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| John Flynn, M.D.
Treatment Clinical Outcomes | ||
| Treatment | ||
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Abstract 446: Evidence for Infliximab-induced improvement in bone metabolism in psoriatic arthritis Background: Patients with psoriatic arthritis may develop damage to the bone as a result of the arthritis causing erosions. This bone activity is felt to be indicated by the presence of specific markers of bone metabolism. This has been demonstrated in the past in psoriatic arthritis patients when compared to patients without arthritis. In this multicenter, double-blind, randomized controlled trial (IMPACT-2), they wanted to see if there is a difference in these bone markers between the treated group (Infliximab) and the placebo group. Methods: Two-hundred patients with polyarticular psoriatic arthritis were randomized either to receive placebo or Infliximab infusions (5 mg/kg) at weeks 0, 2, 6, 14, and 22. Along with other parameters of disease, several markers of new bone formation were followed including: osteocalcin (OC) and bone alkaline phosphatase (BAP). Also checked were markers for bone loss or resorption; these were C-terminal telopeptide and N-terminal telopeptide (NTX and CTX). Results: The baseline measurements of all these bone parameters were similar prior to starting therapy. There was an increase from baseline in osteocalcin in the treated group (9.2% at week-2, 17.4% at week-14). BAP levels remained unchanged in both groups. CTX levels were consistently elevated in the placebo group. NTX remained constant in the Infliximab group, but did increase in the placebo group. Conclusion: There is a rapid change in the osteocalcin levels as well as the CTX levels in the treated group as early as two weeks following a single infusion. This indicates an effect of this treatment intervention on these two markers for bone change. Editorial Comment: This is very interesting data that helps us look closer at what is happening with inflammation at the level of the bone. We know that psoriatic arthritis leads to erosions and a goal of any form of therapy would be to prevent such damage. This indicates, as a result of the TNF inhibitor, osteocalcin (a marker of bone formation) is increased and CTX (a marker of bone breakdown) is suppressed. These may be biomarkers that can be used in the future to follow the activity of disease. | ||
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Abstract 1135: The Infliximab multinational psoriatic arthritis controlled trial (IMPACT): Results of radiographic analysis after one year Background: This study analyzes data from the IMPACT trial to determine the effect of Infliximab on the progression of structural bone damage in patients with psoriatic arthritis. In this study, there were two groups. One group was treated with Infliximab at 5.0 mg/kg on a scheduled basis through 50 weeks. The second group was started on placebo and then switched to Infliximab at week-16 and continuing that through 50 weeks of therapy. In both groups, x-rays of the hands and feet were obtained at the beginning of the study and then at the end of the study, 50 weeks later. These x-rays were scored using a standardized process (modified vdH-Sharp). Results: Radiographs at baseline and then at the end of the study were available on 72 patients that participated in this study. Prior to this study, patients had been found to have an annual progression rate of 5.8 units/year. During this study, the placebo/Infliximab group progressed 0.05 units and the Infliximab group showed improvement in their score by 1.52 units. The bone erosion score improved 0.4 units in the placebo group and 0.98 units in the treatment group. At the end of the study, 84% of the patients in the treatment group and 82% in the placebo group had no worsening in their total radiographic score. Conclusion: Based on evaluation of these patients prior to entry into the study, it was predicted that they would continue to progress at the previous level of 5.8 units/year. This rate of progression was markedly altered by administration of Infliximab. Editorial Comment: This is an exciting development in patients with psoriatic arthritis and is consistent with studies looking at TNF inhibitors in the treatment of rheumatoid arthritis showing delayed progression of radiographic changes. This occurred as well in the placebo group that received Infliximab therapy only after observation for a full four months. It will be important to continue to follow these patients to see if this change in the rate of progression persists over time. | ||
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Abstract 1622: Adalimumab efficacy and safety results in patients with moderate to severe chronic plaque psoriasis with and without psoriatic arthritis Background: This study was conducted to learn the effect of adalimumab in patients with cutaneous psoriasis, both with and without joint disease. Methods: In this study conducted by dermatologists, patients with severe chronic plaque psoriasis both with and without arthritis were studied in a randomized, double-blind, placebo-controlled fashion using adalimumab injections twice a month. Patients who had psoriasis affecting over 5% of their body surface area were enrolled in this trial. The researchers compared two different doses of adalimumab with placebo. These patients were then evaluated for improvement of their skin. Patients were analyzed based on whether they had psoriatic arthritis or not. A specific outcome of skin improvement, known as the PASI-75 Response, was used as the primary outcome of efficacy. Results: This study showed that the skin improved in patients with and without psoriatic arthritis. There is a tendency for the skin to get better more quickly with the higher dose of adalimumab. In this short-term study, there was no increase in adverse events in the treatment groups versus the placebo groups. Editorial Comments: This study demonstrates that the presence of arthritis does not have a deleterious effect on the response of patients skin disease to TNF inhibitors. | ||
