[메디칼업저버 양영구 기자] There is no evidence that Januskinase (JAK) inhibitors increase the risk of cancer compared to tumor necrosis factor (TNF) inhibitors and biologic antirheumatic drugs (bDMARDs), a study has found.
Recently, a research team led by Dr. Viking Huss from the Karolinska Research Center in Sweden published the results of a study evaluating the cancer risk of JAK inhibitors, TNF-α inhibitors, and bDMARDs in rheumatoid and psoriatic arthritis patients.
In conclusion, there is no evidence that JAK inhibitors increase the risk of cancer other than non-melanoma skin cancer (NMSC) in patients with rheumatoid arthritis and psoriatic arthritis compared with other treatments.
JAK Inhibitors Concern Increased Risk of Cancer ↑
Previously, concerns were raised that JAK inhibitors could increase the patient’s cancer risk through pharmacological mechanisms.
In fact, in 2021, the US Food and Drug Administration (FDA) reviewed a large randomized safety study of Pfizer’s JAK inhibitor Xeljanz (ingredient name tofacitinib) and found that it increased the risk of serious events associated with the heart, including heart attack, stroke, cancer, blood clots and death
The basis is the ORAL Surveillance study, a post-marketing safety investigation. This study included patients with rheumatoid arthritis who had at least one risk factor for cardiovascular disease and were over 50 years of age.
The entire patient group was randomly assigned to either the Xeljanz 5 mg twice daily dose group or 10 mg twice daily group and the TNF inhibitor treatment group.
As a final result of the evaluation of the two doses of Xeljanz, the malignant tumor incidence rate per 100 person-years was 1.13 in the Xeljanz group and 0.77 in the TNF blocker group, indicating that the risk of malignancy was significant. higher in the Xeljanz group by 48% (HR 1.48; 95% CI 1.04 to 2.09).
Additionally, the Xeljanz group had higher rates of major cardiovascular events, thrombosis, and death, as well as higher rates of lung cancer and lymphoma, compared to the TNF inhibitor group.
This also led to the publication of a warning by the European Medicines Agency (EMA).
When I actually analyzed it… there was no ‘difference’
To evaluate whether JAK inhibitors actually increase the risk of cancer compared to TNF inhibitors, the research team estimated the incidence ratio and overall risk of cancer by dividing patients with rheumatoid arthritis and psoriatic arthritis with patients who treated with JAK inhibitors and TNF inhibitors.
From January 2016 to December 2020, the Swedish Rheumatology Register, the National Patient Register, the Longitudinal Database for Insurance and Labor Market Research, the Prescription Drug Register, the Population and Causes of Death Register, the National Cancer, etc. perform
The research team classified the data into a TNF inhibitor group, a non-TNF bDMARD inhibitor group, and a JAK inhibitor group.
TNF inhibitors included Humira (adalimumab), Cimzia (sertorizumab), Enbrel (etanercept), Symphony (golimumab), and Remicade (infliximab).
Non-TNF inhibitor bDMARDs included Rituxan (Rituximab), Orencia (Abatacept), Actemra (Tocilizumab), and Kevzara (Sarirumab), while JAK inhibitors included Olumient (Baricitinib) and Xeljanz, Rinvoq (upadacitinib), and others .
Among patients with rheumatoid arthritis, there were 1967 patients in the JAK inhibitor group, 3520 patients in the non-TNF bDMARD inhibitor group, and 7343 patients in the TNF group. Their average follow-up period was 1.95, 2.83, and 2.49 years, respectively.
Among patients with psoriatic arthritis, there were 379 patients in the JAK inhibitor group, 185 patients in the non-TNF bDMARD inhibitor group, and 4185 patients in the TNF inhibitor group. Their follow-up period was 1.52 years, 2.25 years, and 2.44 years, respectively.
The research team set the primary target point as the incidence rate of cancers other than non-melanoma skin cancer (NMSC). Types of cancer included prostate cancer, testicular cancer, and breast cancer.
As a result of the analysis, among rheumatoid arthritis patients, there were 38 cases of cancer other than NMSC in patients treated with JAK inhibitors, and 213 cases in the TNF inhibitor group (HR 0.94; 95% CI 0.65 to 1.38) . There were 141 cases in the non-TNF bDMARD inhibitor group.
Incident NMSC was found in 59 cases in the JAK inhibitor group and 189 cases in the TNF inhibitor group (HR 1.39; 95% CI 1.01 to 1.91). There were 126 cases in the non-TNF bDMARD inhibitor group.
In all three groups, the incidence of NMSC was higher than the general population. In particular, JAK inhibitors had a higher risk of NMSC than TNF inhibitors.
In fact, the NMSC hazard ratio (HR) of Xeljanz versus TNF inhibitors was 1.56 (95% CI 0.83 to 2.92) and Olumiant was 1.37 (95% CI 0.97 to 1.92).
In patients with psoriatic arthritis, the incidence of non-NMSC cancers in the TNF inhibitor group reached 73, but only 5 in the JAK inhibitor group (HR 1.88; 95% CI 0.68 to 5.16). For NMSC, there were 8 cases in the JAK inhibitor group and 73 cases in the TNF inhibitor group, with a hazard ratio of 2.05 (95% CI 0.79 to 5.31).
“There is no evidence that JAK inhibitor treatment increases the risk of cancer in the short term compared to TNF inhibitor treatment in patients with rheumatoid arthritis or psoriatic arthritis,” said the research team. “The risk of NMSC may be increased in patients with rheumatoid arthritis.”
