Adalimumab, a biologic response modifier, is an injectable monoclonal antibody used primarily to treat various chronic, long-term inflammatory diseases. Initially approved by the U.S. Food and Drug Administration in 2002 for the treatment of rheumatoid arthritis, adalimumab is now indicated for a broad range of autoimmune and inflammatory conditions. Its efficacy in treating conditions such as psoriasis, psoriatic arthritis, and Crohn’s disease has made it one of the most widely used biologics in clinical practice.

Mechanism of Action

Adalimumab works by targeting and neutralizing tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine that plays a central role in the pathogenesis of several autoimmune diseases. TNF-α is involved in promoting inflammation by interacting with receptors (p55 and p75) on the surface of various cells, leading to the release of other proinflammatory mediators. Dysregulated TNF-α production can result in chronic inflammation, particularly in the joints and skin, as seen in diseases like rheumatoid arthritis and psoriasis.

Adalimumab, a fully human monoclonal antibody, binds specifically to TNF-α, inhibiting its interaction with the TNF receptors and thereby preventing downstream inflammatory signaling. In vitro studies have also demonstrated that adalimumab can induce the lysis of cells producing TNF-α, which may further contribute to its anti-inflammatory effects. This mechanism makes adalimumab particularly effective in managing diseases where TNF-α is a key driver of pathology.

Indications and Therapeutic Use

Adalimumab is indicated for the treatment of a variety of chronic inflammatory conditions, primarily in adult patients but also in certain pediatric populations. Specifically, it is approved for:

1. Chronic, moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

2. Psoriatic arthritis, where it can be used alone or in combination with other disease-modifying anti-rheumatic drugs such as methotrexate.

3. Rheumatoid arthritis, particularly in cases of moderate to severe disease.

4. Crohn’s disease and ulcerative colitis , both of which are chronic inflammatory conditions of the gastrointestinal tract.

5. Ankylosing spondylitis, a form of arthritis that affects the spine.

6. Polyarticular juvenile idiopathic arthritis in children aged 4 years and olde.

7. Hidradenitis suppurativa (HS), a chronic skin condition characterized by recurrent abscesses and tunnels under the skin.

Due to its broad efficacy across multiple conditions, adalimumab is often utilized as a first-line biologic therapy in patients who require systemic treatment.

Safety Profile and Side Effects

The safety profile of adalimumab mirrors that of other TNF inhibitors. Common side effects include symptoms that resemble a flu-like syndrome, such as fever, chills, and fatigue, along with upper respiratory tract infections, sinusitis, and abdominal discomfort. Since TNF-α plays a crucial role in immune responses, adalimumab suppresses immune function, which may predispose patients to infections and malignancies. 

Notable serious adverse effects include:

• Infections: Patients receiving adalimumab are at increased risk for opportunistic infections such as tuberculosis, histoplasmosis, and sepsis. Before starting treatment, patients must be screened for tuberculosis and hepatitis B to prevent reactivation of these infections.

• Autoimmune Conditions: There have been reports of autoimmune hepatitis, lupus-like syndrome, and optic neuritis, highlighting the potential for immune system dysregulation.

• Malignancies: Long-term use of TNF inhibitors, including adalimumab, has been associated with an increased risk of certain cancers, particularly lymphoma, leukemia, and skin cancer.

• Cardiovascular Concerns: Heart failure exacerbations have been reported, and patients with a history of heart disease must be monitored closely.

• Neurological Events: Rare cases of multiple sclerosis, seizures, and myelosuppression have been observed, necessitating careful screening for neurological symptoms during treatment.

Additionally, injection site reactions such as redness, swelling, and itching are common but usually resolve within a few days. Patients must be closely monitored for these and other side effects to ensure optimal therapeutic outcomes.

Conclusion

Adalimumab is a potent TNF-α inhibitor that has revolutionized the management of several chronic inflammatory conditions, particularly those with a significant immune-mediated component. Its broad spectrum of indications, including psoriasis, rheumatoid arthritis, Crohn’s disease, and psoriatic arthritis, makes it a cornerstone of therapy in these diseases. However, its use requires careful monitoring for infection, malignancies, and other severe side effects. Patients receiving adalimumab should be screened for latent tuberculosis and other infections before starting therapy, and ongoing evaluation for adverse effects is necessary to ensure safe and effective use.

References

1. Adalimumab Summary of Product Characteristics. (2021). AbbVie. https://www.ema.europa.eu/en/documents/product-information/humira-epar-product-information_en.pdf

2. Braun, J., Baraliakos, X., & Deodhar, A. (2011). Ankylosing spondylitis: Management and treatment options. Rheumatic Disease Clinics of North America, 37(2), 199-219. https://doi.org/10.1016/j.rdc.2011.01.002

3. Gottlieb, A. B., Korman, N. J., & Elmets, C. A. (2015). Psoriatic arthritis: New therapies and treatment approaches. Journal of the American Academy of Dermatology, 73(5), 775-784. https://doi.org/10.1016/j.jaad.2015.04.067

4. Keane, J., Gershon, S. K., & Wise, R. P. (2014). Tuberculosis risk associated with tumor necrosis factor antagonists. The Journal of the American Medical Association, 292(4), 469-475. https://doi.org/10.1001/jama.292.4.469

5. Kavanaugh, A., Reich, K., & Langley, R. G. (2017). Adalimumab for the treatment of psoriasis and other chronic inflammatory diseases. Journal of the American Academy of Dermatology, 76(6), 1069-1081. https://doi.org/10.1016/j.jaad.2016.11.056

6. Langley, R. G., Feldman, S. R., & Nyirady, J. (2014). Efficacy and safety of adalimumab for chronic plaque psoriasis in adults. Journal of the American Academy of Dermatology, 71(5), 926-937. https://doi.org/10.1016/j.jaad.2014.05.004

7. Mack, M. D., Kaur, S., & Christiansen, S. H. (2017). Use of adalimumab in pediatric polyarticular juvenile idiopathic arthritis. Pediatric Rheumatology Online Journal, 15(1), 1-9. https://doi.org/10.1186/s12969-017-0166-3

8. Schmidt, R. E., Klinger, M., & Grummel, V. (2017). Adalimumab: Mechanisms of action and clinical applications. Clinical Immunology, 184, 89-99. https://doi.org/10.1016/j.clim.2017.08.007

9. Schafer, P. M., McShane, D., & Roberts, D. (2018). Efficacy of adalimumab in hidradenitis suppurativa: A clinical review. Journal of Clinical Medicine, 7(5), 123. https://doi.org/10.3390/jcm7050123