Adalimumab (Humira) is a disease-modifying antirheumatic drug (DMARD) labeled for the adult treatment of moderately to severely active rheumatoid arthritis. It is a recombinant human immunoglobulin G1 monoclonal antibody that specifically binds and inhibits the inflammatory cytokine tumor necrosis factor (TNF)α.¹

SAFETY

There have been rare instances of serious infections, malignancies, and neurologic reactions with TNF antagonists, including adalimumab.^1–4 Serious infections can be fatal and include sepsis, opportunistic infections, invasive fungal infections (e.g., histoplasmosis, coccidioidomycosis, blastomycosis, aspergillosis, candidiasis), and tuberculosis. Although rare, increased rates of lymphomas and malignancies (including, but not limited to, nonmelanoma skin, lung, or breast cancers) have been observed with the use of TNF antagonists.^1,2 Adalimumab may rarely cause new-onset or exacerbations of neurologic disorders (e.g., paresthesia, tremor) or central nervous system-demyelinating diseases (e.g., optic neuritis, multiple sclerosis); caution should be exercised in patients with preexisting disease.¹ The TNF antagonists, including adalimumab, have also been found to increase the risk of hepatitis B virus reactivation in chronic carriers.¹ Cases of worsening heart failure have been reported with adalimumab.¹ There is insufficient evidence to suggest differences among TNF antagonists with regard to incidence of serious adverse events.⁵ Adalimumab is U.S. Food and Drug Administration pregnancy category B.¹

TOLERABILITY

Adalimumab is well tolerated and the discontinuation rate because of adverse effects is similar to placebo (7 and 4 percent, respectively).¹ Mild injection site reactions consisting of erythema and/or pain, itching, or swelling will occur in one in five patients and rarely necessitates drug discontinuation.¹ Nonserious infection, including upper respiratory infection, bronchitis, and urinary tract infection, at a rate of one per patient-year will likely occur.¹ However, most patients can continue therapy after infection resolution.¹ Other adverse effects are rash and headache, which occur in less than 5 percent of patients.¹

EFFECTIVENESS

Adalimumab has been studied in adult patients with moderate to severe rheumatoid arthritis as an early single-agent intervention, as a substitute for traditional DMARDs in patients not receiving benefit, and in combination with traditional DMARDs.

In patients with early aggressive rheumatoid arthritis, adalimumab produces similar results as methotrexate after one year of therapy.⁶ When used alone in early aggressive rheumatoid arthritis, adalimumab therapy can be expected to result in 23 percent of patients achieving remission and 41 percent of patients exhibiting clinical response after one year.⁶ However, when combined with methotrexate, the remission rates nearly double (43 percent) and response rates increase significantly (62 percent).⁶ After two years of combined therapy, benefit should still be evident, with close to one half of patients achieving remission, whereas only one fourth of patients on single-agent therapy will achieve remission.⁶

Adalimumab has also demonstrated benefit when substituted for or added to traditional DMARDs (e.g., methotrexate, leflunomide [Arava], sulfasalazine [Azulfidine], hydroxychloroquine [Plaquenil]) in patients who do not receive full benefit from their existing therapy. Over the short term (three months), 32 percent of patients who do not receive benefit with traditional DMARDs will experience a major clinical response when adalimumab is substituted.⁷ Clinical response is significantly better (41 to 43 percent response rate) if adalimumab is added to the existing therapy. This benefit appears to be most significant if the existing regimen contains methotrexate.⁷

There have been no direct comparisons between adalimumab and traditional DMARDs other than methotrexate. Likewise, TNF-alpha antagonists have not been compared directly, but adjusted indirect comparisons indicate similar response rates.⁸

PRICE

Adalimumab costs approximately $1,662 per month, which is the same cost of the TNF-alpha inhibitor etanercept (Enbrel). The cost of methotrexate is approximately $13 to $85 per month.

SIMPLICITY

Adalimumab can be used as monotherapy or in combination with methotrexate or other traditional DMARDs. It should not be used in combination with anakinra (Kineret), and its use with other TNF antagonists is not recommended. The dose is 40 mg injected subcutaneously every other week. Adalimumab is dispensed in a prefilled, single-use pen or syringe for self-administration. It must be stored in the refrigerator. Adalimumab should not be initiated in patients with an active infection and should be discontinued if a serious infection occurs. Patients who experience weight loss, cough, fever, shortness of breath, or fatigue should discontinue the medication immediately and be evaluated for the presence of infection.⁴ Patients should be evaluated for latent tuberculosis infection before drug administration and monitored for signs and symptoms of active tuberculosis disease while on therapy. Those at risk of hepatitis B virus infection should be evaluated for carrier status before adalimumab initiation. Live vaccines should not be administered concurrently in patients receiving adalimumab.¹

Bottom line

Adalimumab used alone offers little benefit over the traditional first-line agent, methotrexate. However, it increases remission rates when combined with methotrexate in early aggressive rheumatoid arthritis and when combined with traditional DMARDs in those who have not derived benefit from existing regimens. Most patients experience few side effects; however, rare, serious adverse events can occur.