Study in RA Shows No Rise in Lymphoma Risk with Tofacitinib

Oct 10, 2017

A recent study found that treatment with the JAK inhibitor, tofacitinib (Xeljanz) among patients with rheumatoid arthritis (RA) has not led to an increase in the incidence of lymphoma above what is expected for patients with this disease receiving other biologic therapies. 

JAK inhibitors are a promising new family of medications for the treatment of alopecia areata. Like most biologic therapies used for skin disease, they downregulate the body’s immune surveillance, placing patients who take them at increased risk for certain infections and malignancies. A recent study by Dr. Mariette and colleagues from University of Paris-Sud examined the rates of lymphomas associated with use of the JAK inhibitor, tofacitinib (Xeljanz) in 6,194 patients with rheumatoid arthritis (RA). The study concluded that treatment with tofacitinib was not associated with an increased incidence of lymphoma above what is expected for patients with RA receiving other biologic therapies. The results showed that incidence rate of lymphoma in these patients on tofacitinib was 0.10 (95% CI 0.06-0.15) per 100 patient-years, and standardized incidence ratio (SIR) was 2.62 (95% CI 1.58-4.09). In this analysis, almost 80% of the patients were women, and the median age was 60. The majority of patients received 10 mg twice daily dose.

The thought of trying to treat one disease and then increasing the risk for another is very grim. That is the scary reality when we use many medications for autoimmune diseases, including systemic prednisone, methotrexate or biologics. However, it is very reassuring that the tofacitinib SIR value is actually lower than those seen for other widely used biologic therapies, including adalimumab (Humira, SIR 2.74), etanercept (Enbrel, 3.45), infliximab (Remicade, 6.40), and golimumab (Simponi, 4.97).

How do we interpret all of this data? And, what does this mean for alopecia areata patients? Chronic inflammation in several autoimmune diseases has been associated with the development of malignancies. In particular, patients with RA, regardless of treatment regimens, have malignancies such as lymphomas, myelomas and lung cancer more frequently than the general population. Therefore, the relationship between lymphomas and RA is complex, as RA patients have elevated risk for lymphoma, particularly those with high levels of inflammation and severe disease. The good news is that unlike patient with RA, high incidences in lymphoma have never been described in patients with alopecia areata population. Nevertheless, Tofacitinib’s action on the immune system warrants close monitoring of adverse events, including lymphomas. With the increasing number of patients with AA treated with JAK inhibitors, careful collection and analysis such as performed in this study should be conducted.

For more information please refer to the following article:
Mariette X, Chen C, Biswas P, et al. Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program. Arthritis Care Res (Hoboken). 2017 Sep 21. doi: 10.1002/acr.23421. [Epub ahead of print]

Author: Dr. Natasha Atanaskova Mesinkovska, Chief Scientific Officer

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