New Drug Review: Tofacitinib (Xeljanz®)

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  It affects 0.5-1% of the adult population and is more prevalent in the seventh decade of life.1  These patients tend to experience joint pain and stiffness; over time, the joints can become deformed and lose their range of motion.1  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  DMARDs include nonbiologic agents (e.g. methotrexate) and biologic agents (e.g. adalimumab [Humira®]).1

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  These cytokines can cause inflammation and damage to the joints and surrounding tissue.1  The current treatment guidelines from the American College of Rheumatology includes eight biologic agents, which are further categorized into anti-TNF agents [etanercept (Enbrel®), infliximab (Remicade®), adalimumab (Humira®), certolizumab (Cimzia®), golimumab (Simponi®)] and non-TNF biologic agents [abatacept (Orencia®), rituximab (Rituxan®), and tocilizumab (Actemra®)].2

On November 6, 2012, the FDA approved Pfizer’s new agent, tofacitinib (Xeljanz®), for the treatment of moderately to severely active RA in patients who have failed methotrexate.3  It is approved to be used as monotherapy or in combination with methotrexate or other nonbiologic DMARDs.4  It 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  Unlike 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  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  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  Several clinical trials have shown reduction in symptoms and improved physical functioning in patients receiving tofacitinib.7  One study found tofacitinib monotherapy to be significantly superior to methotrexate in reducing signs / symptoms and inhibiting structural damage.5

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

Overall, as a JAK inhibitor, tofacitinib has the potential to be helpful in treating other autoimmune diseases.8  Clinical trials have been set up to assess its function in psoriasis, ulcerative colitis, and Crohn’s disease.8


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