Guselkumab: the First Selective IL-23 Inhibitor for Active Psoriatic Arthritis in Adults.

INTRODUCTION: Guselkumab is a subcutaneously administered human monoclonal antibody, selectively blocking IL-23 through binding to its p19 subunit. It was initially approved for the treatment of patients with moderate-to-severe plaque-psoriasis who are candidates for systemic therapy or phototherapy. Pubmed and Embase databases were searched for publications, using the following search terms: psoriasis, psoriatic arthritis, guselkumab, risankizumab, tildrakizumab, p19, interleukin 23, guidelines, treatment recommendations, DISCOVER, ECLIPSE, and VOYAGE. AREAS COVERED: Accumulating evidence suggests that the IL-23/Th17 pathway is important in the pathogenesis of both psoriasis and psoriatic arthritis. Following a successful development program in psoriasis, guselkumab was evaluated for its efficacy and safety in psoriatic arthritis in a comprehensive clinical trial program, comprising one phase-2 study and two phase-3 studies (DISCOVER-1 and -2). Complementary data on pharmacokinetics and safety exist from pre-clinical experiments and pooled analyses from two long-term studies in psoriasis (VOYAGE-1 and -2). Based on the DISCOVER-1 and -2 data, guselkumab was approved by the FDA for the treatment of active psoriatic arthritis in 2020. EXPERT OPINION: Guselkumab is the first selective IL-23 inhibitor approved to treat adults with active psoriatic arthritis, broadening therapeutic options in the field through a novel mode of action.

Pathogenesis of Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy involving synovial and entheseal structures, associated with psoriasis or similar conditions. The etiopathogenetic mechanisms underlying PsA remain unclarified. The most accredited hypothesis involves a complex interaction among genetic, environmental, and immunological factors. Environmental agents, particularly trauma, mechanical stress, and smoke have been cited as possible factors in triggering the disease in genetically predisposed subjects. Like other forms of spondyloarthropathies, PsA shows several genetic associations with the major histocompatibility complex (MHC) class I alleles located on chromosome 6p21.3, particularly the human leukocyte antigen (HLA)-B27 in axial phenotypes. Recent studies have demonstrated that the most common epigenetic mechanisms that regulate gene expression in PsA are represented by DNA methylation, parent of origin effect or genomic imprinting, expression or activity of epigenetic modifying enzymes, and RNA interference (RNAi) by microRNAs (miRNAs). The mechanisms underlying PsA pathogenesis activate the innate and adaptive immune system and overexpression of TNF associated with amplification of the IL-23/IL-17 axis. In recent years, more PsA susceptibility genes and epigenetic mechanisms have been identified. Advances in the knowledge of innate and adaptive immune mechanisms underlying PsA have contributed to a better understanding of the heterogeneous clinical expression of the disease and, thus, to therapy strategies. The complexity of the pathogenetic aspects involving multiple cytokines, cell lines, and molecules needs to be further investigated to advance personalized therapeutic strategies and to improve outcomes of patients affected by PsA.

Modern specific features and therapy of psoriasis and arthropathic psoriasis courses.

