Literature on Psoriatic Arthritis

Efalizumab for the treatment of psoriatic arthritis.

J Cutan Med Surg. 2007 Mar-Apr;11(2):57-66

Authors: Papp KA, Caro I, Leung HM, Garovoy M, Mease PJ

BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. Efalizumab, a T cell-targeted, recombinant human monoclonal antibody, is approved for the treatment of adult patients with chronic moderate to severe plaque psoriasis. The effect of efalizumab therapy on PsA has not previously been investigated. OBJECTIVE: This phase II randomized, double-blind, placebo-controlled multicenter study evaluated the efficacy and safety of efalizumab for the treatment of PsA. METHODS: Patients were required to be on at least one of the following concomitant systemic therapies for PsA: nonsteroidal anti-inflammatory drugs, corticosteroids, and/or sulfasalazine or methotrexate. One hundred fifteen patients with active PsA were enrolled and randomized in the study. Of these, 107 were treated weekly with efalizumab 1 mg/kg or placebo for 12 weeks, followed by 12 additional weeks of open-label efalizumab. RESULTS: At week 12, 28% of efalizumab-treated patients achieved ACR-20 response (a 20% reduction from the baseline in the American College of Rheumatology response criteria), the primary end point, compared with 19% of placebo patients (p = .27). The safety profile was comparable between efalizumab- and placebo-treated patient groups, regardless of methotrexate background therapy, and no worsening of joint disease occurred with efalizumab therapy. CONCLUSIONS: Efalizumab was not effective in treating PsA; efalizumab therapy did not worsen PsA. The efalizumab safety profile does not appear to be altered with the concomitant use of methotrexate therapy.

PMID: 17374316 [PubMed - in process]

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Concepts important to patients with psoriatic arthritis are not adequately covered by standard measures of functioning.

Arthritis Rheum. 2007 Mar 29;57(3):487-494

Authors: Stamm TA, Nell V, Mathis M, Coenen M, Aletaha D, Cieza A, Stucki G, Taylor W, Smolen JS, Machold KP

OBJECTIVE: To explore whether the concepts important to patients with psoriatic arthritis (PsA) are covered by self-report instruments assessing functioning. METHODS: We conducted a qualitative focus group study with PsA patients about their problems in daily functioning. Focus groups were tape recorded and transcribed verbatim. The transcribed texts were divided into meaning units, and concepts contained in these meaning units were extracted. Self-report instruments assessing functioning in PsA were identified in a structured literature search. Using the International Classification of Functioning, Disability and Health (ICF) as a common frame of reference, we determined whether each concept identified in the focus groups was covered by each of the instruments. RESULTS: Thirty-one patients participated in 6 focus groups. The following 9 instruments were included in the present analysis: Arthritis Impact Measurement Scale Short Form; Bath Ankylosing Spondylitis Disease Activity Index; Disabilities of the Arm, Shoulder, and Hand Questionnaire; Dermatology Quality of Life Index; Dougados Functional Index; Health Assessment Questionnaire (HAQ); HAQ-S (HAQ adapted for spondylarthropathies); PsA-specific Quality of Life Instrument; and Short Form 36 Health Survey. Of the 54 concepts identified in 590 meaning units in the transcribed data, 19 concepts (35%) were not covered by any of the instruments. Of these, 11 concepts that were linked to the ICF component environmental factors were not covered by any of the instruments, whereas all concepts linked to the ICF component activities and participation were covered by at least 1 of the instruments (but no single instrument covered all concepts). CONCLUSION: The impact of environmental factors, attitudes towards individuals with health problems, and loss of leisure time may represent important aspects addressing participation that are currently not covered in the instruments assessing functioning in PsA.

PMID: 17394177 [PubMed - as supplied by publisher]

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What is juvenile psoriatic arthritis? Comment on the article by Stoll et al.

Arthritis Rheum. 2007 Mar 28;56(4):1368

Authors: Martini A

PMID: 17393443 [PubMed - as supplied by publisher]

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Psoriatic arthritis: Current concepts on pathogenesis-oriented therapeutic options.

Arthritis Rheum. 2007 Mar 28;56(4):1051-1066

Authors: Turkiewicz AM, Moreland LW

PMID: 17393414 [PubMed - as supplied by publisher]

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Cytokine gene polymorphisms in Chinese patients with psoriasis.

