Subjects were recruited from 50 sites located in North America and Europe between March 2003 and April 2004. Adult patients with moderately to severely active psoriatic arthritis (at least 3 swollen and 3 tender joints) were randomized to receive adalimumab, 40 mg injected subcutaneously every other week, or placebo injection in addition to background methotrexate (if already prescribed and stable for 4 weeks prior to enrollment). Stable doses of NSAIDs and prednisone at or below 10 mg per day were allowed. Subjects with any prior exposure to TNF inhibitors were excluded. Subjects were stratified at randomization based on current methotrexate use and extent of skin involvement by psoriasis (< 3% body surface area or >3% body surface area).
Subjects were followed for 24 weeks. The primary efficacy endpoints were the proportion of ACR20 responders in the adalimumab treated group vs. the placebo group at after 12 weeks of treatment, and radiographic progression of disease at 24 weeks. Radiographs of the hands and feet were scored according to a modified Sharp scoring method taking into account joint groups affected by psoriatic arthritis (i.e. DIP joints) and other characteristic radiographic features (i.e. osteolysis, pencil-in-cup deformities). Secondary efficacy outcomes included the ACR 50/70 responses at 12 weeks and the ACR 20/50/70 responses at 24 weeks. Psoriasis Area and Severity Index (PASI) Scores were used to evaluate efficacy in treating skin psoriasis in the subset of subjects with > 3% skin involvement at baseline.
315 subjects were randomized; 162 to receive placebo and 153 to receive adalimumab. Mean age of study subjects was 49 years, with just over half of subjects being male. Subjects were predominately Caucasian race (> 90% in both groups). On average, subjects had been diagnosed with psoriatic arthritis for 9 10 years, but had had psoriasis for approximately 17 years. Most subjects had symmetric polyarthritis, with only 1 subject each (in the adalimumab treated group) classified as having arthritis mutilans or axial spondylitis. As per a priori stratification, 50% of subjects were receiving concomitant methotrexate. Baseline characteristics were balanced between the adalimumab and placebo treated subjects. 149 subjects in the placebo treated group and 140 subjects in the adalimumab treated group completed the 24 weeks of the study.
Efficacy for Signs and Symptoms
|After 12 weeks of treatment
|After 24 weeks of treatment
|*results expressed as percent of subjects achieving level of response
Efficacy results were similar whether or not subjects were receiving background methotrexate.
Efficacy for Radiographic Progression Joint space narrowing and erosion scores were significantly different between adalimumab and placebo treated subjects, with mean change in modified Sharp scores of 1.0 in the placebo group compared with -0.02 in the adalimumab treated group (p<0.001) after 24 weeks of treatment.
Efficacy in Skin Psoriasis Mean PASI75 responses (reduction in extent of psoriasis by 75% or greater) were significantly greater in the adalimumab treated group compared to the placebo treated group after 24 weeks of therapy (59% vs. 1%, respectively; p<0.001) among the subset of subjects with > 3% skin involvement at enrollment.
Safety Serious adverse events were uncommon and were balanced between the two groups. A case of viral meningitis attributed to West Nile virus was reported in an adalimumab treated patient, but no cases of serious bacterial or opportunistic infections were reported over the 24 week study interval.
Adalimumab is effective in reducing the symptoms of psoriatic arthritis, retarding radiographic progression, and reducing skin involvement from psoriasis when used as monotherapy or in combination with methotrexate.
Based largely on the results of this study (known as ADEPT – Adalimumab Effectiveness in Psoriatic Arthritis Trial) adalimumab was approved by the FDA for the treatment of moderately to severely active psoriatic arthritis in October 2005. Thus, all three commercially available TNF inhibitors have received FDA approval for this indication. However, as with the TNF inhibitors in the treatment of rheumatoid arthritis, no head-to-head studies have been performed to evaluate comparative efficacy among the three agents. Therefore, no evidence-based recommendations can be made as to which TNF inhibitor should be recommended as first choice among this class. Even if tested head-to-head, there may not be a clear-cut efficacy advantage of any one of the TNF inhibitors over the other two. Even so, some patients may not respond as well to one agent as to another, but may benefit from switching to an alternate TNF inhibitor. Likewise, no published data is available on the effectiveness of switching to an alternate TNF inhibitor in the case of inadequate response.
It should be pointed out that, although used extensively for the treatment of psoriatic arthritis, methotrexate has never been evaluated with the same rigor that the TNF inhibitors are now being evaluated in this disease. Indeed, methotrexate may unfairly appear weaker in comparison since the earlier investigations utilized doses that would be considered less likely to be effective today (5 and 7.5 mg per week) due to safety concerns of the time which have largely proved to be unfounded. Caution should also be taken in evaluating the efficacy of methotrexate in trials such as this one, in which selection bias will make methotrexate falsely appear to be comparatively ineffective (since any number of uncounted subjects in which methotrexate has adequately controlled their disease would never be included). Due to issues of cost and minor but lingering uncertainties regarding long-term safety issues with the TNF inhibitors, good clinical practice would still mandate a trial of aggressively titrated methotrexate before initiating a TNF inhibitor in most patients with psoriatic arthritis.