FRI0212 ADALIMUMAB TREATMENT EFFECTS ON RADIOGRAPHIC PROGRESSION OF JOINT DISEASE IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS FROM ADEPT
P. J. Mease1, J. T. Sharp2, P. Ory3, D. D. Gladman4, C. T. Ritchlin5, E. H. Choy6, M. A. Weinberg

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OP0169 INFLIXIMAB INHIBITS PROGRESSION OF RADIOGRAPHIC DAMAGE IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: RESULTS FROM IMPACT 2 TRIAL
D. Van der Heijde, A. Kavanaugh, A. Beutler, C. Guzzo, B. Zhou4, L. Dooley, C. E. Antoni, G. G. Krueger, D. Gladman

The paradigm of disease modification in rheumatoid arthritis is one that has been embraced by rheumatologists with the demonstration that effective therapeutic strategies decrease rates of radiographic progression, measured as erosions and joint space narrowing. While sulfasalazine, leflunomide, and methotrexate have been shown to be effective in slowing progression, the combination of methotrexate with all available TNF antagonists, as well as with anakinra and abatacept, have now been shown to further decrease the rates of progression compared to methotrexate alone.

Psoriatic arthritis is increasingly recognized as a significant destructive process in many with erosive changes occurring rapidly in many patients. Studying the disease modifying potential of drugs in this disease process has required slight modification of the scoring methods used for RA to reflect the particular joint involvement and radiographic findings of PsA.

Etanercept has been shown to decrease the rates of radiographic progression in PsA (Mease et al Arthritis Rheum 2004; 50: 2264-2272). Two studies, FRI0212 and OP0169, were presented showing 2 additional TNF inhibitors to be effective at reducing radiographic progression in PsA.

In Poster FRI0212, the results of the ADEPT study for psoriatic arthritis demonstrated that Adalimumab 40 mg every other week was effective in decreasing radiographic progression. In this one year study of more than 300 patients with longstanding, moderately to severely active PsA, an initial 6 month placebo-controlled portion was followed by an open label roll over to active treatment. Plain XRays were performed at baseline, 6 months, and at 1 year over one year.

Significant differences were seen in progression between adalimumab and placebo at the six month time point, as noted in the table below.

The lack of progression was maintained over 1 year, with patients rolling over to active treatment demonstrating slowing of the rate noted in the first 6 month period.

Results from the IMPACT study of infliximab in psoriatic arthritis were presented at ACR 2004 (http://www.hopkins-arthritis.org/physician-corner/education/acr2004/psoriatic.html#1135) demonstrating that infliximab at 5 mg/kg given every 8 weeks inhibited radiographic progression in PsA.

Further data were presented here at Eular, abstract OP0169, from IMPACT2, a second placebo-controlled study of 200 Psoriatic arthritis patients using 5 mg/kg infliximab every 8 weeks after induction at 0, 2, and 6 weeks, with Xrays evaluated at baseline and 6 months.

Less radiographic progression, measured as erosions (p<0.001) or joint space narrowing (p=0.013) or the composite van der Heijde-Sharp score (-0.70 2.53 versus 0.82 2.62, p<0.001), was seen in the infliximab treated patients compared to placebo. However there was no difference between the groups in other psoriatic arthritis specific assessments including pencil in cup and osteolysis.

In this study only approximately 10% of patients progressed in the placebo group with only one patient showing progression in the infliximab treated group indicating that the a few patients with significant progression were driving mean changes.

Conclusions: These studies indicate that the TNF inhibitors, adalimumab and infliximab, can significantly inhibit radiographic disease progressionin in patients with psoriatic arthritis.

Editorial Comment: These studies confirm that radiographic progression in psoriatic arthritis is a modifiable endpoint using TNF antagonist therapy, an effect that can be demonstrated on a group level within 6 months. The fact that fewer patients progressed overall in these trials of Psoriatic arthritis than in RA clinical trials makes it even more important to determine, if possible the clinical, biochemical, and radiographic markers to identify the group of patients for whom the most aggressive treatment options are needed.

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