OBJECTIVE: Introduction:Psoriasis affects about 2% of population. In 30-40% of occurrences arthropathic psoriasis (AP) is diagnosed and it leads to 11-19% of disability cases development. Recent studies have shown that psoriasis is often synergistically combined with herpesvirus of the 1st and 2nd type, which, according to many scientists, determines the severity, frequency of recurrences, and the course of this dermatosis. Recently, new biomarkers, i.e. a system of small ribonucleic microRNA acids, have been described. Their role and interconnection in respect of regulation of congenital and acquired immunity activity in patients with herpesvirus infection at psoriasis has been defined. The article analyses features of anamnesis, clinical, instrumental and laboratory tests related to arthropathic psoriasis, considers the relationship of probable mechanisms of disease aggravation and progression with the definition of a treatment method influencing the dynamics of a disease course. The aim of our work was to improve the diagnostics of AP patients taking into account some indicators of the immune-endocrine system and features of the disease course to specify their role in AP pathogenesis and to develop the system of integrated therapy of patients whose locomotor system is affected due to psoriasis. PATIENTS AND METHODS: Materials and methods: A total of 178 AP patients have been systematically examined. We have examined AP patients with varying severity of process development, generalization and the severity of skin and osseous-articular apparatus damage, the presence of associated pathology. Additional instrumental studies, determination of biochemical, serological parameters and an assessment of stress-induced immune-endocrine system have been conducted in AP patients. The content of trigger cytokines (IL-1ß, IL-8, IL-17, IL-22) in blood serum, stress hormones (ACTH, cortisol), cellular and humoral immunity condition (CD3 +, CD4 +, CD8 +, CD16 +, CD22 +, IgM and IgG levels) have been studied. RESULTS: Results: The clinical course and characteristic features of AP instrumental tests are extremely versatile as well as the depth of their present study is insufficient. Regardless of the disease duration period, we have detected in blood serum of AP patients probable changes in concentrations of stress-response mediators (decreased parameters of cellular immunity (CD3+, CD4+, CD8+ of T-lymphocytes, CD22+ fraction of B-lymphocytes and compensatory increased CD16+ of T-cells, cytokines - IL-1ß, IL-8, IL- 17, IL-22, stress hormones - cortisol, immunoglobulins IgM, IgG, and CIC), which indicate tension of their stress-induced mechanisms even despite occasional clinical stabilization of skin and articular process. We have offered and tested regiments to treat AP patients, which involve differential application within the integrated therapy of nonsteroidal anti-inflammatory medications (Arcoxia 30-60 mg 1 time daily / Naklofen Duo 75 mg daily), disease-modifying medications (Sulfasalazine ЕН from 500 mg to 2 g daily / Methotrexate 7.5-10 mg/week), lyophilised dialysate of leukocytes. CONCLUSION: Conclusions: The analysis of specific features of the AP clinical course and data of integrated studies allows identifying the probability of manifestation or persistence of the pathological psoriatic articular process. The improvement of AP patients diagnostics taking into account some indicators of the immune-endocrine system and specifics of the disease course contributed to the improved therapy and mended quality of life of patients.

The comparative immunogenicity of biologic therapy and its clinical relevance in psoriatic arthritis: a systematic review of the literature.

INTRODUCTION: Biologic agents have demonstrated efficacy in treating patients with psoriatic arthritis (PsA). Biologic agents also have an intrinsic capacity to induce an immune response in patients that could result in unwanted adverse events and/or treatment failure. AREAS COVERED: In this systematic literature review, the authors document the incidence of immune responses, primarily anti-drug antibodies (ADA), to the biologic therapeutic agents currently in clinical practice for the treatment of PsA. The authors discuss the importance of these responses with respect to clinical practice. EXPERT OPINION: Our evaluation of the published literature shows that the immune responses to the various biologic therapeutic agents currently being used to treat PsA are similar to those observed for these agents in other rheumatic diseases. Moreover, similar to observations in other rheumatic diseases, the incidence of ADA formation to biologic agents in patients with PsA is often decreased when patients are given concomitant treatment with disease-modifying anti-rheumatic drugs. These data strongly suggest that the immune response is a characteristic of the biologic agent. Using therapeutic drug monitoring may be an approach to assess the immune response to the agent and to mitigate the potential impact on efficacy and safety, and consequently optimize treatment.

Biologics in Inflammatory and Immunomediated Arthritis.

BACKGROUND: Biologic drugs, introduced in clinical practice almost twenty years ago, represent nowadays a prominent treatment option in patients with chronic inflammatory arthritis, such as Rheumatoid Arthritis, Psoriatic Arthritis and Spondyloarthritis, that include ankylosing spondylitis and non-radiographic axial spondyloarthritis. METHODS: Several compounds targeting different pathways have been marketed and approved for the treatment of inflammatory arthritis, with a significant impact on the clinical outcomes and the natural history of the diseases. RESULTS: There are currently seven classes of biologics that are available for the treatment of inflammatory arthritis, each inhibiting a different aspect of the immune-driven inflammatory pathway. They include: • Tumor Necrosis Factor (TNF) inhibitors (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol); • Interleukin-1 (IL-1) receptor antagonists (anakinra); • Interleukin-6 (IL-6) inhibition (tocilizumab); • Interleukin-12/23 (IL23) inhibition (ustekinumab); • Interleukin-17 (IL-17) inhibition (secukinumab); • B-cell inhibition (anti-CD20, rituximab); • T-cell costimulation inhibition (anti-CTLA-4, abatacept). CONCLUSION: In this review, we will focus on the role of biologic drugs in the treatment strategies for inflammatory arthritis.

Biologic Therapies for Autoimmune and Connective Tissue Diseases.

