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Recombinant drug offers new option for aching joints

Joint tenderness, swelling, stiffness, pain, restricted range of motion ... these and other debilitating symptoms are the norm rather than exception for more than two million Americans afflicted by rheumatoid arthritis (RA). The disease typically manifests by periods of exacerbations and remissions, which tend to progress to joint degeneration, deformity, and significant disability.

According to Michael Schiff, M.D., rheumatologist and director of clinical research at the Denver Arthritis Clinic, "As many as 80% of patients do not get adequate relief, experience lifelong exacerbations and worsening of disease, and are refractory to treatment."

Two major players seem to contribute to joint pain and destruction in RA: tumor necrosis factor (TNF) and interleukin-1 (IL-1). Together, these cytokines elicit inflammation as well as cartilage and bone destruction. As a result, current pharmacologic treatments for RA revolve not only around treating the pain and inflammation but also attempt to slow disease progression.

Consistent with these goals, Kineret (anakinra, Amgen) recently received Food & Drug Administration approval for reducing signs and symptoms of moderate to severe RA in adults who have failed to respond adequately to one or more disease-modifying antirheumatic drugs (DMARDs). Anakinra is a recombinant form of the endogenous protein IL-1 receptor antagonist (IL-1Ra).

To explain the therapeutic target of anakinra, Rebecca Hamm, spokeswoman for Amgen, said, "In a normal individual, there's a balance of IL-1 and IL-1Ra. In RA patients, IL-1 is overexpressed." In other words, there is an excess of IL-1 in RA patients and not enough IL-1Ra, the endogenous antagonist, to compensate.

Anakinra, or recombinant IL-1Ra, reduces pain and inflammation by binding to IL-1 receptors and competitively inhibits IL-1 binding. Symptomatic improvements may be seen within four weeks of initiating therapy. Clinical trial results indicate that after six months of therapy, 38% of patients taking anakinra experienced more than a 20% reduction in signs and symptoms, compared with only 22% of patients experiencing significant relief with methotrexate, another commonly prescribed DMARD.

Anakinra is administered once daily via subcutaneous injection into the stomach, arms, or thighs. Each dose comes in a single-use prefilled glass syringe. Since RA patients often have dexterity issues, the Simpleject autoinjector system has been made available to assist patients with anakinra injections. Said Hamm, "The autoinjector's handle has a large, soft rubber grip that allows patients to self-inject without ever seeing the needle." Simpleject autoinjectors are available free to patients from their physicians, R.Ph.s, or by calling 1-(866) KINERET.

According to Schiff, the most common side effect of anakinra involves injection-site reactions, "These reactions are usually seen early, go away, and are not limiting to therapy; however, if they are present all the time or are getting bigger, patients should notify their physicians." Other concerns with therapy involve the potential risk of serious infections. In clinical trials, the incidence of serious infections requiring hospitalization was 2% with anakinra, compared with less than 1% with methotrexate. Although anakinra should be discontinued if a patient develops an infection, therapy can usually be resumed once the infection has resolved.

Though anakinra is priced competitively with infliximab and etanercept, at nearly $1,000 per month, the cost for maintenance therapy is not cheap. For this reason, several community R.Ph.s echo the sentiment of Craig Housel, manager of the Palmyra Pharmacy in Palmyra, Pa., "I won't keep [anakinra] in stock until I have a call for it."

Expanding on the cost issue, Eric Boyce, Pharm.D., professor of clinical pharmacy, University of the Sciences in Philadelphia, said, "Although anakinra seems to be efficacious and have a reasonable level of safety, insurance companies may not cover it due to a lack of good pharmacoeconomic data, even though it appears easier to monitor and safer than drugs like methotrexate, leflunomide, and gold."

According to Boyce, it is simply too early to tell what the long-term effects of altering the immune system might be and whether patients will be at risk of developing serious infections or malignancies.

Kelly Dowhower Karpa, R.Ph., Ph.D.

The author is a clinical writer in Pennsylvania.

TIPS TO REMEMBER: Kineret

• Kineret is administered once daily by subcutaneous injection.

• Physicians should be notified if injection-site reactions are severe or persistent or if an infection develops.

• Kineret should be discontinued in patients who develop serious infections.

• Kineret should not be utilized concurrently with drugs that block activity of tumor necrosis factor alpha.

 

Kelly Karpa. Recombinant drug offers new option for aching joints. Drug Topics 2001;23:12.