CHICAGO - Adalimumab was well tolerated, with a low incidence of adverse events and serious infections, in two studies totaling almost 1,800 patients who took the drug for up to 5 years.
The first study was a meta-analysis of 11 global clinical trials, totaling almost 1,721 patients. All of the phase II or III studies included safety data analyzed in 2007 and 2008, according to a report by Dr. Richard Langley and his associates presented at the summer meeting of the American Academy of Dermatology.
The drug was administered subcutaneously in all treatment groups. Dosing regimens included 80 mg/week initially, followed by 40 mg every other week (1,039 patients were on this regimen); 40 mg every other week (422 were on this regimen); 80 mg for the first 2 weeks, followed by 40 mg every other week (198 patients were on this regimen); and 80 mg every other week (62 patients).
All patients were about 44 years old, with disease duration of 18 years. The percentage of body involved was 27%; psoriatic arthritis was present in 28%, according to Dr. Langley of Dalhousie University, Halifax.
The length of adalimumab exposure ranged from 48 weeks to 5.5 years; the mean exposure time was 2 years. At both the 2007 and 2008 safety analyses, the overall rate of adverse events was 3 events per person-year.
The most commonly reported were nasopharyngitis, upper respiratory infection, and sinusitis, which accounted for 47% of the 3,489 infectious adverse events (AEs) reported.
In the 2008 analysis, 60 serious AEs were reported in 50 patients. There were two occurrences of sepsis; the incidence rates of pneumonia were 0.002 per person-year; limb abscess occurred at a rate of 0.001 abscess per person-year; and other serious infections, less than 0.001 per person-year.
Tuberculin skin tests were positive in 138 patients in the 6% of patients who received a test at baseline. There were no cases of latent TB reactivation in those who complied with prophylactic treatment. Six patients developed tuberculosis; four of them were Asian males.
Twelve opportunistic infections occurred in 11 patients; none was considered serious. The infections included 11 cases of candidiasis and 1 case of coccidioidomycosis, which occurred in the southwestern United States where the disease is endemic.
The second study examined efficacy and adverse event rates in patients who took adalimumab for moderate-severe plaque psoriasis of the hands and feet. These 72 patients were included in a single 28-week randomized, placebo-controlled crossover trial.
The patients' mean age was 50 years. The duration of psoriasis was about 12 years; the duration of hand/feet psoriasis, about 8 years.
The crossover trial randomized 49 patients to 40 mg adalimumab every other week and 23 to placebo for 16 weeks; after that, an open-label extension trial included all patients taking 30 mg every other week.
At week 16, significantly more of the adalimumab-treated patients reported being clear or almost clear of their plaque lesions, compared with placebo (31% vs. 4%). At weeks 16 and 28 of the trial, 51% of the active group and 47% of the crossover group reported scores of clear or almost clear.
During the first 16 weeks, adverse events occurred in 63% of the active group and 70% of the placebo group. Serious adverse events occurred in none of the active group and 4% of the placebo group. Infectious AEs occurred in 35% of the active group and 44% of the placebo group. One malignancy occurred in the placebo group.
There was one opportunistic infection in the active group. Hepatic events occurred in one patient in the adalimumab group.
During the crossover phase, AEs occurred in 43% of the adalimumab group and 39% of the crossover group; the most commonly reported were nasopharyngitis, headache, diarrhea, and infection site reaction.
AEs were considered serious in two adalimumab patients. Infectious adverse events occurred in 24% of the adalimumab group and 17% of the crossover group. There was one case of heart failure in the adalimumab group.
Three adalimumab patients and two crossover patients discontinued treatment because of the AEs. There were no deaths, serious infections, cases of tuberculosis, demyelinating diseases, lupus-like syndromes, lymphomas, or non-melanoma skins cancers reported.
Disclosures: All of the studies were supported by Abbott Laboratories. Dr. Langley disclosed financial relationships with Abbott, Amgen, Bristol-Myers Squibb, Celgene, Centocor, Isotechnika, LEO Pharma, NanoBio, Novartis, Pfizer, Schering, and Serono.