Biologic therapy continues to revolutionize the treatment of autoimmune disease, especially in rheumatology as the pathophysiology of both inflammation and autoimmune disease becomes better understood. These therapies are designed to dampen the response of the inflammatory cascades. Although the first biologic therapies were approved many years ago, expanding indications and new agents continue to challenge the traditional treatment strategies for rheumatic diseases. This article reviews the data supporting the current use of biologic therapies, including off-label indications, in a subset of rheumatic diseases including rheumatoid arthritis, lupus, inflammatory myositis, ankylosing spondylitis, psoriatic arthritis, vasculitis, and gout.

A Retrospective Cohort Study Comparing Utilization and Costs of Biologic Therapies and JAK Inhibitor Therapy Across Four Common Inflammatory Indications in Adult US Managed Care Patients.

INTRODUCTION: Biologic therapies are used to treat several inflammatory diseases, including rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Data from a commercial claims database were used to evaluate utilization and cost of biologic treatment for these conditions. METHODS: Data were obtained from the Optum Research Database. Patients were aged 18-63 years with diagnosis of moderate to severe RA, PsO, PsA, and/or AS and first (index) claim for biologics abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab, or ustekinumab or non-biologic tofacitinib between March 1, 2011 and February 28, 2013. One-year treatment costs were based on observed paid amounts and used to impute dosing. Treatment patterns (persistence, switching, discontinuing, restarting) were evaluated. RESULTS: Data from 20,159 patients were analyzed for index medications abatacept (n = 583), adalimumab (n = 6521), certolizumab pegol (n = 415), etanercept (n = 9116), golimumab (n = 231), infliximab (n = 1906), rituximab (n = 295), tocilizumab (n = 165), ustekinumab (n = 922), and tofacitinib (n = 5). For patients with RA only, costs were lowest for tofacitinib ($18,769), rituximab ($19,569), or abatacept ($21,877), and ranged from $23,682 to $30,269 for all other medications. For patients with PsO only, costs were lowest for adalimumab ($29,186), etanercept ($31,212), and infliximab ($32,409) compared with ustekinumab ($53,746). For patients with PsA only, costs were lowest for etanercept ($26,916), followed by golimumab ($27,987), adalimumab ($28,749), and infliximab ($31,974). Costs were lowest with etanercept for RA plus PsA ($25,477) and for PsO plus PsA ($29,376), and with golimumab for AS only ($24,225). Across indications, annual costs were $29,521, $27,488, and $28,672 for adalimumab, etanercept, and infliximab, respectively; persistence was greatest with infliximab (range 66-79%) compared with 11-59% for all other biologics. CONCLUSION: One-year treatment costs varied considerably between medications and indications. Some newly approved agents had lower costs but further research is needed to confirm these estimates as more patients are treated. FUNDING: Immunex (a wholly owned subsidiary of Amgen Inc.) and Wyeth (acquired by Pfizer).

Biologic Therapy in Immune Mediated Inflammatory Disease: Basic Science and Clinical Concepts.

During the last decades, the advent of biological therapies has revolutionized the management of several immune-mediated inflammatory disorders, as inflammatory bowel diseases, autoimmune arthritis and psoriasis, which significantly impact both quality of life and health care economics. Biological therapies currently available can be divided into two main categories: the tumor necrosis factor-α antagonists (infliximab, adalimumab, etanercept, golimumab, certolizumab pegol) and interleukin 12/23 monoclonal antibodies (ustekinumab). Biologics, reducing TNFα bioavailability or inhibiting proximal regulators of inflammatory cascade, represent an established therapeutic strategy of inflammatory autoimmune diseases, with remarkable efficacy and a safety profile that is extensively examined and monitored. The biology and the immunological effects of TNFα, IL-12, IL-23 and related signalling pathways are accurately summarized. The dosing regimens, methods of administration, pharmacodynamics profiles, and side effects of the currently licensed TNFα antagonists and IL12/IL23 inhibitor are discussed in detail.

Toward Treating to Target in Psoriatic Arthritis.

The concept "treat to target" in rheumatology was first developed for rheumatoid arthritis. A similar attempt to develop such an approach for spondyloarthritis was unsuccessful because the assessment tools and target of therapy had not been developed. In psoriatic arthritis (PsA), composite indices to assess disease activity, disease state, and responsiveness have been developed and can be used as targets. There are a number of definitions for remission, but none are widely accepted. However, a state of minimal disease activity has been defined. There is evidence now that the treat-to-target approach is feasible, using the minimal disease activity state as a target and devising a tight control approach, which is superior to standard of care. Further work will determine the best target and the best approach to reach it.

