From the FDA Drug Label
The malignancies in HUMIRA-treated patients in the controlled and uncontrolled portions of the studies were similar in type and number to what would be expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race).1 In controlled trials of other TNF blockers in adult patients at higher risk for malignancies (i.e., patients with COPD with a significant smoking history and cyclophosphamide-treated patients with Wegener’s granulomatosis), a greater portion of malignancies occurred in the TNF blocker group compared to the control group In the controlled portions of clinical trials of all the TNF-blockers in adults, more cases of lymphoma have been observed among TNF-blocker-treated patients compared to control-treated patients In the controlled portions of 39 global HUMIRA clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, 2 lymphomas occurred among 7973 HUMIRA-treated patients versus 1 among 4848 control-treated patients. The observed rate of lymphomas was approximately 0.11 per 100 patient-years. This is approximately 3-fold higher than expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race). Post-marketing cases of acute and chronic leukemia have been reported in association with TNF-blocker use in RA and other indications. Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blockers (initiation of therapy ≤ 18 years of age), of which HUMIRA is a member. Approximately half the cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including HUMIRA.
Key Points:
- The rate of lymphomas in HUMIRA-treated patients is approximately 3-fold higher than expected in the general U.S. population.
- More cases of lymphoma have been observed among TNF-blocker-treated patients compared to control-treated patients.
- Post-marketing cases of acute and chronic leukemia have been reported in association with TNF-blocker use.
- Malignancies, including lymphomas, have been reported in children, adolescents, and young adults treated with TNF-blockers.
- HUMIRA may increase the risk of lymphoma, including non-Hodgkin's lymphoma (NHL) 1.
- Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers including HUMIRA 1.
The use of HUMIRA may be associated with an increased risk of lymphoma, including non-Hodgkin's lymphoma (NHL).
From the Research
Taking Humira (adalimumab) may be associated with a small increased risk of non-Hodgkin lymphoma (NHL), but the absolute risk remains low and the benefits of controlling severe autoimmune disease often outweigh the potential cancer risks. Humira is a TNF-alpha inhibitor used to treat various autoimmune conditions, and it carries a black box warning regarding malignancy risk, including lymphoma 2. The risk appears to be small but real, with studies suggesting that patients taking TNF inhibitors like Humira may have a slightly higher chance of developing NHL compared to the general population. However, it's essential to understand that the underlying inflammatory diseases themselves (like rheumatoid arthritis or Crohn's disease) are independently associated with an increased lymphoma risk, making it difficult to determine how much additional risk is specifically from the medication 3.
Some key points to consider:
- A study published in 2018 found that the observed lymphoma rate in patients taking adalimumab was lower than the estimated background rate, and the upper bound of the one-sided 95% CI of the observed rate was lower than double the estimated rate 3.
- Another study published in 2022 found that diabetes mellitus was associated with poor survival outcomes in patients with B-cell NHL, but concurrent metformin use in DM patients with NHL may be associated with improved survival outcomes 4.
- The benefits of controlling severe autoimmune disease with Humira often outweigh the potential cancer risks, and patients taking Humira should be monitored regularly and report any concerning symptoms like persistent fever, night sweats, weight loss, or enlarged lymph nodes to their healthcare provider promptly.
In terms of the most recent and highest quality study, the 2018 study by 3 provides the most relevant evidence for the association between Humira and NHL risk. Based on this study, the risk of NHL associated with Humira appears to be low, and the benefits of treatment often outweigh the risks. Patients taking Humira should be aware of the potential risks and benefits and discuss any concerns with their healthcare provider.