Making the appropriate choice ... requires having a clear understanding of the benefits and disadvantages of each drug.
The determinants are both medical and practical, according to Dr. Abramovits. Making the appropriate choice also requires having a clear understanding of the benefits and disadvantages of each drug.
"Aside from seeking the highest benefit in terms of PASI reduction," he says, "I look at whether the patient has inflammatory arthritis. If so, that leads to the choice of a drug that reduces TNF alpha. I also look at risk factors and contraindications. A patient with multiple sclerosis, for example, cannot be placed on a drug with toxicities that might aggravate it. Once we get beyond those issues, I look at what is most economical and practical for the patient."
He says, "I selected very well-controlled studies that allowed me to compare efficacy over similar timelines. We have data for 12 and 24 weeks. Next year, I'll also have it for 48 to 52 weeks."
Conclusions As immunosuppressive agents, all five drugs carry the risk of serious infections and malignancy. Baseline and periodic tests help in assessing the risk for infection, lymphopenia, thrombocytopenia, cancer, autoimmunity and other toxicities. Patients should avoid live vaccines and other immunosuppresents, if possible.
Infliximab has the highest response rate at 10 weeks (the endpoint in its studies, rather than the 12 weeks used in other drug trials), but it requires in-office IV infusions. The drug carries a warning for tuberculosis and should not be administered to patients at risk for congestive heart failure. The drug causes autoantibodies to develop; hence, escalating doses or concomitant use of methotrexate may be required. Other concerns: demyelinating disorders and hepatotoxicity.
Adalimumab has the fastest onset of improvement and is the second only to infliximab in reducing the severity of psoriasis. It is self administered via subcutaneous dosing weekly or every other week. Patients on adalimumab are at risk for contracting tuberculosis.
Efalizumab and etanercept, which are also administered subcutaneously, have response rates at 24 weeks and onset at two weeks to four weeks. Efalizumab is dosed weekly and etanercept twice weekly for three months and then weekly thereafter. Due to frequent flu-like reactions to the first dose, treatment should be launched with a conditioning dose. Physicians need to warn patients of possible flares during and following treatment and of thrombocytopenia. Patients using etanercept are at increased risk for TB, congestive heart failure and demyelinating disorders.
Alefacept requires office visits for IM injections once a week for 12 weeks. Some patients may require two courses of therapy before significant benefits are noted. Mean duration of response is seven months. Due to the risk of lymphopenia, blood counts are necessary weekly or every-other-week. Cost and hepatotoxicity are other considerations. Advantages: patients may enjoy 12 weeks or longer of drug-free benefits between repeated courses; no increased risk of infections or malignancies have been noted to date.
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