{"id":1152,"date":"2012-11-01T00:00:41","date_gmt":"2012-11-01T07:00:41","guid":{"rendered":"http:\/\/rhochistj.org\/RhoChiPost\/?p=1152"},"modified":"2014-02-19T12:11:06","modified_gmt":"2014-02-19T19:11:06","slug":"new-drug-review-tofacitinib-xeljanz","status":"publish","type":"post","link":"https:\/\/rhochistj.org\/RhoChiPost\/new-drug-review-tofacitinib-xeljanz\/","title":{"rendered":"New Drug Review: Tofacitinib (Xeljanz\u00ae)"},"content":{"rendered":"

By: Jessica Lee, PharmD Candidate c\/o 2013<\/span><\/p>\n

–<\/p>\n

Rheumatoid arthritis (RA) is an autoimmune disease in which the immune system attacks healthy tissue, causing inflammation of the joints and potential harm to other organs.1<\/sup>\u00a0 It affects 0.5-1% of the adult population and is more prevalent in the seventh decade of life.1<\/sup>\u00a0 These patients tend to experience joint pain and stiffness; over time, the joints can become deformed and lose their range of motion.1<\/sup>\u00a0 Current treatment options for RA consist of nonpharmacological therapy, including physical and occupational therapies, and pharmacological therapy, namely the disease-modifying antirheumatic drugs (DMARDs).1<\/sup>\u00a0 DMARDs include nonbiologic agents (e.g. <\/i>methotrexate) and biologic agents (e.g. <\/i>adalimumab [Humira\u00ae]).1<\/sup><\/p>\n

The biologic agents target the proinflammatory cytokines, such as tumor necrosis factor (TNF) and interleukins (IL), which have roles in lymphocyte activation, proliferation, and function.1<\/sup>\u00a0 These cytokines can cause inflammation and damage to the joints and surrounding tissue.1<\/sup>\u00a0 The current treatment guidelines from the American College of Rheumatology includes eight biologic agents, which are further categorized into anti-TNF agents [etanercept (Enbrel\u00ae), infliximab (Remicade\u00ae), adalimumab (Humira\u00ae), certolizumab (Cimzia\u00ae), golimumab (Simponi\u00ae)] and non-TNF biologic agents [abatacept (Orencia\u00ae), rituximab (Rituxan\u00ae), and tocilizumab (Actemra\u00ae)].2<\/sup><\/p>\n

On November 6, 2012, the FDA approved Pfizer\u2019s new agent, tofacitinib (Xeljanz\u00ae), for the treatment of moderately to severely active RA in patients who have failed methotrexate.3<\/sup> \u00a0It is approved to be used as monotherapy or in combination with methotrexate or other nonbiologic DMARDs.4<\/sup> \u00a0It is the first, new oral DMARD to be approved in more than 10 years, which can be advantageous to patients who lack the dexterity to perform self-injections.5<\/sup> \u00a0Unlike the previous biologic agents that act on extracellular targets, tofacitinib takes on a new approach by targeting the intracellular pathways of the inflammatory cytokines.6<\/sup>\u00a0 Tofacitinib is a Janus kinase (JAK) inhibitor (specifically at JAK1 and JAK3), which modulates the immune response by interrupting signal-transduction activity for multiple cytokines, including interleukins 2, 4, 6, 7, 9, 15 and 21.6<\/sup>\u00a0 The FDA approved tofacitinib to be given twice daily as a 5 milligram dose; the safety of a 10 milligram twice daily dose is still under investigation.3<\/sup>\u00a0 Several clinical trials have shown reduction in symptoms and improved physical functioning in patients receiving tofacitinib.7<\/sup> \u00a0One study found tofacitinib monotherapy to be significantly superior to methotrexate in reducing signs \/ symptoms and inhibiting structural damage.5<\/sup><\/p>\n

The most common side effects are upper respiratory infections, headache, diarrhea, and nasopharyngitis.4<\/sup>\u00a0 Adverse effects of tofacitinib include serious infections (e.g. <\/i>tuberculosis and herpes zoster), malignancies (e.g.<\/i> lymphomas), gastric perforations, decreased neutrophil and lymphocyte counts, and elevated lipid levels.4<\/sup>\u00a0 This side effect profile is similar to other anti-TNF agents.4\u00a0 <\/sup>Post-marketing surveillance will be conducted in order to study the long term effects of tofacitinib in heart disease, cancer, and serious infections.3<\/sup><\/p>\n

