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This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - 74th Annual Meeting of the American College of Rheumatology and the 45th Annual Meeting of the Association of Rheumatology Health Professionals

Atlanta, Georgia / November 7-11, 2010

The Psoriatic Arthritis Screening and Evaluation (PASE) is a validated tool originally designed to screen for active psoriatic arthritis (PsA) among individuals with psoriasis and is now being evaluated as a measurement of treatment response (Husni et al. J Am Acad Dermatol 2007;57:581-7, Dominguez et al. Arch Dermatol Res 2009;301:573-9). Dr. M. Elaine Husni, Vice Chair of Rheumatology and Director, Arthritis and Musculoskeletal Center, Cleveland Clinic, Ohio, presented the first results validating the PASE questionnaire as a useful tool for PsA screening and evaluation of treatment effect within a controlled clinical trial setting.

PASE: Evaluating Treatment Response

The PASE questionnaire consists of 15 questions divided into 2 subscales, with 7 questions assessing symptoms and 8 questions assessing function. The scoring system has a cutoff total score of 47, with active PsA present if the score is =47 and absent if <47. Dr. Husni and colleagues administered the questionnaire to patients participating in PRISTINE (Psoriasis Study to Assess Efficacy and Safety in Subjects Taking Etanercept 50 mg Once Weekly and Twice Weekly with Adjunct Therapy) at baseline and after 12 weeks of treatment. PRISTINE randomized 273 adult patients with moderate to severe psoriasis to either etanercept 50 mg once or twice weekly over 12 weeks (double-blind phase), followed by 50 mg once weekly in all patients for a further 12 weeks (open-label phase) (Strohal et al. J Invest Dermatol 2010;130:70, Abs 404).

At baseline, 31% of patients had a self-reported history of PsA and 25% had a PASE total score =47, indicating the presence of PsA. After 12 weeks of treatment, the percentage of patients with PASE total score =47 decreased in both treatment groups, with no significant differences between them. Significant improvement was seen in median PASE scores for symptoms and function in both groups (P<0.01 within each group). Median per cent changes in total score were -6.6% and -10.0% in the twice-weekly and once-weekly groups, respectively. These results confirmed the findings from PRESTA (Psoriasis Randomized Etanercept Study in Subjects with Psoriatic Arthritis) that both schedules produced comparable joint improvement but further analysis is needed. Dr. Husni confirmed, “Further studies are needed to determine whether changes in biomarkers such as CRP, sleep or fatigue correlate with changes in PASE scores as patients respond to treatment for PsA.”

Newly Proposed Disease Activity Scores

To assess function in patients with PsA, 2 composite disease activity measures have recently been proposed: the Composite Psoriatic Disease Activity Index (CPDAI) (Mumtaz et al. Ann Rheum Dis epub November 29, 2010) and the Disease Activity Index for Psoriatic Arthritis (DAPSA) (Nell-Duxneuner et al. Ann Rheum Dis 2010;69:546-9). A study that compared the performance of these 2 measures using data from PRESTA has shown that both are effective in determining treatment response in these patients, but that only CPDAI determines a wider range of response. The results of this study were presented by Prof. Oliver M. FitzGerald, St. Vincent’s University Hospital and the Conway Institute, University College Dublin, Ireland. “The PRESTA data provided an excellent opportunity to evaluate the 2 composite measures in PsA,” noted Prof. FitzGerald.

PRESTA was the first randomized, double-blind study to evaluate the safety and efficacy of 2 doses of etanercept on skin and joint disease in psoriasis subjects with active PsA, defined as =2 swollen joints and =2 tender/painful joints, subject-reported joint pain for =3 months and negative serum rheumatoid factor within 6 months. Eligibility criteria also included clinically stable plaque psoriasis (=10% of body surface area) and a subject global assessment of “moderate” or “worse” at screening. A total of 752 patients were randomized to receive subcutaneous (s.c.) etanercept 50 mg twice-weekly or once-weekly for 12 weeks, followed by open-label etanercept 50 mg once-weekly for 12 additional weeks.

