Adalimumab is a biologic medication prescribed to manage various autoimmune conditions, including rheumatoid arthritis, Crohn’s disease, and psoriasis. These conditions involve the immune system mistakenly attacking its own tissues, leading to inflammation and damage. Because adalimumab influences the immune system, understanding its potential interactions is important for patient safety and treatment outcomes.
How Adalimumab Works and Why Interactions Occur
Adalimumab functions as a tumor necrosis factor-alpha (TNF-alpha) inhibitor. TNF-alpha is a protein produced by the immune system that, when overactive, causes significant inflammation in autoimmune diseases. Adalimumab works by binding directly to both soluble and membrane-bound forms of TNF-alpha, neutralizing its inflammatory effects.
This binding prevents TNF-alpha from attaching to its specific receptors, TNFR1 and TNFR2, on immune cells. By blocking these interactions, adalimumab interrupts inflammatory signaling pathways, such as NF-κB and MAPK, which produce pro-inflammatory cytokines like interleukin-1, interleukin-6, and interleukin-8. This disruption reduces overall inflammation and diminishes the recruitment and activation of inflammatory cells at disease sites. However, by suppressing this immune response, adalimumab also lessens the body’s ability to fight infections, which forms the basis for many of its interactions and associated risks.
Interactions with Other Medications
Combining adalimumab with other medications requires careful consideration due to its impact on the immune system. Other biologic medications or strong immunosuppressants can significantly increase the risk of serious infections. For instance, co-administering adalimumab with other TNF blockers like etanercept, or with drugs such as anakinra, abatacept, rituximab, and Janus kinase (JAK) inhibitors (e.g., upadacitinib, tofacitinib), is generally not recommended. Using these powerful immune-suppressing agents together further weakens the body’s defenses against pathogens.
Methotrexate, an anti-inflammatory medication, is frequently prescribed alongside adalimumab for conditions like rheumatoid arthritis. This combination is often beneficial because methotrexate can slow down the removal of adalimumab from the body, potentially increasing its effectiveness. However, the combination still necessitates close monitoring for an increased risk of infection. Corticosteroids, which also suppress the immune system, can heighten the risk of infection when taken with adalimumab.
Adalimumab can also influence the metabolism of certain medications, such as warfarin, a blood thinner. The suppression of cytokine activity by adalimumab may affect cytochrome P450 enzymes in the liver, which are involved in drug metabolism, potentially decreasing warfarin’s blood levels and effects. Therefore, patients taking warfarin with adalimumab need closer monitoring of their INR (International Normalized Ratio) levels to ensure proper blood clotting.
Regarding herbal supplements, there is limited information on their safety when taken with adalimumab, as they are not tested like prescription medications for potential interactions. Caution is advised with supplements that might affect the immune system, such as Echinacea or astragalus. It is important to disclose all herbal and dietary supplement use to a healthcare provider. Most common over-the-counter pain relievers like ibuprofen or acetaminophen are generally considered safe to use with adalimumab, with no known direct interactions. Still, consulting a doctor about all medications, including OTC drugs, is a prudent step.
Vaccine Considerations
Vaccination protocols change for individuals receiving adalimumab. Live vaccines, which contain a weakened form of the virus, are generally not recommended for patients on adalimumab due to the risk of developing an actual infection from the vaccine itself.
Examples of live vaccines to avoid include:
- Measles, mumps, and rubella (MMR) vaccine
- Chickenpox (varicella) vaccine
- Nasal spray flu vaccine
- BCG (tuberculosis)
- Rotavirus
- Oral typhoid
- Yellow fever
- Shingles vaccine (Zostavax, not Shingrix)
If a live vaccine is necessary, it may be advised to stop adalimumab treatment for at least 12 months before vaccination, and then wait approximately 4 weeks after vaccination before restarting the medication.
Inactivated vaccines, which contain killed viruses or bacteria, are generally considered safe and are often recommended for individuals on adalimumab. These include:
- Standard injectable flu shot
- Tetanus shots
- COVID-19 vaccines
- Pneumococcal vaccines
- Human papillomavirus (HPV) vaccine
- Diphtheria, pertussis, hepatitis A and B, and polio vaccines
While these vaccines are safe, the immune response in patients taking adalimumab might be reduced compared to individuals with a fully functioning immune system. Whenever possible, it is advisable for patients to receive all necessary vaccinations before initiating adalimumab therapy.
Interactions with Pre-existing Health Conditions
Adalimumab’s immune-modulating effects mean that pre-existing health conditions must be thoroughly evaluated before and during treatment. Active infections pose a significant concern, as adalimumab should not be started if a patient has an ongoing infection, and it can worsen existing ones. The medication increases susceptibility to various serious infections, including bacterial, viral, fungal, and opportunistic pathogens.
Tuberculosis (TB) screening is a standard requirement before initiating adalimumab, and ongoing monitoring for TB is also advised during therapy. This includes testing for latent TB infection, which, if positive, should be treated before adalimumab administration to prevent reactivation of the disease. Reactivation of latent TB or new onset active TB can occur, sometimes presenting as disseminated or extrapulmonary disease.
Adalimumab, along with other TNF blockers, has been associated with new onset or worsening of congestive heart failure (CHF), particularly in individuals with moderate to severe forms of the condition. Patients with heart failure need careful monitoring for signs such as shortness of breath, sudden weight gain, or swelling in the ankles or feet. Caution is advised for those with existing heart conditions.
There is also a recognized risk of new onset or exacerbation of demyelinating diseases affecting the central nervous system (CNS) or peripheral nervous system (PNS). These conditions include multiple sclerosis (MS), optic neuritis, and Guillain-Barré syndrome. Neurological symptoms can emerge anywhere from several months to over two years after starting adalimumab. Therefore, healthcare providers exercise caution when considering adalimumab for patients with a history of these disorders or a family history of demyelinating conditions.
Suppressing the immune system with adalimumab could potentially affect the body’s natural ability to fight cancer cells. There is an increased chance of certain cancers, including lymphoma, and specifically a rare and often fatal type called hepatosplenic T-cell lymphoma, especially in young males with inflammatory bowel disease receiving combination therapy. An increased risk of specific skin cancers, such as basal cell and squamous cell carcinoma, has also been observed. While overall malignancy rates in adalimumab clinical trials are generally consistent with those expected in the general population, the incidence of lymphoma in rheumatoid arthritis patients may be elevated due to the underlying disease itself. Some studies suggest an increased risk of lymphoma and leukemia with long-term TNF inhibitor use over two years.