Overall, as a JAK inhibitor, tofacitinib has the potential to be helpful in treating other autoimmune diseases.8<\/sup>\u00a0 Clinical trials have been set up to assess its function in psoriasis, ulcerative colitis, and Crohn\u2019s disease.8<\/sup><\/p>\n

SOURCES:<\/span><\/b><\/p>\n

    \n
  1. Schuna AA.\u00a0 Chapter 100.\u00a0 Rheumatoid Arthritis.\u00a0 In: Talbert RL, DiPiro JT, Matzke GR, Posey LM, Wells BG, Yee GC, eds.\u00a0 Pharmacotherapy: A Pathophysiologic Approach<\/i>.\u00a0 Eighth ed.\u00a0 New York: McGraw-Hill; 2011.\u00a0 http:\/\/www.accesspharmacy.com\/content.aspx?aID=7997207.<\/a>\u00a0 Accessed November 8, 2012.<\/li>\n
  2. PL Detail-Document, DMARDs in the treatment of rheumatoid arthritis.\u00a0 Pharmacist\u2019s Letter\/Prescriber\u2019s Letter.\u00a0 July 2012.<\/li>\n
  3. U.S.\u00a0 Food and Drug Administration.\u00a0 FDA approves Xeljanz for rheumatoid arthritis.\u00a0 Published November 6, 2012.\u00a0 Accessed November 8, 2012.<\/li>\n
  4. Xeljanz [package insert].\u00a0 New York, NY: Pfizer, Inc.; 2012.<\/li>\n
  5. Pfizer announces data for investigational compound tofacitinib in rheumatoid arthritis to be presented at the AmericanCollege of Rheumatology 2012 Annual Meeting.\u00a0 Pfizer.\u00a0 Published September 17, 2012.\u00a0 Accessed November 8, 2012.<\/li>\n
  6. van Vollenhoven RF, Fleishmann R, Cohen S, et al.<\/i>\u00a0 Tofacitinib or adalimumab versus placebo in rheumatoid arthritis.\u00a0 N Engl J Med<\/i>.\u00a0 2012;367(6):508-19.<\/li>\n
  7. Feischmann R, Kremer J, Cush J, et al.<\/i>\u00a0 Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis.\u00a0 N Engl J Med<\/i>.\u00a0 2012;367(6):495-507.<\/li>\n
  8. Sandborn WJ, Ghosh S, Panes J, et al.<\/i>\u00a0 Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis.\u00a0 N Engl J Med<\/i>.\u00a0 2012;367(7):616-24.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    By: Jessica Lee, PharmD Candidate c\/o 2013 – Rheumatoid arthritis (RA) is an autoimmune disease in which the immune system attacks healthy tissue, causing inflammation of the joints and potential harm to other organs.1\u00a0 It affects 0.5-1% of the adult population and is more prevalent in the seventh decade of life.1\u00a0 These patients tend to…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[1523,1105,1825,343,193,40,716,1623,198,15,163,13,2229,2227,899,420,2232,35,314,1808,2251,39,139,1713,601,97,1120,101,363,1625,657,47,671,2140,1820,1736,220,99,187,21,2252,453,1161,333,2120,16,17,1061,2119,2030],"class_list":["post-1152","post","type-post","status-publish","format-standard","hentry","category-clinical","tag-abatacept","tag-adalimumab","tag-agents","tag-and","tag-annual","tag-cancer","tag-certolizumab","tag-combination","tag-daily","tag-disease","tag-dose","tag-drug","tag-drugs","tag-ebola-virus-disease","tag-etanercept","tag-factor","tag-fda","tag-food","tag-for","tag-golimumab","tag-guidelines","tag-heart","tag-inflammation","tag-infliximab","tag-inhibitor","tag-july","tag-lipid","tag-november","tag-of","tag-or","tag-oral","tag-pain","tag-r","tag-ra","tag-reduction","tag-respiratory","tag-review","tag-september","tag-side","tag-study","tag-symptoms","tag-system","tag-therapy","tag-tocilizumab","tag-tofacitinib","tag-treatment","tag-trial","tag-with","tag-xeljanz","tag-zoster"],"views":877,"_links":{"self":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/1152","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/comments?post=1152"}],"version-history":[{"count":0,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/1152\/revisions"}],"wp:attachment":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/media?parent=1152"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/categories?post=1152"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/tags?post=1152"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}