower limit of quantification (25 IU\/mL) who continued therapy despite the protocol-stipulated futility rule achieved SVR; one additional patient with a week 12 HCV RNA level of 148 IU\/mL also continued therapy, had undetectable HCV RNA at week 16, and attained SVR.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>Although a stopping rule of detectable HCV RNA at week 12 would have forfeited some SVR cases, week 12 HCV RNA levels \u2265100 IU\/mL almost universally predicted a failure to achieve SVR in both treatment-naive and treatment-experienced patients. In boceprevir recipients, the combination of 2 stopping rules\u2014an HCV RNA level \u2265100 IU\/mL at week 12 and detectable HCV RNA at week 24\u2014maximized the early discontinuation of futile therapy and minimized premature treatment discontinuation. (HEPATOLOGY 2012)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.25865","type":"journal-article","created":{"date-parts":[[2012,5,22]],"date-time":"2012-05-22T19:42:03Z","timestamp":1337715723000},"page":"567-575","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":49,"title":["Refinement of stopping rules during treatment of hepatitis C genotype 1 infection with boceprevir and peginterferon\/ribavirin"],"prefix":"10.1097","volume":"56","author":[{"given":"Ira M.","family":"Jacobson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Marcellin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Zeuzem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark 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