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Psoriatic arthritis (PsA) used to be considered a mild disease, but the development of erosive and deforming arthritis has been shown in a large proportion of patients.1
Disease modifying antirheumatic drugs (DMARDs) often do not achieve a satisfactory control of articular symptoms and there is no evidence of their effect on the progression of joint damage.2 Tumour necrosis factor α (TNFα) has a role in the pathogenesis of PsA,3 and there are some encouraging reports about the efficacy of TNFα neutralising agents for the treatment of the spondyloarthropathies, including PsA.4–8
METHODS AND RESULTS
We evaluated in an open label, six month pilot study the safety and efficacy of infliximab in association with methotrexate (MTX) in 12 patients with PsA resistant to conventional DMARD treatment.
Patients were considered eligible for the study if they fulfilled all of the following criteria: (a) diagnosis of psoriasis confirmed by a dermatologist; (b) diagnosis of spondyloarthropathy according to the European Spondyloarthropathy Study Group criteria9; (c) active disease despite treatment with MTX + steroids + non-steroidal anti-inflammatory drugs (NSAIDs); active disease was defined as the presence of at least one swollen joint, active tendonitis or dactylitis in one tendon or finger, and/or inflammatory spinal pain.5
Four men and eight women were enrolled, with a mean (SD) age of 48.4 (13.6) years, a mean duration of cutaneous disease of 15.5 (10.5) years, and a mean duration of articular symptoms of 8.6 (5.6) years. Eleven patients had a polyarthritis with prevalent peripheral arthritis and only one patient had a predominantly axial disease.
All the patients had been treated with MTX to which they did not respond and seven patients had also been unresponsive to combination therapy (MTX plus sulfasalazine and/or cyclosporin). Five patients required steroid treatment at baseline (prednisone ⩾5 mg daily). Treatment with MTX was maintained throughout the study at the dose and schedule regimen used in the two months before inclusion in the study (15 mg/week for nine patients, 10 mg/week for three). Steroids and NSAIDs were allowed during the study, provided that the doses did not exceed those used at the study entrance. DMARDs other than MTX had to be discontinued at least two months before entrance to the study.
Infliximab at a dose of 5 mg/kg was given at weeks 0 (baseline), 2, 6, 14, and 22. The following outcome measures of disease activity were evaluated at weeks 0 (baseline), 2, 6, 10, 14, 22, and 26: patient global health status, pain, and disease activity; Health Assessment Questionnaire; doctor global disease activity; tender and swollen joint count; psoriasis activity skin index; erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) (table 1). The American College of Rheumatology (ACR) improvement criteria for rheumatoid arthritis with 20%, 50%, and 70% improvement were also assessed.
At week 10 a significant decrease (p⩽0.01) was seen for all variables with the exception of the tender joint count, ESR, and CRP. At week 26 this decrease was even stronger for many variables and a significant decrease was seen also for the tender joint count and CRP as compared with baseline values.
At week 10 six patients met the ACR20 criteria for improvement; five of them also met the ACR50, three the ACR70. At week 26 10 patients met the ACR20 criteria (all the patients still receiving treatment with infliximab); six of them also met the ACR50, four the ACR70. At week 26 only two patients still required steroid treatment, both of them at a lower dose than at the study entrance.
Infliximab was well tolerated in all patients and we did not see any infusion reaction or delayed hypersensitivity reaction. Two patients were withdrawn from the study because of the occurrence of serious events. One patient was admitted to hospital for angina pectoris after the third infusion and we decided to stop the study treatment. Another patient withdrew from the study after the fourth infusion when a pulmonary malignancy occurred. In both of these cases it is unlikely that there was a correlation between the adverse event and the study treatment, especially as the treatment was short.
Our data confirm the efficacy of infliximab in patients with PsA, suggesting that it may be the preferred treatment for patients resistant to conventional DMARDs.
In other reports the efficacy of treatment with anti-TNFα agents on PsA was less pronounced4,8 than in our study. This may be due to several factors, including the selection of the patients (11 of our 12 patients had a peripheral polyarthritis) and the therapeutic regimen (the association of MTX with infliximab might have enhanced its therapeutic effect). The maximum effect of this treatment on articular symptoms may not be apparent after the loading dose regimen of three infusions, but seen later on. Controlled studies and longer follow up are needed to optimise the selection of patients who can benefit from this form of treatment.