Br J Dermatol. 2007 Mar 28;

Authors: Chang YT, Chou CT, Yu CW, Lin MW, Shiao YM, Chen CC, Huang CH, Lee DD, Liu HN, Wang WJ, Tsai SF

Background Previous studies have shown that cytokine gene polymorphisms may confer susceptibility to psoriasis. Objectives To determine whether genetic polymorphisms of the cytokine genes might influence the development of psoriasis in Chinese patients in Taiwan. Methods DNA samples were obtained from 170 patients with psoriasis vulgaris (PV), 102 patients with psoriatic arthritis (PsA) and 210 control subjects. Using direct sequencing and microsatellite genotyping, we examined 28 polymorphisms in 11 cytokine genes including the interleukin (IL)-1alpha, IL-1beta, IL-1 receptor antagonist, IL-4, IL-8, IL-10, IL-12B, IL-13, tumour necrosis factor (TNF)-alpha, TNF-beta and interferon-gamma genes. Genotypes of HLA-Cw*0602, killer cell immunoglobulin-like receptor (KIR) genes and major histocompatibility complex class I chain-related gene A (MICA) were also determined in patients with PsA. Results The patients with PV were more likely to carry the +4496G allele of the IL-12B gene (59.4% vs. 49.3%, P = 0.0067, P(c) = 0.033). However, no significantly different allelic and genotypic distributions of the other analysed genes including IL-1beta, TNF-alpha, TNF-beta, KIR genes and MICA were found between the PV/PsA patients and controls. Moreover, no association was observed with disease onset, gender, peripheral arthritis or joint erosion. With regards to HLA-Cw*0602, its allele frequency was significantly increased in patients with early-onset PV (25.3% vs. 4.8%, P

PMID: 17388919 [PubMed - as supplied by publisher]

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Expression of extra trinucleotide in CD44 variant of rheumatoid arthritis patients allows generation of disease-specific monoclonal antibody.

J Autoimmun. 2007 Mar 22;

Authors: Golan I, Nedvetzki S, Golan I, Eshkar-Sebban L, Levartovsky D, Elkayam O, Caspi D, Aamar S, Amital H, Rubinow A, Naor D

Selective targeting of cells engaged in pathological activities is a major challenge for medical research. We generated monoclonal antibodies (mAbs) that exclusively bind, at concentrations ranging from 2 to 100mug/ml, to a modified CD44 variant (designated CD44vRA) expressed on synovial fluid cells from joints of rheumatoid arthritis (RA) patients. These mAbs cross-reacted with keratinocytes expressing wild type CD44vRA (CD44v3-v10) only at a relatively high concentration (200mug/ml). Sequence analysis of CD44vRA cDNA revealed, in 33 out of 43 RA and psoriatic arthritis patients, an extra intron-derived trinucleotide, CAG, which allows translation of an extra alanine. This insertion imposes a configurational change on the cell surface CD44 of RA synovial fluid cells, creating an immunogenic epitope and potentiating the ability to produce disease-specific antibodies. Indeed, the anti-CD44vRA mAbs (designated F8:33) were able to induce apoptosis in synovial fluid cells from RA patients, but not in peripheral blood leukocytes from the same patients, in keratinocytes from normal donors or in synovial fluid cells from osteoarthritis patients. Furthermore, injection of anti-CD44vRA mAbs reduced joint inflammation in DBA/1 mice with collagen-induced arthritis. These findings show that anti-CD44vRA mAbs are both bioactive and RA-specific.

PMID: 17383158 [PubMed - as supplied by publisher]

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Reductions in healthcare resource utilization in psoriatic arthritis patients receiving etanercept therapy: results from the educate trial.

J Drugs Dermatol. 2007 Mar;6(3):299-306

Authors: Kimball AB, Jackson JM, Sobell JM, Boh EE, Grekin S, Pharmd EB, Woolley JM, Xia HA, Chiou CF, Stevens SR

The Experience Diagnosing, Understanding Care, and Treatment with Enbrel (EDUCATE) trial is a phase IV, 24-week, multicenter, open-label study of etanercept 50 mg weekly in the treatment of psoriatic arthritis (PsA) in community dermatology clinics. In this study, patients with active PsA and moderate to severe plaque psoriasis have measurable uses of healthcare resources at baseline, reflecting a burden of illness. Etanercept significantly reduced healthcare resource utilization, absenteeism, and caregiver assistance in PsA patients after 24 weeks of treatment. These results could translate into savings on both direct and indirect costs and improvements in health-related quality of life for patients with PsA.

PMID: 17373192 [PubMed - in process]

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Lymphocytes and synovial fluid fibroblasts support osteoclastogenesis through RANKL, TNFalpha, and IL-7 in an in vitro model derived from human psoriatic arthritis.

