Humira (Adalimumab) is classified as a TNF-blocker (tumor necrosis factor) blocker.
TNF-blockers are used for a variety of inflammatory conditions, including dermatologic, arthritic and gastrointestinal diseases.
Humira is most commonly used in adults with rheumatoid arthritis (RA) or psoriatic arthritis (PsA). It can improve not only the symptoms of these diseases, but can inhibit their progression and improve physical function.
TNF-blockers aren't without their share are side effects unfortunately and Humira is no exception.
The risk of cancer and related malignancies (e.g. lymphoma) has been reported with TNF-blockers like Humira, but data is mixed, especially when it comes to risks in adults.
For children however, the risks are clearer, necessitating a 'black box warning' requirement by the FDA in the prescribing information for the drug.
Below we discuss these risks and more.
Cancer Risk In Children
Malignancies, including Hodgkin's and non-Hodgkin's lymphoma, have been reported among children and young adults (18 years old or younger) who received a TNF-blocker (such as Humira).
The prescribing information for Humira has a black box warning regarding malignancies in children and adolescents:
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers including HUMIRA.
Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have occurred in adolescent and young adults with inflammatory bowel disease treated with TNF blockers including HUMIRA
Although TNF-blockers are associated with cancer in children, there is a lot we still don't know as the majority of children examined in studies that were affected had concomitant disease states (e.g. Crohn's disease or ulcerative colitis), which are already risk factors for cancer.
The true incidence of cancer and related malignancies is uncertain with the use of a TNF-blocker alone.
Nevertheless, due to the risks in children (perhaps due to Humira decreasing the ability of the immune system to fight infection), it is recommended that prior to treatment initiation, children who will receive Humira should be brought up to date with all immunizations.
Humira is associated with an increased risk of certain cancers in children and young adults 18 years old and younger, although there could be confounding factors.
Cancer Risk In Adults
When it comes to risks for adults, there is even more ambiguity on just how much, if at all, Humira raises the risk of certain types of cancer.
However, the prescribing information makes a pretty clear statement regarding lymphoma risk:
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.
It goes on to say:
This [incidence of lymphoma] is approximately 3-fold higher than expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race).
Although the prescribing information states an increased rate of lymphoma, things get a little murkier when examining the studies referenced.
In the study the quote above is from, it is true that the observed rate of lymphomas was increased in patients taking Humira.
There were approximately 0.11 cases per 100 patient-years after Humira administration, which is about approximately 3-fold higher than expected in the general population.
It is important to note that study (and others) discuss a number of caveats that need to be taken into consideration with the results. These include:
- Individuals with rheumatoid arthritis, especially those with highly active disease, are already at a higher risk for the development of lymphoma, regardless of whether or not they are taking a TNF-blocker.
- Most individuals in the clinical trials have had chronic exposure to immunosuppressant therapies, which is a risk factor for the development of certain malignancies.
Numerous large studies, after adjusting for certain factors such as age, gender, rheumatoid arthritis duration and concomitant medication, found that the risk of lymphoma development in patients after exposure to TNF-blockers (such as Humira) is no higher than the risk in patients with the disease who did not receive treatment with them.
One of the largest studies reviewing the safety of Humira reported the following:
Overall malignancy rates for adalimumab-treated patients [Humira treated patients] were as expected for the general population; the incidence of lymphoma was increased in patients with RA, but within the range expected in RA without anti-TNF therapy; non-melanoma skin cancer incidence was raised in RA, Ps and CD. In all indications, death rates were lower than, or equivalent to, those expected in the general population.
As we can see from all the above information, Humira, and all TNF-blockers are associated with an increased rate of lymphoma, but there are confounding factors.
Nevertheless, if there truly is an increased risk of lymphoma with Humira alone, it is rare.
Humira is associated with a small increased risk of lymphoma, however, it isn't known whether or not this is due to the drug alone or other factors (e.g. disease progression, concomitant medications).
Non-Melanoma Skin Cancer
In addition to lymphomas, Humira is associated with non-melanoma skin cancer. There is ambiguity with this as well.
The prescribing information for Humira cites a study where the rate of adult patients with non-melanoma skin cancer was 0.8 per 100 patient-years with Humira treated patients versus 0.2 per 100 patient-years among control-treated patients.
Like lymphoma, there are questions regarding the true risk. One large study reported the following:
Other studies acknowledge an increased risk of nonmelanoma skin cancer in patients with psoriasis treated with adalimumab [Humira]. However, nonmelanoma skin cancer tends to appear very early after the introduction of adalimumab, and is only rarely found in patients receiving adalimumab for the treatment of rheumatoid arthritis. Therefore it may be concluded that nonmelanoma skin cancer is not necessarily caused by adalimumab therapy, but by previous psoriasis therapies, most likely by phototherapy using UV light.
As there may be an increased risk of non-melanoma skin cancer, it is recommended for health care providers to thoroughly examine all patients prior to initiating Humira.
In particular, individuals with a medical history of prior immunosuppressant therapy or psoriasis patients with a history of photochemotherapy treatment need to be extensively evaluated prior to and during treatment with Humira.
Humira is associated with a small increased risk of non-melanoma skin cancer, which can occur early after treatment initiation. It is not known whether this is due to Humira itself, or progression/prior treatment of disease.
The risks for cancer and related malignancies with Humira is low, and not completely understood. There are more likely than not additional factors at play, including the fact that the diseases Humira is indicated to treat already puts individuals at an increased risk.
It is nonetheless important to be educated about certain signs and symptoms. These symptoms include:
- Abdominal pain
- Persistent fever
- Night sweats
- Weight loss
If any of the above occur, it is important to discuss them with your doctor.
- Humira Prescribing Information. RxAbbie
- A Guide To Drug Safety. FDA
- Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists. PubMed
- Cancer prevalence estimates based on tumour registry data in the Surveillance, Epidemiology, and End Results (SEER) Program. PubMed
- Rheumatoid Arthritis and Risk of Malignant Lymphoma: Is the Risk Still Increased? PubMed
- Rheumatoid arthritis and lymphoma: Incidence, pathogenesis, biology, and outcome. PubMed
- Safety and tolerability of adalimumab for the treatment of psoriasis: a review summarizing 15 years of real-life experience. PubMed
- Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn's disease. PubMed
- Biologic Safety in Psoriasis. PubMed