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Abstract 1635: Infliximab improves psoriasis regardless of arthritis response in patients with active psoriatic arthritis: Results from the IMPACT-2 trial Background: This is an analysis of the IMPACT-2 trial in which 200 patients with psoriatic arthritis were evaluated to determine the effect of Infliximab. Results: Two groups (Infliximab versus placebo) were studied for 14 weeks with the Infliximab group demonstrating significant improvement in their arthritis (ACR-20 58% versus 11%) and skin disease (PASI-75 64% versus 2%). When evaluating the group of treated patients who responded by achieving ACR-20 (58%) versus those who did not respond (42%), there was a significant improvement in the skin disease in both sets (PASI-75 of 87% versus 74% at week 14). Conclusion: While Infliximab improved the joint symptoms in the majority of patients with active psoriatic arthritis, it also had significant effect on the skin disease in patients regardless of the improvement of their joint disease. Editorial Comments: While TNF therapy can be effective for both the skin and the joints, it is important to note that one may be more responsive than the other to therapy. This is a challenge that requires very careful evaluation of both the skin and joints and a close working relationship between the rheumatologist and dermatologist. This will require further evaluation to see if combinations of therapies may be used to achieve maximum outcomes in both conditions. | ||
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Abstract 1637: Infliximab significantly improves joint and skin involvement in psoriatic arthritis to a substantial extent and irrespective of baseline joint involvement where methotrexate is used: Analysis of clinical response from the IMPACT-2 trial Background: This study is an analysis of the IMPACT-2 trial with measurement of more stringent outcomes for both joint and skin improvement. It also looks at baseline disease characteristics to see if they predict outcome. Results: In looking at 200 patients with psoriatic arthritis, it was determined that 15% of the treated patients achieved the more stringent outcome of ACR-70 compared to only 1% of placebo treated patients. Forty-one percent of treated patients achieved a PASI-90 compared to no patients in the placebo group at 14 weeks of therapy. The ACR-70 increased to 27% at 24 weeks. The response to therapy was similar among patients, whether they were using methotrexate or not. The response was also consistent among various degrees of baseline joint involvement as determined by joint count. Conclusion: This therapy appears to be just as effective in those patients using methotrexate versus those not. Also, the number of swollen joints does not adversely affect the improvement that can be seen with this intervention. Editorial Comments: It has been long appreciated that psoriatic arthritis can have a number of different joint presentations (i.e., oligoarticular versus polyarticular). This study suggests that presentation does not alter the benefit that can be seen with this form of therapy. Also, the concomitant use of methotrexate does not appear to alter efficacy of this therapeutic intervention. | ||
| Clinical Outcomes | ||
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Abstract 447: Two Danish national twin studies on psoriatic arthritis Background: There has always been a question of the influence of genetics in psoriatic arthritis. This is not as well-established as it is in other B27-related diseases such as ankylosing spondylitis. Using nationwide twin cohort studies that have been established in Denmark, this question was addressed. Methods: Since 1920, Denmark has established three separate registries of all twin individuals born in that country. They then surveyed twins with a questionnaire to determine if they had been diagnosed with psoriatic arthritis. All those that answered affirmatively were invited to participate in a physical examination to assess the presence of this condition. Results: Over 50,000 twin individuals were surveyed. A total of 228 individuals reported the diagnosis of psoriatic arthritis. One-hundred-eighty-four of these individuals agreed to a physical examination. Out of these, 49 had the diagnosis of psoriatic arthritis confirmed. Of these 49 individuals, there existed 35 paired siblings with 1 of 10 identical twins (monozygotic) and 2 of 25 fraternal twins (dizygotic) both having psoriatic arthritis. Statistical analysis of these rates indicates there is not a genetic effect in the etiology of psoriatic arthritis in this cohort. Comments: This study provides a very interesting look at large nationwide cohorts of twins that exist in Denmark. This suggests that there is not a genetic predilection in the development of psoriatic arthritis. It is currently our practice not to do any genetic studies on patients with psoriatic arthritis for clinical purposes alone. | ||
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