Xeljanz/Xeljanz XR (Tofacitinib/Tofacitinib XR), an Oral JAK Inhibitor, Now Approved for Adults with Active Psoriatic Arthritis

Xeljanz/Xeljanz XR (Tofacitinib/Tofacitinib XR), an Oral JAK Inhibitor, Now Approved for Adults with Active Psoriatic Arthritis

Psoriatic arthritis, a chronic inflammatory disease that affects the immune system, is characterized by swelling, stiffness, and joint or tendon pain that is often accompanied by skin and nail psoriasis.1,2 Although psoriatic arthritis most often affects the distal joints in the fingers and toes, the disease can also affect the lower back, wrists, knees, and ankles.3

Approximately 2.4 million people in the United States have psoriatic arthritis.1 More than 30% of patients with psoriasis have psoriatic arthritis, and more than 15% of those with psoriasis may have undiagnosed psoriatic arthritis.1

Psoriatic arthritis is associated with pain, itching, fatigue, limitations in physical function, and work disability—factors that can have a substantial impact on the patient’s quality of life.4 The disease is also associated with emotional duress that stems from frustration, embarrassment, and self-consciousness.4

Therapies for psoriatic arthritis include nonsteroidal anti-inflammatory drugs; immunosuppressant drugs; traditional disease-modifying antirheumatic drugs (DMARDs); an oral phosphodiesterase-4 inhibitor; and biologic drugs, including a T-cell inhibitor, tumor necrosis factor-alpha inhibitors, interleukin (IL)-17 antagonists, and an IL-12/23 antagonist.2,5 Recently, the first oral Janus kinase (JAK) inhibitor was added to the treatment options for patients with psoriatic arthritis.

Xeljanz/Xeljanz XR a New Oral Option for Active Psoriatic Arthritis

On December 14, 2017, the US Food and Drug Administration (FDA) approved a new indication for tofa­citinib/tofacitinib extended release (XR; Xeljanz/Xeljanz XR; Pfizer) for the treatment of adults with active psoriatic arthritis who have an inadequate response to, or cannot tolerate, methotrexate or other DMARDs.6 Tofacitinib/tofacitinib XR, an oral JAK inhibitor, is the first oral JAK inhibitor to be approved by the FDA for the treatment of active psoriatic arthritis and for moderate-to-severe rheumatoid arthritis (RA).6

Tofacitinib (5 mg twice daily) was initially approved by the FDA in 2012 as monotherapy or in combination with methotrexate or with other nonbiologic DMARDs for the treatment of adults with moderately to severely active RA.7 Tofacitinib XR (11 mg once daily) was initially approved by the FDA in 2016 for the treatment of patients with moderately to severely active RA.8

Mechanism of Action

Tofacitinib/tofacitinib XR inhibits the action of JAKs, which are intracellular enzymes that transmit signals from multiple cytokines or growth factor receptor interactions involved in the pathogenesis of psoriatic arthritis.9,10 These signals are implicated in immune-cell function and hematopoiesis. JAKs activate and phosphorylate signal transducers and activators of transcription (STATs), a process that affects intracellular activity, including gene expression.9 Tofacitinib inhibits the JAK-signaling pathway, thereby preventing the activation and phosphorylation of STATs.9 In addition, tofacitinib may regulate multiple pathways associated with the stimulation and proliferation of inflammatory cells in psoriatic arthritis.10,11

Dosing and Administration

For patients with psoriatic arthritis, the recommended dose of tofacitinib is 5 mg twice daily, and the recommended dose of tofacitinib XR is 11 mg once daily, both used in combination with nonbiologic DMARDs.9

Tofacitinib is available as a 5-mg tablet, and tofacitinib XR is available as an 11-mg tablet.9

Pivotal Clinical Trials

The safety and efficacy of tofacitinib were evaluated in 2 randomized, double-blind, placebo-controlled trials—OPAL Broaden and OPAL Beyond—that included 816 adult patients.9,10,12 Eligible patients had active psoriatic arthritis for at least 6 months and had received a stable dose of a nonbiologic DMARD at baseline.9 The primary end points in both studies were the American College of Rheumatology (ACR)20 response rate (20% improvement from baseline across several specific measures) and the change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at month 3.9

At 3 months in the OPAL Broaden study, patients who received tofacitinib had significantly greater (P ≤.05) ACR20, ACR50, and ACR70 response rates compared with placebo (Table 1).9 In the OPAL Beyond study, the difference between tofacitinib and placebo was significant (P ≤.05) in ACR20 and ACR50 responses, but not significant (P >.5) in ACR70 responses (Table 2).9

Xeljanz/Xeljanz XR (Tofacitinib/Tofacitinib XR), an Oral JAK Inhibitor, Now Approved for Adults with Active Psoriatic Arthritis

Xeljanz/Xeljanz XR (Tofacitinib/Tofacitinib XR), an Oral JAK Inhibitor, Now Approved for Adults with Active Psoriatic Arthritis

In both studies, patients who received tofacitinib 5 mg or 10 mg twice daily achieved a significantly greater (P ≤.05) improvement in physical functioning (as measured by HAQ-DI score) versus placebo at 3 months.9

Adverse Reactions

The most common (≥2% of patients who received tofacitinib monotherapy or in combination with DMARDs) adverse reactions reported during the first 3 months of treatment with tofacitinib 5 mg twice daily or tofacitinib 10 mg twice daily were upper respiratory tract infections, headache, diarrhea, and nasopharyngitis.9 The most common serious adverse reactions reported with tofacitinib were infections. Overall, 4% of patients who received tofacitinib and 3% of patients who received placebo discontinued treatment because of adverse reactions in the double-blind, placebo-controlled clinical trials.9