J Pathol. 2007 Mar 16;

Authors: Colucci S, Brunetti G, Cantatore F, Oranger A, Mori G, Quarta L, Cirulli N, Mancini L, Corrado A, Grassi F, Grano M

Psoriatic arthritis (PsA) is an inflammatory joint disease, characterized by extensive bone resorption, whose mechanisms have not been fully elucidated. Thus, in the present study we investigated the involvement of RANKL, TNFalpha, and IL-7 in the osteoclastogenesis of PsA patients. In vitro osteoclastogenesis models, consisting of unfractionated and T-cell-depleted mononuclear cells from peripheral blood (PBMCs) and synovial fluid (SFMCs) of 20 PsA patients as well as from healthy donors were studied. Freshly isolated T and B cells from PBMCs and T cells and fibroblasts from SFMCs of PsA patients were subjected to RT-PCR to detect the levels of RANKL, TNFalpha, and IL-7. Osteoclastogenesis was studied in the presence of RANK-Fc, anti-TNFalpha, and anti IL-7 functional antibodies. We demonstrate that lymphocytes and fibroblasts support osteoclast (OC) formation in PsA patients through the production of osteoclastogenic cytokines. In particular, OC formation was completely abolished in unstimulated T cell-depleted PBMC cultures, and reduced by approximately 70% in unstimulated T cell-depleted SFMC cultures. Freshly isolated T cells from PBMCs and SFMCs of PsA patients overexpressed RANKL and TNFalpha, while fibroblasts from synovial fluid produced only RANKL. We show that the presence of RANK-Fc and/or anti-TNFalpha functional antibodies reduced OC formation. Moreover, T and B cells from PBMCs as well as T cells and fibroblasts from SFMCs expressed IL-7 mRNA. Finally, the anti-IL-7 functional antibody significantly reduced osteoclastogenesis. Our results suggest that fibroblasts, B and T lymphocytes support OC formation by producing RANKL, TNFalpha, and IL-7, contributing to the aggressive bone resorption in PsA patients. Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PMID: 17370327 [PubMed - as supplied by publisher]

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Tuberculous uveitis after treatment with etanercept.

Graefes Arch Clin Exp Ophthalmol. 2007 Mar 16;

Authors: Fonollosa A, Segura A, Giralt J, Garcia-Arumi J

BACKGROUND: Etanercept is a tumor necrosis factor (TNF) inhibitor that has been licensed in the United States for the treatment of adult and juvenile rheumatoid arthritis as well as psoriatic arthritis. Reactivation of tuberculosis is a complication of its use. We report the first case of tuberculous uveitis due to etanercept. METHODS: We performed a clinical chart review. CASE: A 58-year-old Caucasian woman was referred to our hospital for chronic unilateral granulomatous panuveitis of the right eye (RE). She was on etanercept and methotrexate for rheumatoid arthritis. Since the patient was immunosuppressed with etanercept and since the uveitis was granulomatous we considered tuberculosis as a possible etiology. An aqueous humor tap was performed and sent for polymerase chain reaction analyses of Herpes simplex, Herpes zoster, and Mycobacterium tuberculosis (MT). This last test was positive. Another aqueous humor sample was taken and sent for microscopic examination of sputum for acid-fast bacilli and culture, both of which were positive for MT. A diagnosis of tuberculous uveitis was established; the patient was treated with rifampin, isoniazid pyrazinamide, and ethambutol and etanercept was stopped. Four months later there were no cells in the anterior chamber and the vitreous was clear. DISCUSSION: To our knowledge this is the first reported case of tuberculous uveitis following treatment with etanercept. This etiology has to be considered in patients taking this drug who present with intraocular inflammation.

PMID: 17364199 [PubMed - as supplied by publisher]

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Complications and adverse reactions in the use of newer biologic agents.

Semin Cutan Med Surg. 2007 Mar;26(1):6-14

Authors: Callen JP

New developments in genetic engineering and biotechnology have allowed the creation of bioengineered molecules that target specific steps in the pathogenesis of several immune-mediated disorders, including Crohn’s disease, rheumatoid arthritis, psoriasis and psoriatic arthritis, ankylosing spondylitis, pemphigus, and B-cell lymphoma. These drugs work by eliminating pathogenic T cells (alefacept), blocking T-cell activation and/or inhibiting the trafficking of T cells (efalizumab), changing the immune profile from Th1 to Th2, blocking cytokines (eg, tumor necrosis factor alpha antagonists including etanercept, infliximab and adalimumab, or interleukin-1-receptor antagonists [anakinra]), or eliminating pathogenic B cells (rituximab). This article reviews the complications and adverse reactions associated with these medications.

PMID: 17349557 [PubMed - in process]

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