{"id":1554,"date":"2011-04-28T23:05:23","date_gmt":"2011-04-29T03:05:23","guid":{"rendered":"http:\/\/blogs.nejm.org\/?p=1554"},"modified":"2015-06-04T15:23:43","modified_gmt":"2015-06-04T19:23:43","slug":"hepatitis-c-week-is-upon-us","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/hepatitis-c-week-is-upon-us\/2011\/04\/28\/","title":{"rendered":"Hepatitis C Week is Upon Us"},"content":{"rendered":"<p><a href=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2011\/04\/rumsfeld1.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignright size-full wp-image-1559\" title=\"rumsfeld\" src=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2011\/04\/rumsfeld1.jpg\" alt=\"\" width=\"198\" height=\"255\" \/><\/a>After many &#8212; and I mean <em>many<\/em> &#8212; years of telling patients that new hepatitis C drugs were &#8220;coming soon,&#8221; that time has finally come.<\/p>\n<p>An FDA Advisory Panel yesterday favorably reviewed the <a href=\"http:\/\/health.usnews.com\/health-news\/family-health\/digestive-disorders\/articles\/2011\/04\/28\/new-hepatitis-c-drug-close-to-gaining-fda-approval\" target=\"_blank\">HCV protease inhibitor boceprevir<\/a>; today telaprevir <a href=\"http:\/\/online.wsj.com\/article\/BT-CO-20110428-725590.html\">got the same unanimous report<\/a>. The FDA will\u00a0 certainly follow with approval for both drugs, and hence they will be available for actual use soon.<\/p>\n<p>While these are undoubtedly huge advances for patients with HCV genotype 1 &#8212; who faced a 30-40% chance of cure with IF\/ribavirin now, compared with up to 80% by adding one of the new drugs &#8212; many questions remain about how they will be used, and in whom.<\/p>\n<p>In no particular order, and without even trying to be comprehensive, here are some of the &#8220;<a href=\"http:\/\/www.amiclarke.com\/uu.htm\" target=\"_blank\">known unknowns<\/a>&#8220;:<\/p>\n<ul>\n<li>How will clinicians choose between them?<\/li>\n<li>Is a 4-week lead in with IF\/RBV (as was done with the boceprevir studies) necessary?\u00a0 Additionally, is it <em>useful<\/em>, by identifying &#8220;null&#8221; responders who will have a higher rate of developing treatment failure and PI resistance?\u00a0 Could starting all three drugs simultaneously improve outcome?<\/li>\n<li>How long should treatment be?\u00a0 Will this vary depending on HCV RNA kinetics from person-to-person?\u00a0 Seems like this is a situation ripe for sophisticated modeling, and that \u00a0more frequent HCV RNA monitoring (especially early) will inform this decision.<\/li>\n<li>How will patients in the chaotic real world tolerate these drugs?\u00a0 Interferon\/ribavirin is already no picnic, and adding these additional meds will mean additional side effects.<\/li>\n<li>Related: \u00a0Besides the signature toxicities (telaprevir &#8212; rash and anemia, boceprevir &#8212; anemia and dysgeusia), what other side effects will appear with more widespread use?\u00a0 Note that it&#8217;s not a question of <em>if<\/em> these side effects will occur, it&#8217;s <em>when <\/em>will occur, and <em>what<\/em> they will be.<\/li>\n<li>How will resistance be assayed?\u00a0 Will genotype testing become commercially available?\u00a0 If so, what new combination of letters and numbers (i.e. mutations) will need to be memorized?<\/li>\n<li>How do these advances influence treatment decisions about the patients who don&#8217;t have HCV genotype 1, especially those with genotype 4? \u00a0I suspect not at all, at least for now.<\/li>\n<li>How will compliance be with these three-times a day regimens?\u00a0 Will it improve over the course of therapy, or will patients get &#8220;pill fatigue.&#8221;\u00a0 We know they will get <em>regular <\/em>fatigue &#8212; I have yet to see a patient receiving interferon who didn&#8217;t mention this as a side effect.<\/li>\n<li>View from 20,000 feet:\u00a0 If someone is currently very stable &#8212; with low risk of HCV disease progression &#8212; should they &#8220;act now&#8221; or wait for even better, less toxic options?\u00a0 Given the huge effort in HCV drug development, how long before we have treatments for HCV that are comparably simple to HIV therapy?\u00a0 Is a single-pill combination tablet too much to ask?\u00a0 Remember, for HIV, such a treatment would have been unimaginable in 1996; less than 10 years later it was the mostly widely-used HIV combination in the country, and remains so today.<\/li>\n<li>Who will be the HCV Providers?\u00a0 Will the legacy of gastroenterologists&#8217; leading the way in hepatitis therapy continue, or will this <em>Infectious Disease <\/em>finally be embraced by <em>Infectious Disease Doctors<\/em>?\u00a0 (Italics represent my view.)<\/li>\n<li>How much will the new drugs cost?\u00a0 Will they be covered for all patients?\u00a0 How about for those who have a favorable IL-28B genotype &#8212; and would be likely responders to IF\/RBV alone?<\/li>\n<li>How will our HIV co-infected patients respond?\u00a0 Data are extremely limited &#8212; and the drug-drug interactions promise to be unbelievably complex. \u00a0As of April 28 2011, we only have data on use of telaprevir with either EFV or ATV\/r.<\/li>\n<li>How do you design an HCV clinical trial once these drugs are approved?\u00a0 Will all &#8220;control&#8221; arms now need to be IF\/RBV + something-previr?<\/li>\n<\/ul>\n<p>Answers to some of these questions will come with formal FDA approval, which will necessarily include some &#8220;package insert&#8221; indications for therapy.<\/p>\n<p>But stay on your toes, because it seems highly likely that this is one therapeutic area in ID that truly lends itself to the cliche, &#8220;moving target.&#8221;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>After many &#8212; and I mean many &#8212; years of telling patients that new hepatitis C drugs were &#8220;coming soon,&#8221; that time has finally come. An FDA Advisory Panel yesterday favorably reviewed the HCV protease inhibitor boceprevir; today telaprevir got the same unanimous report. The FDA will\u00a0 certainly follow with approval for both drugs, and [&hellip;]<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,5,8,10],"tags":[119,348,408,513,810,905],"class_list":["post-1554","post","type-post","status-publish","format-standard","hentry","category-health-care","category-infectious-diseases","category-patient-care","category-research","tag-boceprevir","tag-fda","tag-hcv","tag-interferon","tag-ribavirin","tag-telaprevir"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/1554","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/comments?post=1554"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/1554\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=1554"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=1554"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=1554"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}