Alefacept treatment in psoriatic arthritis: Reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis

Kraan, Maarten C.; Kuijk, Arno W R van; Dinant, Huibert J.; Goedkoop, Amber Y.; Smeets, Tom; Rie, Menno A. de; Dijkmans, Ben A. C.; Vaishnaw, Akshay; Bos, Jan D.; Tak, Paul P.

doi:10.1002/art.10543

Cited by 135 publications

(74 citation statements)

References 60 publications

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“…74 Most research with synovial biopsies has been performed from RA patients but some results suggest that synovial tissue sampling may be used in other inflammatory arthropathies such as psoriatic arthritis. 71,[75][76][77] This research aims to gain a fuller understanding of disease pathogenesis, mechanisms of action of current treatments, and the identification of novel targets and biomarkers. Indeed, the effects of various treatments for RA on the synovium has been studied, and the principal results of these data are presented in table 1.…”

Section: Retrieving Synovial Tissue Samplesmentioning

confidence: 99%

Synovial tissue research: a state-of-the-art review

et al. 2017

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The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis (RA). The study of synovial tissue has advanced significantly over a number of decades from arthroplasty, blind needle biopsy and more recently facilitated by arthroscopic and ultrasonographic technology that allows easier visualisation and improves the reliability of obtaining synovial biopsies. The potential for study of pathogenesis, patient stratification, discovery of biomarkers and novel targets, as well as validation of therapy, have all been progressed rapidly in the last decade, facilitated by increasingly diverse and sophisticated analytical and technological approaches. In this review we describe clinical and translational developments in the field of synovial tissue research, outlining current and novel investigative technologies, and highlight their application to advance our understanding of the aforegoing imperatives.3

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Section: Retrieving Synovial Tissue Samplesmentioning

confidence: 99%

Synovial tissue research: a state-of-the-art review

et al. 2017

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“…In addition, discontinuation rates due to lack of response and adverse events are typically high for conventional systemic therapies (38), and longterm safety is a concern (39,40). Two biologic agents, etanercept and infliximab, have recently been shown to be effective in the treatment of PsA, and these agents along with alefacept also reduce psoriasis symptoms (17)(18)(19). These therapies require injections or infusions, and cost may be a barrier to their use.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a tumor necrosis factor (TNF) inhibitor, etanercept, has demonstrated significant efficacy in the treatment of PsA and psoriasis (17), and preliminary data suggest the same for the TNF inhibitor infliximab (18). Another biologic agent, alefacept, a lymphocyte function-associated antigen 3 fusion protein that blocks T cell activation, is available for the treatment of psoriasis and may also be useful in PsA (19). These biologic agents must be administered by injection or infusion and are costly.…”

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Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: A multinational, double‐blind, randomized, placebo‐controlled clinical trial

Kaltwasser

Nash

Gladman

et al. 2004

Arthritis & Rheumatism

377

194

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Objective. Current treatment options for psoriatic arthritis (PsA) are limited. Leflunomide, an oral pyrimidine synthesis inhibitor, is highly effective in the treatment of rheumatoid arthritis, and small studies have suggested similar efficacy in PsA. We undertook this double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of leflunomide in patients with PsA and psoriasis.Methods. One hundred ninety patients with active PsA and psoriasis (at least 3% skin involvement) were randomized to receive leflunomide (100 mg/day loading dose for 3 days followed by 20 mg/day orally) or placebo for 24 weeks. The primary efficacy end point was the proportion of patients classified as responders by the Psoriatic Arthritis Response Criteria (PsARC). Additional efficacy (joint and skin involvement), safety, and quality-of-life assessments were performed.Results Conclusion. Leflunomide is an effective treatment for PsA and psoriasis, providing a safe and convenient alternative to current therapies.

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“…Activated T cells bearing markers of antigen activation are abundant in the inflamed joint and skin (18). Alefacept, a fusion protein that inhibits T cell activation by blocking the interaction of lymphocyte function-associated antigen with CD2, has been shown to improve the psoriatic skin lesions and the signs and symptoms of arthritis in patients with active PsA (19)(20)(21). The beneficial effect of TNF blockade in PsA is associated with a marked decrease in synovial T cell infiltration (22).…”

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confidence: 99%

Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II trial

Mease¹,

Genovese²,

Gladstein³

et al. 2011

Arthritis & Rheumatism

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Objective. To assess the safety and efficacy of abatacept, a selective T cell costimulation modulator, in patients with psoriatic arthritis (PsA).Methods. In this 6-month, multicenter, randomized, double-blind, placebo-controlled, phase II study, 170 PsA patients with a psoriasis target lesion (TL) >2 cm who had previously taken disease-modifying antirheumatic drugs (DMARDs), including anti-tumor necrosis factor (anti-TNF) agents, were randomized (1:1: 1:1) to receive placebo or abatacept at doses of 3 mg/kg, 10 mg/kg, or 30/10 mg/kg (2 initial doses of 30 mg/kg, followed by 10 mg/kg) on days 1, 15, and 29 and then once every 28 days thereafter. The primary end point was the American College of Rheumatology 20% criteria for improvement (ACR20 response) on day 169. Other key end points were magnetic resonance imaging (MRI) scores for joint erosion, osteitis, and synovitis, scores on the Health Assessment Questionnaire (HAQ) and the Short Form-36 (SF-36) health survey, the investigator's global assessment of psoriasis, the TL score, and the Psoriasis Area and Severity Index (PASI) score.Results. Proportions of patients achieving an ACR20 response were 19%, 33%, 48%, and 42% in the placebo, the abatacept 3 mg/kg, the abatacept 10 mg/kg, and the abatacept 30/10 mg/kg groups, respectively. Compared with placebo, improvements were significantly higher for the abatacept 10 mg/kg (P ‫؍‬ 0.006) and 30/10 mg/kg (P ‫؍‬ 0.022) groups, but not for 3 mg/kg group (P ‫؍‬ 0.121). All abatacept regimens resulted in improved MRI, HAQ, and SF-36 scores, with 10 mg/kg showing the greatest improvements. Improvements in the TL and PASI scores were observed in all abatacept arms; a response according to the investigator's global assessment was seen only with 3 mg/kg of abatacept. The safety profiles were similar among the treatment arms.Conclusion. The results of this study suggest that 10 mg/kg of abatacept, the approved dosage for rheumatoid arthritis and juvenile idiopathic arthritis, may be an effective treatment option for PsA.Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by both arthritis and psoriasis ClinicalTrials.gov identifier: NCT00534313.

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Alefacept treatment in psoriatic arthritis: Reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis

Cited by 135 publications

References 60 publications

Synovial tissue research: a state-of-the-art review

Synovial tissue research: a state-of-the-art review

Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: A multinational, double‐blind, randomized, placebo‐controlled clinical trial

Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II trial

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