Humira (adalimumab) and Xeljanz (tofacitinib) are drugs used in the treatment of rheumatoid arthritis. Rheumatoid arthritis is a chronic disease caused by the body’s immune system attacking healthy tissue. This immune response causes pain, stiffness, and swelling in the joints. Humira is used to reduce signs and symptoms of rheumatoid arthritis in adult patients with moderate to severe rheumatoid arthritis. Humira is also indicated for Juvenile Idiopathic Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Crohn’s Disease, Ulcerative Colitis, and Plaque Psoriasis. Xeljanz is indicated for the treatment of adult patients with moderate to severe rheumatoid arthritis who have not responded to methotrexate or cannot tolerate it.

How do Humira and Xeljanz work

Xeljanz is a Janus kinase (JAK) inhibitor. JAKs are chemicals that trigger inflammation. Inflammation is swelling, redness, and pain that occur when the body is trying to repair an injury. Rheumatoid arthritis is due to inflammation from an immune response. Xeljanz acts to decrease this immune response.

Humira also works on the immune system but it works on Tumor Necrosis Factor (TNF). TNF is a naturally occurring chemical that is involved in the inflammatory and immune response. It is found in the joints of patients with rheumatoid arthritis. Humira blocks the action of TNF.

Both medications can be used in combination with methotrexate and non-biologic disease modifying antirheumatic drugs (DMARDs).

Efficacy of Humira versus Xeljanz

In a 12-month study, 717 patients who were on stable doses of methotrexate were randomly assigned to receive additional therapy with 5 mg of Xeljanz twice daily, 10 mg of Xeljanz twice daily, 40 mg of Humira once every 2 weeks, or a placebo. A placebo is a pill or treatment that does not have any active ingredients. It is used as a control to prevent bias which might occur when a patient believes they feel better just because they have received a treatment. The results were determined by whether the treatment resulted in a 20% improvement in the American College of Rheumatology scale. This scale is used to find out how severe a patient’s Rheumatoid Arthritis is.

After 6 months, 20% improvement in the American College of Rheumatology scale response rates were higher among patients receiving 5 mg or 10 mg of Xeljanz (51.5% and 52.6%, respectively) and among those receiving Humira (47.2%) than among those receiving placebo (28.3%). This study concluded that in patients with rheumatoid arthritis receiving methotrexate, Xeljanz was significantly superior to placebo and similar to Humira in efficacy.

In another study, 384 patients received placebo, Xeljanz at 1, 3, 5, 10, or 15 mg given by mouth twice a day, Humira at 40 mg injected under the skin every 2 weeks (total of 6 injections) followed by Xeljanz at 5 mg twice a day for 12 weeks.

A 20% improvement in the American College of Rheumatology scale response rates was achieved in 39.2% (3 mg), 59.2% (5 mg), 70.5% (10 mg), and 71.9% (15 mg) of patients in the Xeljanz group and 35.9% of patients in the Humira group, compared with 22.0% of patients receiving placebo.

Neither of these studies tested if Xeljanz worked better than Humira, but it was seen that Xeljanz was just as effective as Humira in rheumatoid arthritis patients already on methotrexate.

How are Humira and Xeljanz administered for Rheumatoid Arthritis

Xeljanz is administered as a 5 mg tablet by mouth twice daily.

Humira is administered as a 40 mg injection under the skin every other week.

Side effects of Humira and Xeljanz

The most common side effects of Humira are infections, injection site reactions, headache and rash. More serious side effects include, congestive heart failure, erythema multiforme, Stevens-Johnson syndrome, agranulocytosis, aplastic anemia, erythrocytosis, leukopenia, pancytopenia, thrombocytopenia, hepatic failure, anaphylaxis, cancer, immune hypersensitivity reaction, T-cell lymphoma, hepatosplenic, demyelinating disease of central nervous system, legionella pneumonia, Tuberculosis, listeriosis.

Conclusion

It appears that Xeljanz is as effective as Humira. Studies were not designed to test if Xeljanz worked better than Humira. A drawback of Xeljanz is twice daily dosing, which might be difficult to remember. However, if a patient has a phobia of needles, he or she might prefer an oral drug. Overall, it is easier to receive just 1 injection every 2 weeks if it is tolerable. Xeljanz is new to the market so its long term side effects may not be discovered yet. Humira has more studies backing its effectiveness. Also, Humira has more than one indication which is important for formulary considerations.

References:

Humira Prescribing Information

Xeljanz Prescribing Information

Van Vollenhoven RF, Fleischmann R, Cohen S, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012;367(6):508-19.

Fleischmann R, Cutolo M, Genovese MC, et al. Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. Arthritis Rheum. 2012;64(3):617-29.

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