Infliximab

Infliximab is a chimeric (approximately 30% murine, 70% human) monoclonal antibody that binds to both soluble and membrane-bound TNF-a.⁵³ There is also evidence that infliximab can cause apoptosis of cells expressing transmembrane TNF-a.^53,54 Infliximab is not yet approved for use in the treatment of psoriasis, but in clinical studies conducted in psoriasis patients, 3 or 5 mg/kg infliximab is administered as a 2-hour IV infusion at weeks 0, 2, and 6.⁵⁵ Neutralizing antibodies to infliximab can develop as a result of treatment, creating the need for larger or more frequent doses in the future (dose creep) or rendering the patient unresponsive to future infliximab therapy. The package insert for the use of infliximab in other disorders (ie, rheumatoid arthritis and Crohn’s disease) states that methotrexate should be administered along with infliximab to prevent the development of neutralizing antibodies. The package insert indicates that the most common adverse events with infliximab are infusion reactions, which occur in 22% of patients.⁵³ Most infusion reactions are minor, but serious reactions (including anaphylactic shock) have occurred, and any physician offering infliximab therapy must have the staff and facilities available to deal with this contingency. There is also a risk of serious infection with infliximab, and testing for tuberculosis is required prior to treatment.⁵³ Infliximab should be used with caution in patients with heart failure and discontinued if patients develop new or worsening symptoms. It should also be used with caution in patients with preexisting or recent onset of central nervous system (CNS) demyelinating disorders and discontinued if symptoms worsen or new symptoms appear. The labeling also carries a warning about an increased risk of lymphoma and lupus-like syndrome. Any signs of these conditions should be evaluated thoroughly and treatment discontinued if a serious condition is confirmed.⁵³

Performance in short-term studies

• At week 10 in a double-blind study of infliximab in psoriasis, 72% of patients treated with 3 mg/kg infliximab and 88% of patients treated with 5 mg/kg infliximab achieved PASI 75; by week 26, 14% of patients treated with 3 mg/kg infliximab were still at PASI 75 (Figure 11).⁵⁵ The most common adverse events were headache, pruritus, fatigue, and myalgia, with an incidence similar to placebo. Infusion reactions occurred in 15.7% of patients treated with infliximab and 2% of patients treated with placebo.⁵⁵




Figure 11

Performance in patient subpopulations

• The safety and efficacy of infliximab was consistent across all subgroup analyses (including gender, age, baseline PASI, body mass index, body surface area affected by psoriasis, and history of previous systemic psoriasis therapy), with 69% to 87% of patients achieving PASI 75 in the different subgroups.⁵⁶ At 10 weeks, the percentage of patients with both psoriasis and psoriatic arthritis who reached PASI 75 was approximately 75% in the 3 mg/kg infliximab group and approximately 88% in the 5 mg/kg group. These patients also showed improvements in Physician’s Global Response and DLQI scores.⁵⁷
• A small, open-label study evaluated the effects of 3 to 5 mg/kg infliximab in 11 patients with severe psoriasis that was refractory to several other systemic agents. Six weeks after the start of infliximab therapy, 64% of these patients had achieved PASI 75.⁵⁸

Other studies

• Psoriatic arthritis. In a double-blind study⁵⁹ of patients with psoriatic arthritis treated with 5 mg/kg infliximab, the percentage of patients achieving an ACR 20 was 58% at week 14 and 54% at week 24. In the placebo group, 11% and 16% of patients reached ACR 20 at week 14 and week 24, respectively.⁵⁹

Snapshot of infliximab
Infliximab is an anti-TNF agent that blocks the action of TNF and can kill cells expressing transmembrane TNF. Clinical studies suggest that it is highly effective against both psoriasis and psoriatic arthritis, but it is not yet approved for the treatment of either of these conditions. In clinical studies of its use in psoriasis, the onset of effect is very rapid and most patients see a dramatic improvement in their disease within 10 weeks of their first treatment. The most common adverse effects are infusion reactions, which occur in almost a quarter of infliximab- treated patients, although serious infusion reactions are uncommon. There are no long-term studies of the use of infliximab in psoriasis patients, but, like etanercept, infliximab does have a long history of safe use in the treatment of other inflammatory disorders. Infliximab is also associated with the same risks of infection and the same possible association with demyelinating disorders, lymphoma, and congestive heart failure that have been suggested for etanercept. There have also been a few cases of lupus-like syndrome and other unusual disorders during treatment with infliximab, but their relationship to infliximab treatment is unclear. The impressive efficacy of infliximab makes it an attractive treatment option for some psoriasis patients, but the need for IV infusion of this drug and facilities and personnel to manage any infusion reactions that may occur creates significant barriers to the widespread use of infliximab in psoriasis patients.

Future directions for infliximab research
Very few studies have been done on the safety and efficacy of infliximab in the treatment of psoriasis. Additional double-blind studies are needed, as well as long-term clinical trials and studies to examine the optimal dosing of infliximab in psoriasis patients. Dose-creep seems to be a common and significant problem when infliximab is used in the treatment of other disorders, and this phenomenon should be more fully evaluated in the treatment of psoriasis. More studies are also needed on how best to predict, prevent, and manage infusion reactions during infliximab administration. There have been reports that prophylaxis with diphenhydramine and acetaminophen can decrease the risk of infusion reactions,⁶⁰ but further study is warranted. As is true for etanercept, the relationship between infliximab therapy and a variety of rare but potentially serious conditions must be more fully investigated. Consequently, all serious problems that occur during infliximab therapy should be carefully documented and reported to the manufacturer and to MedWatch.