Adalimumab

Adalimumab, which contains only human peptide sequences, is a high-affinity monoclonal antibody to soluble and membrane-bound TNF-a.⁶¹ It also lyses surface TNF–expressing cells in vitro in the presence of complement.⁶¹ Adalimumab is not yet approved for use in psoriasis, but in investigations conducted to date of its use in psoriasis, it is administered in a stepped-dosing paradigm starting with a weekly dose of 80 mg SC for 1 or 2 doses followed by 40 mg SC either weekly or every other week (EOW).⁶¹ The package insert for the use of adalimumab in nonpsoriasis indications (ie, rheumatoid arthritis) states that there is a risk of serious infection with adalimumab and that testing for tuberculosis is required prior to treatment. The labeling also carries a warning about an increased risk of central nervous system (CNS) demyelinating disorders and lymphoma, and there have been rare cases of lupus-like syndrome in association with adalimumab treatment. Patients who develop a new infection or any signs of neurologic problems or lymphoma during treatment should be monitored closely and adalimumab discontinued if a serious condition is confirmed.⁶¹

Performance in short-term studies

• After 12 weeks of therapy in a double-blind clinical trial, PASI 75 was achieved by 80% of patients treated with 80 mg adalimumab at weeks 1 and 2 followed by 40 mg each week, 53% of those treated with 80 mg at week 0 followed by 40 mg EOW, and 4% of those treated with placebo. The rates of adverse events were similar in the adalimumab and placebo groups, and there were very few discontinuations due to adverse events.^62-64
• Patients who attained PASI 50 after 12 weeks of adalimumab therapy in a double-blind trial were allowed to continue in a 24-week extension to 36 weeks. An interim analysis of this ongoing study at 24 weeks showed that 72% of patients treated with 40 mg each week (Figure 12) and 64% treated with 40 mg EOW attained PASI 75 at week 24. In patients who received placebo for 12 weeks followed by 12 weeks of 40 mg adalimumab EOW, 55% of patients achieved PASI 75. Serious adverse events occurred in 6.7% of the 40 mg EOW dosing group and 10.0% in the 40 mg weekly group, versus 0.0% in the placebo/adalimumab crossover group. The specific nature of those serious adverse events has yet to be reported.^63,64




Figure 12

Other studies

• Psoriatic arthritis. The preliminary results from a study of the use of adalimumab in the treatment of psoriatic arthritis suggest that 66% of patients will achieve ACR 20 after 12 weeks of adalimumab therapy.⁶⁴ Improvements in target lesion response and PASI responses were also seen in these patients.⁶⁴

Snapshot of adalimumab
Adalimumab is an anti-TNF agent that appears to be highly effective in the treatment of psoriasis, but it has not yet been approved for the treatment of this condition. It appears that adalimumab may be as effective as infliximab in psoriatic disease but with a more convenient dosing regimen and less risk of dose-creep (which has not been reported during adalimumab therapy for rheumatoid arthritis). Like the other anti-TNF agents, etanercept and infliximab, adalimumab therapy has been associated with an increased risk of infection and may carry an increased risk for demyelinating disorders or congestive heart failure. These are problems that are associated with anti-TNF agents as a class, but it is not yet clear how, or if, adalimumab in particular affects the risk of certain serious conditions.

Future directions for adalimumab research
Very few studies have been done on the safety and efficacy of adalimumab in the treatment of psoriasis. Additional randomized controlled trials, long-term studies, and large-scale safety studies in psoriasis patients are needed. Studies should also be conducted to determine the duration of effect of adalimumab once treatment has been discontinued and how patients respond to re-treatment. As is true for all anti-TNF agents, the relationship between adalimumab and an increased risk of infectious, neurologic, cardiovascular, or other disorders needs to be more fully investigated.