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| John Flynn, M.D.
Psoriatic Arthritis and Psoriasis | ||||||||||||
| Ankylosing Spondylitis | ||||||||||||
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Abstract 518 Inhibition of Radiographic Progression in Ankylosing Spondylitis (AS) by Continuous Use of NSAIDs NSAIDs remain first line therapy for AS and are associated with rapid improvement in axial signs and symptoms. The potential for this class of drugs to modify/slow disease has never been shown, though few rigorous evaluations have been performed. Here, Wanders et al hypothesize that continuous use of NSAIDs will reduce progression of structural damage in AS compared to intermittent, on-demand use. Methods: This was a two-year treatment study in which subjects fulfilling modified New York criteria for AS were randomized into one of two treatment groups. Group 1 (continuous NSAID use) was assigned to receive celecoxib 100 mg BID. The dosage could be increased to 200 mg BID or an alternative NSAID could be used for severe symptoms. Group 2 (on-demand use) was assigned to receive celecoxib per patient demand for symptoms. A change to an alternate NSAID was allowed for severe symptoms. Participants underwent lateral plain radiographs of the cervical and lumbar spine at baseline and after two years. Radiographs were scored using the modified Stoke Ankylosing Spondylitis Spine Score (SASSS) by a blinded observer. The primary endpoint was change in SASSS at two years. Results: 215 patients were randomized, 111 into the continuous NSAID group and 104 into the on-demand NSAID group. Mean age in both groups was approximately 40 years. 70% were male. 80% were HLA B-27 positive. Groups were well matched to baseline characteristics, except for disease activity, which was slightly higher in the on-demand NSAID group. 96 participants in the continuous NSAID group completed the study. At two years, 68 were using celecoxib while 28 had changed to an alternate NSAID. The average dose of celecoxib in this group was 243 mg/day. 86 participants in the on-demand NSAID group completed the study. At two years, 67 were using celecoxib while 19 had changed to an alternate NSAID. The average dose of celecoxib in this group was 201 mg/day. Efficacy Endpoints - For subjects with complete radiographs (n=76 in the continuous NSAID group, n=74 in the on-demand NSAID group), the mean change in SASSS was 0.4 and 1.5 for the continuous NSAID and on-demand NSAID groups, respectively. BASDAI scores were similar in both groups over two years. Safety Endpoint - GI symptoms were equivalent in both groups. Hypertension was higher in the continuous NSAID group. Conclusions: Continuous NSAID use in AS is superior to intermittent, on-demand NSAID use in slowing radiographic progression over two years. Continuous NSAID is as safe as intermittent NSAID. Editorial Comments: These results are quite surprising since most rheumatologists have assumed that NSAIDs do not slow progression of any inflammatory joint disease. Well designed treatment and radiologic studies of NSAIDs or most DMARDs in AS have been few and far between. However, the current findings are even more surprising given that the mean doses of celecoxib taken by the two groups are only modestly different. Cox-2 has been shown to regulate differentiation of mesenchymal cells to osteoblasts. Thus, slowing syndesmophyte formation via Cox-2 inhibition with NSAIDs is the proposed mechanism of action. A critical question, as in RA, is whether these radiographic differences in progression will be associated, in the long-term, with better functional and quality-of-life outcomes. It is unlikely that monotherapy with an NSAID or Cox-2 inhibitor (without concurrent DMARD therapy) will be endorsed by most rheumatologists except in the mildest cases of AS. | ||||||||||||
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Abstract 364 Analysis Of Acute Spinal Changes In Ankylosing Spondylitis: The Systemic Comparison Of Conventional X-Rays With Magnetic Resonance Imaging (MRI Using Established And New Scoring Systems) This study evaluates the use of conventional radiographs as well as magnetic resonance imaging (MRI) in detecting acute changes in the spine of patients with ankylosing spondylitis. MRI results were compared to plain x-rays in thirty-nine patients with ankylosing spondylitis. These were graded with established grading systems by independent readers. Results: This study showed that MRI techniques can be used to evaluate active lesions in ankylosing spondylitis. Such lesions include bone marrow edema. The area most intensively involved in these patients based on MRI was the thoracic spine. They did compare two MRI techniques, one using gadolinium and the other using a STIR-weighted sequences. These two imaging modalities were comparable. This inflammation cannot be seen on standard radiographs. Editorial Comment: These studies provide further evidence that MRI may be an effective method for determining acute inflammation in patients with ankylosing spondylitis. This will become a critical tool in further studies looking at interventions in ankylosing spondylitis. | ||||||||||||
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Abstract 350 Assessments Of Disease Activity And Functionality In Enbrel-Treated Patients With Ankylosing Spondylitis In A Multi-Center, Placebo-Controlled Trial This study evaluated the response to Enbrel in patients with ankylosing spondylitis. Eighty-four patients were enrolled in this placebo-controlled double-blind study to receive either the active agent (Enbrel 25 mg biweekly) or placebo. This study was carried out for twelve weeks. Outcomes measured included markers for inflammation, fatigue, and the ability to do specific functional tasks. Results: Etanercept-treated patients showed improvement in these outcomes. There was also a marked reduction in fatigue in the treated patients. In this short study, the only adverse event reported more frequently in the Enbrel group was injection site reactions. Editorial Comments: This is yet another study that shows the efficacy of TNF inhibitor therapy in patients with ankylosing spondylitis. It demonstrates the rapid improvement in not only functional symptoms, but also in the constitutional symptom of fatigue. | ||||||||||||
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Abstract 365 Effects Of Etanercept (Enbrel®) On Spinal And Hip Bone Mineral Density In Patients With Ankylosing Spondylitis: Twenty-Four Week Data This study evaluates the effect of Etanercept therapy on the bone mineral density within the spine and hip of patients with ankylosing spondylitis. Bone mineral density was analyzed in twenty-two patients treated with Etanercept versus eighteen patients treated with placebo before and after treatment. Results: In those patients receiving Etanercept treatment, there was evidence of increase in bone mineral density in the spine of 3% but not in the hip over a 24-week period.
