Adalimumab

Adalimumab is a recombinant fully human monoclonal antibody belonging to the tumor necrosis factor, or TNF, blocker class of biologic medicines. It binds specifically to tumor necrosis factor-alpha, a signaling protein involved in inflammation, and prevents TNF from interacting with its receptors. By reducing excessive TNF activity, adalimumab can decrease inflammation and related tissue damage in several immune-mediated diseases. It is administered by subcutaneous injection and can be self-injected by appropriately trained patients or caregivers. Depending on the indication, treatment may be given every other week or at other approved intervals, with some conditions requiring an initial loading regimen. Adalimumab is used across rheumatologic, dermatologic, gastrointestinal and ophthalmic conditions, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or axial spondyloarthritis, Crohn’s disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, juvenile idiopathic arthritis and non-infectious uveitis. Its clinical importance comes from its ability to selectively inhibit a major inflammatory pathway and provide sustained disease control in patients with moderate to severe inflammatory disorders. Because TNF inhibition can reduce normal immune defenses, appropriate screening, vaccination review and monitoring for infections and other adverse effects are important during treatment.

Adalimumab was developed as a fully human monoclonal antibody directed against TNF-alpha using recombinant DNA and phage-display technology. The original U.S. biologics license application was submitted for rheumatoid arthritis, and the U.S. Food and Drug Administration granted initial approval on 31 December 2002 for the treatment of rheumatoid arthritis. Subsequent FDA approvals expanded its use to additional inflammatory and immune-mediated conditions, including juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa and non-infectious uveitis. In the European Union, Humira containing adalimumab received marketing authorisation on 8 September 2003, followed by numerous post-authorisation expansions and updates. Current European information includes rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, psoriasis, Crohn’s disease, ulcerative colitis, juvenile idiopathic arthritis, enthesitis-related arthritis, hidradenitis suppurativa and non-infectious uveitis. Indian regulatory records also document adalimumab products and additional indications, including rheumatoid arthritis, psoriatic arthritis, hidradenitis suppurativa, Crohn’s disease, ulcerative colitis, psoriasis and juvenile idiopathic arthritis. Major clinical development programmes included randomized studies across rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, psoriasis and other TNF-mediated inflammatory conditions.

Adalimumab is used for several moderate to severe inflammatory and immune-mediated disorders, with the exact approved indications and age requirements depending on the regulatory jurisdiction and product. In adults, established uses include moderately to severely active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis or other approved forms of axial spondyloarthritis, moderate to severe plaque psoriasis, Crohn’s disease, ulcerative colitis, hidradenitis suppurativa and non-infectious intermediate, posterior and panuveitis. Pediatric indications include polyarticular juvenile idiopathic arthritis, Crohn’s disease, ulcerative colitis, hidradenitis suppurativa and pediatric uveitis in specified age and weight groups. Adalimumab may be used as monotherapy or together with other treatments depending on the disease. In rheumatoid arthritis, it may be administered alone or with methotrexate or another appropriate disease-modifying antirheumatic medicine. Treatment selection should consider disease severity, previous therapies, contraindications, infection risk and the approved indication for the specific product.

Adalimumab is administered by subcutaneous injection, usually into the thigh or abdomen, and patients or caregivers may administer it after appropriate training. For adult rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, the usual dose is 40 mg every other week, although selected rheumatoid arthritis patients not receiving methotrexate may require a more frequent approved regimen. Crohn’s disease and ulcerative colitis generally require an initial loading regimen followed by maintenance dosing, while plaque psoriasis and adult uveitis generally use an initial 80 mg dose followed by 40 mg every other week. Hidradenitis suppurativa uses a higher induction regimen followed by weekly or every-other-week maintenance dosing depending on the approved regimen. Pediatric dosing is based primarily on age, body weight and indication. Treatment is generally continued while clinical benefit is maintained and adverse effects remain acceptable. The injection site should be rotated, and the medicine should be stored and handled according to the applicable product instructions.

Common side effects of adalimumab include injection-site reactions, upper respiratory infections, sinusitis, headache and rash. Patients may also experience nausea, abdominal discomfort, musculoskeletal symptoms, urinary infections or other mild infections depending on the treatment population. Injection-site reactions may include redness, swelling, itching or discomfort and are often temporary. Because adalimumab suppresses TNF-mediated immune activity, infections may occur more frequently or become more clinically significant in some patients. The frequency and severity of adverse effects can vary according to the underlying disease, age, concomitant medicines and individual risk factors. Most common reactions can be managed with appropriate clinical monitoring, supportive care or adjustment of treatment when necessary.

The most important serious risks associated with adalimumab are serious infections and malignancies. TNF blockade can increase the risk of tuberculosis, bacterial sepsis, invasive fungal infections and other opportunistic infections, and patients should be evaluated for latent tuberculosis before treatment and monitored for active tuberculosis during therapy. Hepatitis B virus reactivation can occur in susceptible patients and requires appropriate screening and monitoring. Serious hypersensitivity reactions, demyelinating disorders, cytopenias and pancytopenia, worsening or new-onset heart failure, lupus-like syndromes and autoimmune hepatitis have also been reported. Malignancies including lymphoma and other cancers have been reported, with particular concern regarding rare hepatosplenic T-cell lymphoma in certain young patients with inflammatory bowel disease receiving TNF blockers. Adalimumab should generally be discontinued or withheld when clinically significant serious infection or other serious toxicity develops, according to the nature and severity of the event.

Before initiating adalimumab, healthcare professionals should assess for active or latent tuberculosis, previous serious infections, hepatitis B infection, vaccination status and relevant neurological, cardiac or hematological conditions. Patients with active serious infections should not generally begin treatment until the infection has been appropriately addressed. Live vaccines should generally be avoided during treatment, while vaccination status should be reviewed before therapy when possible. Adalimumab should not generally be combined with other biologic medicines that produce overlapping immunosuppression, such as abatacept or anakinra, because of increased infection risk. Patients with heart failure, demyelinating disease or recurrent infections require particular clinical consideration. Drug interactions are generally related more to additive immunosuppression and changes in inflammatory activity than to conventional hepatic enzyme inhibition. Pregnancy, breastfeeding and the timing of vaccination should be discussed with the treating healthcare professional. Patients should also inform their healthcare team about all prescription medicines, over-the-counter medicines and biologic therapies being used.

Prescribers should confirm the exact indication, age and weight requirements, previous therapies and applicable dosing regimen before initiating adalimumab. Baseline evaluation should include infection history, tuberculosis assessment, hepatitis B status and vaccination review, with additional investigations guided by the patient's clinical condition. During therapy, patients should be monitored for fever, persistent cough, unexplained weight loss, recurrent infections, neurological symptoms, new cardiac symptoms, abnormal blood counts and other signs of serious adverse reactions. Patients should be counselled on correct subcutaneous injection technique, rotation of injection sites, appropriate storage and recognition of infection-related symptoms. Pharmacists should verify the product strength, formulation, dosing interval and storage requirements and should check for concurrent biologic immunosuppressants that may increase infection risk. When adalimumab is used for chronic inflammatory disease, treatment response should be assessed regularly and continued only when the expected clinical benefit remains appropriate. Biosimilar substitution and product interchange should follow applicable regulatory requirements and local prescribing and dispensing policies.