While no remission criteria have been standardized for PsA, data from several clinical series20
and from the British Society for Rheumatology Biologics Register23
reported a frequency of clinical remission ranging from 17.6% to 58%, with the highest rate observed in patients treated with anti-TNFα agents. This wide range may be partly explained by the absence of validated criteria for remission in PsA, which has led to the use of different sets for remission assessment, as well as the different methods of selecting patients. In a previous study,16
we evaluated the frequency and duration of clinical remission in patients with early peripheral PsA requiring second-line drugs, adopting a restrictive set of criteria based on the absence of systemic manifestations, peripheral and axial articular symptoms (including tendons and entheses), extra-articular features, and normality of acute-phase reactants. The overall frequency of remission was 24.1%, with a remission rate of 60.5% in patients taking anti-TNFα agents. In this study, a consistent percentage of subjects with PsA, treated with either traditional disease modifying anti-rheumatic drugs or anti-TNF, did not relapse over a prolonged time (mean 12 ± 2 months) after therapy interruption, thus suggesting an intermittent therapeutic strategy as a possible option for PsA patients achieving remission.
Since the recruitment period in the above-mentioned study preceded the approval of ADA for the treatment of PsA, none of the patients received this drug. However, the effectiveness of ADA for PsA therapy has been demonstrated in different clinical trials,7
with approximately 60% of patients achieving a good clinical response. In addition, a recent study of 152 PsA patients with long-standing disease (median 8 years) treated with ADA demonstrated a 58% remission rate, with a significant difference with respect to the 48% rate recorded in patients with RA.22
Given the evidence of the efficacy of ADA (and of all anti-TNF agents in general terms) in the treatment of PsA, another important issue is the economic impact of this therapy, which has an estimated cost of around €14,000/patient/year. Consequently, every effort to reduce this economic burden is desirable on the condition that patient outcome and quality of life does not worsen. As we observed in a previous clinical series,16
in PsA patients achieving remission, therapy withdrawal may be a possible strategy for reducing drug-exposure risk and lowering the economic burden on public health care systems. This therapeutic approach has also been attempted in patients with RA. In a Japanese study, 52 (30.2%) of the 172 RA patients treated with combined infliximab and MTX achieved remission. In nine of these patients, infliximab was discontinued with no recurrences over a mean follow-up period of 14.2 months.29
In this context, we designed the present case-control study to evaluate the efficacy of ADA dose reduction in PsA patients achieving clinical remission. Over a 3-year period, according to the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis recommendations,3
we treated 76 patients with active early PsA and 55 RA patients with ADA. Confirming the results of other authors,22
in our study, a significantly higher percentage of PsA patients compared with those with RA achieved clinical remission (69.7% vs 30.9%; P
= 0.019). After ADA dose reduction to 40 mg every 4 weeks, 47 of the 53 (88.6%) PsA patients maintained remission over a mean follow-up period of 28.9 ± 8.4 months compared with three of the 17 (17.6%) RA patients (P
< 0.001); no significant worsening of skin manifestations were found.
To the best of our knowledge, this is the first study on PsA patients that demonstrates the sustained efficacy of ADA in maintaining remission after halving the dose. A similar therapeutic strategy has been previously attempted both in RA and in ankylosing spondylitis patients. In an open-label study of 21 RA patients, infliximab dose titration using disease activity score improvement allowed for the reduction of 67% of the total amount of the drug with maintenance of clinical response.30
The sustained efficacy after halving the dose of etanercept in patients with ankylosing spondylitis has been reported in two studies. In the first, 18 patients receiving etanercept at a dose of 25 mg/weekly were still in remission after 6 months,31
and in the second, 16 patients maintained remission after etanercept tailoring over a mean follow-up period of 26.1 ± 21 months.32
The successful ADA dose halving in our PsA patients suggests two main considerations. First, none of the patients included into the present study experienced ADA-related adverse events, allowing us to speculate that dose reduction may be hypothetically associated with a long-term lower incidence of drug-related adverse events and toxicity. Second, ADA dose halving permitted a marked cost-saving effect, with an estimated savings of more than €700,000 (cost of ADA standard dose therapy/patient/month: €1166; ADA halving dose: €583 /month; multiplied by 47 patients over a mean follow-up period of 28 months).
To conclude, our results indicate that clinical remission is possible in a high percentage of patients with early PsA receiving ADA, with a significant difference with respect to those with RA. Moreover, different from patients with RA, after ADA dose reduction, a high proportion of PsA patients (88.6%) maintained remission over a long-term follow-up period. Sustained disease remission after ADA dose halving suggests the application of this therapeutic strategy in clinical practice with important advantages in terms of drug-exposure risk and cost savings.