All patients showed significantly improved PsA symptoms with treatment, regardless of treatment group (Sterry et al. BMJ 2010;340:c147). The twice-weekly etanercept group showed significantly greater improvement in the Psoriasis Area and Severity Index (PASI), but both groups were equally likely to meet American College of Rheumatology (ACR) criteria for treatment response.

Using baseline, 12- and 24-week data from the study, Prof. FitzGerald and colleagues calculated CPDAI scores using 4 domains: joints (66 swollen joint count [SJC]/68 tender joint count [TJC]); Health Assessment Questionnaire (HAQ); skin (PASI) and Dermatology Life Quality Index (DLQI); dactylitis (each digit rated 0-3); and enthesitis (number of tendons showing enthesitis, 0-4, based on Achilles tendons and plantar fasciae bilaterally). DAPSA scores were calculated as the sum of 5 components: subject global assessment (0-10 visual analogue scale [VAS]); subject assessment of pain (0-10 VAS); SJC; TJC; and C-reactive protein (CRP).

Both CPDAI and DAPSA could distinguish response to treatment comparing baseline and 12- or 24-week values (P<0.0001 for all). However, only CPDAI could distinguish global treatment response between the 2 etanercept doses at 12 weeks (P=0.0492), Prof. FitzGerald reported. Neither index could distinguish response at 24 weeks. All domains contributed to the data variability of the CPDAI, most significantly with dactylitis and enthesitis. Joint scores contributed the most to DAPSA variability. The components most significantly associated with change in CPDAI from baseline were change in enthesitis, DAS 28, HAQ, dactylitis and DLQI. For DAPSA, changes in all 5 components were significantly associated.

Investigators concluded that CPDAI is the only composite score of the 2 tested that not only determines response in terms of joint disease, but also other domains deemed important for adequate assessment in subjects with PsA such as skin, enthesitis and dactylitis. In contrast, DAPSA’s primary focus is assessment of joint disease activity.

Uveitis in Juvenile Idiopathic Arthritis

Uveitis occurs in 10% of patients with polyarticular juvenile idiopathic arthritis (JIA). Topical corticosteroids remain first-line treatment, followed by the addition of DMARDs such as methotrexate or cyclosporine, progressing to anti-TNF therapy for resistant disease. New data from the German Etanercept Registry indicate that a combination of etanercept and methotrexate (MTX) is most effective in preventing uveitis flares in patients with JIA, according to a study presented by Dr. Ivan Foeldvari, Hamburger Zentrum für Kinder- und Jugendrheumatologie, Germany. He noted that trials of etanercept vs. placebo produced conflicting results and in a retrospective study there was no significant change in number of uveitis flares before or after therapy (Schmeling H, Horneff G. Rheumatology (Oxford) 2005;44:1008-11).

The German Etanercept Registry was launched in 2001 to track etanercept usage in children with JIA treated at pediatric centres in Germany and Austria (Horneff et al. Ann Rheum Dis 2004;63:1638-44). Dr. Foeldvari and colleagues reviewed the prevalence of uveitis or new-onset uveitis and evaluated different treatments in 868 patients. These patients received 1 of 8 treatments: etanercept monotherapy; etanercept + steroids; etanercept + MTX; etanercept + MTX + steroids; etanercept + other DMARDs; etanercept + other DMARDs + steroids; or etanercept + MTX + other DMARDs + steroids. The other DMARDs were usually leflunomide or sulfasalazine. The largest groups were etanercept + MTX (246 patients) and etanercept + steroids (290 patients).

Over the course of treatment, the lowest rate of uveitis (2%) was seen in patients taking etanercept/MTX and in patients taking etanercept/MTX/steroids. This translated into a rate of new-onset uveitis of 0.9/100 patient-years in the combination therapy groups compared with 3.5/100 patient-years in the etanercept monotherapy group. “Interestingly, the other DMARDs did not have the same protective effect as etanercept on uveitis,” Dr. Foeldvari pointed out. He added that the time to onset of new uveitis was also significantly longer in the children on combination therapy than in the etanercept monotherapy group. “These data suggest that MTX and etanercept can prevent some cases of new-onset uveitis. Patients with a history of uveitis should receive combination therapy of etanercept and MTX to prevent uveitis flares,” he concluded.

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