Tofacitinib has no contraindications.9

Drug Interactions

Tofacitinib/tofacitinib XR is not recommended for use in combination with biologic DMARDs or with potent immunosuppressant drugs, such as azathioprine and cy­closporine.9

The co-administration of potent cytochrome (CY) P450 CYP3A4 inhibitors (eg, ketoconazole) with tofacitinib increases the exposure of tofacitinib. For patients who receive a potent CYP3A4 inhibitor, the recommended dose of tofacitinib is 5 mg once daily.9

For patients who receive ≥1 concomitant drugs that result in moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (eg, fluconazole), the recommended dose of tofacitinib is 5 mg once daily.9

The co-administration of potent inducers of CYP3A4 (eg, rifampin) with tofacitinib may result in a reduction or a loss of clinical response to tofacitinib. The co-­administration of CYP3A4 inducers with tofacitinib is not recommended.9

Use in Specific Populations

Women of reproductive potential should use contraception during tofacitinib therapy and for at least 4 weeks after the last dose.9

In tofacitinib clinical studies, patients aged ≥65 years had more serious infections than younger patients.9

No dose adjustment is required for patients with mild hepatic impairment. For patients with moderate hepatic impairment, the recommended dose of tofacitinib is 5 mg once daily. Tofacitinib is not recommended in patients with severe hepatic impairment.9

For patients with mild renal impairment, no dose adjustment is needed. The recommended dose of tofacitinib for patients with moderate or severe renal impairment is 5 mg once daily.9

Warnings and Precautions

Tofacitinib was approved with a boxed warning about the risk for serious infections and malignancies, including lymphoma. Serious infections, including tuberculosis and bacterial, invasive fungal, viral, and other opportunistic infections, have been reported with tofacitinib.9

Lymphoma and other malignancies have been reported with tofacitinib, as well as an increased Epstein-Barr virus–associated posttransplant lymphoproliferative disorder in patients who received tofacitinib plus immunosuppressive drugs.9

Tofacitinib should be used with caution in patients at risk for gastrointestinal perforations.9

Patients should be monitored for changes in lymphocytes, neutrophils, hemoglobin, liver enzymes, and lipid levels.9

Immunizations should be updated before starting treatment with tofa­citinib. Live vaccines should not be administered with tofacitinib.9


The FDA approval of a new indication for tofacitinib and tofacitinib XR marks the availability of a novel oral option for appropriate patients with active psoriatic arthritis. In 2 clinical trials, tofacitinib demonstrated greater response rates in ACR20, ACR50, and ACR70 and in physical functionality, based on HAQ-DI assessment, compared with placebo.


  1. National Psoriasis Foundation. What is psoriatic arthritis? June 2017. www.psoriasis.org/sites/default/files/psoriatic_arthritis_fact_sheet_1.pdf. Accessed January 23, 2018.
  2. Mayo Clinic. Psoriatic arthritis. www.mayoclinic.org/diseases-conditions/psoriatic-arthritis/symptoms-causes/syc-20354076. Accessed January 23, 2018.
  3. National Psoriasis Foundation. About psoriatic arthritis. www.psoriasis.org/about-psoriatic-arthritis. Accessed January 24, 2018.
  4. Armstrong AW, Schupp C, Wu J, Bebo B. Quality of life and work productivity impairment among psoriasis patients: findings from the National Psoriasis Foundation survey data 2003-2011. PLoS One. 2012;7:e52935.
  5. National Psoriasis Foundation. Moderate to severe psoriasis and psoriatic arthritis: biologic drugs. www.psoriasis.org/about-psoriasis/treatments/biologics. Accessed January 25, 2018.
  6. Pfizer. Pfizer announces FDA approval of Xeljanz (tofacitinib) and Xeljanz XR for the treatment of active psoriatic arthritis. December 14, 2017. http://press.pfizer.com/press-release/pfizer-announces-fda-approval-xeljanz-tofacitinib-and-xeljanz-xr-treatment-active-psor. Accessed January 22, 2018.
  7. Pfizer. Multimedia: U.S. Food and Drug Administration approves Pfizer’s Xeljanz (tofacitinib citrate) for adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate. Press release. November 7, 2012. https://www.pfizer.com/news/press-release/press-release-detail/u_s_food_and_drug_administration_approves_pfizer_s_xeljanz_tofacitinib_citrate_for_adults_with_moderately_to_severely_active_rheumatoid_arthritis_ra_who_have_had_an_inadequate_response_or_intolerance_to_methotrexate. Accessed January 24, 2018.
  8. Pfizer. Pfizer announces FDA approval of Xeljanz XR (tofacitinib citrate) extended-release tablets, the first and only once-daily oral JAK inhibitor treatment for rheumatoid arthritis. February 24, 2016. www.pfizer.com/news/press-release/press-release-detail/pfizer_announces_fda_approval_of_xeljanz_xr_tofacitinib_citrate_extended_release_tablets_the_first_
    . Accessed January 23, 2018.
  9. Xeljanz/Xeljanz XR (tofacitinib) tablets/extended release tablets [prescribing information]. New York, NY: Pfizer; December 2017.
  10. Mease P, Hall S, FitzGerald O, et al. Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N Engl J Med. 2017;377:1537-1550.
  11. Gao W, McGarry T, Orr C, et al. Tofacitinib regulates synovial inflammation in psoriatic arthritis, inhibiting STAT activation and induction of negative feedback inhibitors. Ann Rheum Dis. 2016;75:311-315.
  12. Gladman D, Rigby W, Azevedo VF, et al. Tofacitinib for psoriatic arthritis in patients with an inadequate response to TNF inhibitors. N Engl J Med. 2017;377:1525-1536.

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