Editorial Comments: It is felt that the chronic inflammation, as well as immobility that occurs with ankylosing spondylitis, may lead to bone mineral loss. This study suggests that Etanercept has an effect in preventing this loss in the spine. | ||||||||||||
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Abstract 353 Socioeconomic Consequences For Patients With Active Ankylosing Spondylitis Treated For Two Years With Infliximab In A Clinical Trial This study evaluated the socioeconomic consequences of patients with ankylosing spondylitis to determine if therapy can improve this outcome in patients with ankylosing spondylitis. The same group of seventy patients previously described was followed to evaluate their work status throughout the course of the study. Specifically, they looked at days of sick leave and days of hospitalization in the year prior to therapy and compared these outcomes in the year after initiating therapy. Results: The average age of these patients was nearly forty years old, with two-thirds of the patients being of male gender. In those patients who were able to continue with the study drug, there was reduction in the amount of sick leave, as well as a reduction in the need for hospitalization by 50% after one year of therapy. Editorial Comment: This information does provide further support for the benefit of this therapy. This shows not only decrease in direct healthcare costs from hospitalization, but also decrease in the indirect costs that occur due to absence from work. Further evaluation will need to be required for formal cost effectiveness analysis. | ||||||||||||
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Abstract 352 Two-Year Follow-Up Results Of Controlled Trial Of The Anti-TNF Alpha Antibody Infliximab In Active Ankylosing Spondylitis This trial is a follow-up of seventy patients who were initially randomized to placebo versus Infliximab therapy. After one year, those patients randomized to placebo were then switched to receive anti-TNF therapy and the trial was continued for a second year. Patients received Infliximab at 5 mg/kg every six weeks through the duration of the study. Of the original seventy patients entered into the study, twenty-one dropped out primarily due to adverse events, or due to lack of response. Those patients treated for a total of two years showed significant reduction in their disability with nearly half the patients showing a 50% reduction in their disability indices. In those patients that were able to maintain Infliximab therapy, the improvement was persistent. Editorial Comment: Up to 30% of patients did not complete the two-year study. Twenty-percent did develop adverse events leading to drop out. This included one case of tuberculosis, one case of herpes zoster (shingles), and another case of cutaneous lupus. There was also a patient who developed polyarthritis with a positive ANA, but no anti-DNA antibodies. Thus, while this therapy can offer sustained reduction in symptoms of ankylosing spondylitis, the therapy needs to be monitored carefully. | ||||||||||||
| Psoriatic Arthritis and Psoriasis | ||||||||||||
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Abstract 342 Leflunomide In The Treatment Of Psoriatic Arthritis And Psoriasis: Joint And Skin Efficacy And Safety In The TOPAS Study This study looks at the use of Leflunomide in patients with psoriatic arthritis to determine the response of both their skin and their arthritis to this therapy. One-hundred-and-ninety patients with active psoriatic arthritis and psoriasis were randomized to either placebo or Leflunomide for a twenty-four week period. Patients were then assessed for improvement in their joints and pain based on the modified American College of Rheumatology 20% (ACR-20) response rate, as well as improvement in the degree of their cutaneous psoriasis. They use a psoriatic arthritis response criteria to determine response (PsARC). Results: In this study, nearly 60% of patients did develop a response by PsARC criteria at the end of twenty-four weeks. This was compared to 30% of patients given placebo. As measured by the modified ACR-20 criteria, 36% of treated patients versus 20% of those with placebo demonstrated improvement. Also, there was improvement in cutaneous scores used to assess the degree of psoriasis. Side effects were more common in the treated group with 24% of patients developing diarrhea (compared to 13% of placebo) and 12.5% showing mild liver function abnormalities (compared to 5.5% in placebo group). Editorial Comment: Leflunomide is used in patients with rheumatoid arthritis. This study shows that it is superior to placebo in treating both the cutaneous and articular symptoms of patients with psoriatic arthritis. The safety profile within this short study is comparable to that seen in patients with rheumatoid arthritis. It does require frequent monitoring. The efficacy compared to TNF therapy was not measured in this study. Leflunomide is yet another treatment possibility for psoriatic arthritis. There are no radiographic outcomes presented with this study. This will be important information to gather in the future to determine the effectiveness of this intervention. | ||||||||||||
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Abstract 337 Infliximab Improves Signs Of Plaque Psoriasis In Patients With Psoriatic Arthritis This abstract describes the efficacy of Infliximab therapy on plaque psoriasis in patients with psoriatic arthritis. Seventy-eight patients were randomized to three treatment arms (placebo, 3 mg/kg, or 5 mg/kg of Infliximab at weeks zero, two, and six). Results: Ten weeks after initiating therapy, there was a significant improvement of psoriasis in patients treated with Infliximab compared to those treated with placebo. This improvement typically occurred after four weeks of initiating therapy; concomitant with this was an improved health-related quality of life in these patients. No serious reactions were noted during this short-term study. Editorial Comment: These data confirm the efficacy of TNF therapy for cutaneous manifestations of psoriasis. As this is a short-term study, long-term evaluation will need to be performed. | ||||||||||||
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