Pharmaceutical-Approval Update

19 Jun

Adalimumab (Humira™)

Manufacturer: Abbott Laboratories, North Chicago, IL Indication: Treatment of rheumatoid arthritis (RA) Drug Class: Adalimumab is a recombinant human immunoglobulin G (IgG1) monoclonal antibody that is specific for human tumor necrosis factor (TNF). It was created using phage-display technology, resulting in an antibody with human-derived heavy chain and light chain variable regions and human IgG1:K constant regions. Adalimumab is produced by recombinant DNA technology in a mammalian cell expression system and is purified by a process that includes specific steps of viral inactivation and removal. Consisting of 1,330 amino acids, it has a molecular weight of approximately 148 kd.

Uniqueness of Drug: Adalimumab is the first human monoclonal antibody approved for reducing the signs and symptoms of RA, and for inhibiting the progression of structural damage, in adults with moderately to severely active RA who have not responded adequately to one or more traditional disease-modifying antirheumatic drugs (DMARDs). Boxed Warning—Risk of Infections: Cases of tuberculosis (frequently disseminated or extrapulmonary at clinical presentation) have been observed in patients receiving adali-mumab. A tuberculin skin test should be used to evaluate patients for latent tuberculosis infection, which, if present, should be treated before adalimumab therapy is initiated.
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Warnings Infections

Serious infections and sepsis, sometimes resulting in fatalities, have been reported with the use of TNF-blocking agents, including adalimumab. Many of these infections have occurred in patients receiving concomitant immunosuppressive therapies that can predispose them to tuberculosis in addition to their existing RA. Invasive opportunistic fungal infections have been also observed in patients receiving TNF-blocking agents, including adalimumab.

Adalimumab therapy should not be initiated in patients with any active chronic or localized infections. If new infections develop during therapy, close monitoring is essential. If serious infections develop, adalimumab administration should be discontinued. Physicians should exercise caution when considering the use of adalimumab in patients with a history of recurrent infections or underlying conditions, which may predispose them to infections, or in patients who have resided in regions where tuberculosis and histoplasmosis are endemic. Physicians should carefully consider the benefits and risks of adalimumab treatment before initiating therapy. Demyelinating Disease

The use of TNF-blocking agents, including adalimumab, has been associated with rare cases of exacerbation of clinical symptoms and with radiographic evidence of demyelinating disease. Prescribers should use caution in considering adalimumab for patients with pre-existing or recent-onset central nervous system demyelinating disorders. Malignancy Lymphomas have been observed in patients taking TNF-blocking agents, including adalimumab. In clinical trials, the incidence of lymphoma was higher than the expected rate in patients who had taken adalimumab than in the general population. Patients with RA, particularly those with highly active disease, may be at a higher risk (up to several-fold) for lymphoma, although the role of TNF blockers in the development of malignancy is not known. canadian antibiotics

Precautions: Allergic reactions have been observed in approximately 1% of patients receiving adalimumab. If an ana-phylactic reaction or other serious allergic reactions occur, administration of adalimumab should be discontinued immediately and appropriate therapy should be initiated.

The first injection should be performed under the supervision of a qualified health care professional. If patients or caregivers plan to administer adalimumab, they should be instructed in injection techniques; their ability to inject the drug as a subcutaneous (SQ) dose should also be assessed to ensure proper administration technique.

It is possible that TNF-blocking agents, including adali-mumab, might affect host defenses against infections and malignancies because TNF mediates inflammation and modulates cellular immune responses.

As observed with TNF-blocking agents, adalimumab has been associated with tuberculosis in clinical trials. Tuberculosis was observed with all dosages, but the incidence of tuberculosis reactivations was especially greater when the adalimumab doses were higher than the recommended dose. All patients recovered from tuberculosis after standard antimicrobial therapy. No deaths were attributable to tuberculosis during the clinical trials.

Dosage: The recommended dose of adalimumab for adult patients with RA is 40 mg, administered every other week as an SQ injection. Methotrexate, glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, or other DMARDs may be continued during treatment with adalimumab. Some patients who are not taking concomitant methotrexate may derive additional benefit from increasing the dosing frequency of adalimumab to 40 mg every week.
Adalimumab is intended for use under the guidance and supervision of a physician. Patients may self-inject adalimumab if their physician determines that it is appropriate and with medical follow-up, as necessary, after proper training in injection technique.

The adalimumab solution in the syringe and in the vial should be carefully inspected visually for particulate matter and discoloration before SQ administration. If particulates and discolorations are noted, the product should not be used. P&T Committee Considerations: Adalimumab has been approved to reduce the signs and symptoms of RA, and to inhibit the process of structural damage, in adult patients with moderately to severely active RA who have not benefited sufficiently after treatment with one or more DMARDS. Adali-mumab offers convenience as an every-other-week SQ injetion. A specially designed prefilled syringe will be available, making the self-injection process easier for patients whose hands have been damaged or deformed by the disease.

Adalimumab can be used alone or in combination with methotrexate. The efficacy of adalimumb was assessed by evaluating improvement in RA signs and symptoms response scores and in inhibition of the progression of structural damage, as measured by bone changes in x-ray films. Twenty-two percent (14 of 63 patients) experienced improvement in signs and symptoms of RA as early as one week after the beginning of treatment.

Adalimumab must be used with caution. The most serious adverse drug events associated with it are infections, neurological effects, and certain malignancies of the lymphoid system. Compared with the general population, patients with RA, particularly those with active disease, appear to be at greater risk for the development of lymphomas. Patients with RA should discuss therapy options with their health care providers.

Adalimumab is appropriate for inclusion on the formulary, but prescribers should first gain a thorough awareness of the patient’s general health before initiating therapy.
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The manufacturer’s wholesale price of adalimumab is $13,500 for a year’s treatment, about the same as for etanercept (Enbrel®, Immunex, Wyeth-Ayerst) and infliximab (Remi-cade®, Centocor); both cost upwards of $13,940 a year to administer. The list price from the manufacturer or the wholesale acquisition cost (WAC) for 2- to 40-mg prefilled syringes of adalimumab plus two alcohol preparations is $1,045.28.