Adherence to biologic therapies and associated factors in rheumatoid arthritis, spondyloarthritis and psoriatic arthritis: a systematic literature review.

OBJECTIVES: To analyse the evidence on adherence to biologic therapies in rheumatoid arthris (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). METHODS: Systematic review of studies retrieved by a sensitive search strategy in MEDLINE database (1961 through March 2012). To be selected, studies had to include patients with RA, SpA, or PsA, treatment with intravenous or subcutaneous biologic therapies, and had to report on measures of adherence. By design, only randomised controlled trials (RCT) or high quality cohort studies with a control group were selected. RESULTS: A total of 24 studies were included, of which 12 reported results from national or local biologic registers, 9 were retrospective studies, 2 prospective studies, and only one was an RCT. Patients included were mostly women with diagnosis of RA or SpA and, less frequently, PsA. There was a great variability in the definition of adherence, measurement methods, and associated factors analysed. In general, adherence to etanercept was superior to that of other biologics, by the measures utilised. The main predictive factors - age, sex, comorbidity, baseline clinical condition, previous or concomitant use of DMARDs, anti-TNF in monotherapy or in combination with MTX - produced diverse, even divergent results across studies. CONCLUSIONS: There is a wide variability related to the adherence concept and its measurement, reflecting the complexity of the phenomenon. In order to draw more consistent conclusions about the relative value of predictive factors on adherence and persistence of biological therapy, larger controlled studies with better selection of variables and analysis of interactions are needed.

Golimumab, the newest TNF-α blocker, comes of age.

Golimumab, a fully human monoclonal antibody against tumour necrosis factor-α (TNF-α) is one of the newest biologics that has become available for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Following the initial randomised double-blind placebo-controlled clinical trials, which demonstrated the efficacy and safety of the drug in the context of a limited patient sample and a relatively short time frame, golimumab has been the focus of continuous investigation through the extensions of the above-mentioned trials, new clinical trials and registries of biologic drug use in daily clinical practice. The review of this data and their inclusion in meta-analyses and indirect comparisons across TNF-α blockers suggest that golimumab possesses similar properties regarding efficacy and safety as the older monoclonal anti-TNF-α antibodies. The novelty of golimumab is perhaps its dosing regimen, i.e. subcutaneous self-administration once monthly, which allows for the least disturbance in the life of patients.

Preclinical characterisation of the GM-CSF receptor as a therapeutic target in rheumatoid arthritis.

OBJECTIVE: Previous work has suggested that the granulocyte macrophage colony stimulating factor (GM-CSF)-GM-CSF receptor α axis (GM-CSFRα) may provide a new therapeutic target for the treatment of rheumatoid arthritis (RA). Therefore, we investigated the cellular expression of GM-CSFRα in RA synovial tissue and investigated the effects of anti-GM-CSFRα antibody treatment in vitro and in vivo in a preclinical model of RA. METHODS: We compared GM-CSFRα expression on macrophages positive for CD68 or CD163 on synovial biopsy samples from patients with RA or psoriatic arthritis (PsA) to disease controls. In addition, we studied the effects of CAM-3003, an anti-GM-CSFR antibody in a collagen induced arthritis model of RA in DBA/1 mice. The pharmacokinetic profile of CAM-3003 was studied in naïve CD1(ICR) mice (see online supplement) and used to interpret the results of the pharmacodynamic studies in BALB/c mice. RESULTS: GM-CSFRα was expressed by CD68 positive and CD163 positive macrophages in the synovium, and there was a significant increase in GM-CSFRα positive cells in patients in patients with RA as well as patients with PsA compared with patients with osteoarthritis and healthy controls. In the collagen induced arthritis model there was a dose dependent reduction of clinical arthritis scores and the number of F4/80 positive macrophages in the inflamed synovium after CAM-3003 treatment. In BALB/c mice CAM-3003 inhibited recombinant GM-CSF mediated margination of peripheral blood monocytes and neutrophils. CONCLUSIONS: The findings support the ongoing development of therapies aimed at interfering with GM-CSF or its receptor in various forms of arthritis, such as RA and PsA.

Continuous versus intermittent therapy for moderate-to-severe psoriasis.

Psoriasis is a chronic immune-mediated inflammatory disease of unknown etiology. Unlike other chronic inflammatory diseases receiving continuous treatment, psoriasis has traditionally been treated intermittently secondary to concern for cumulative toxicity of conventional systemic therapies. However, the development of targeted anti-inflammatory biologic agents allowed for continuous therapy for most patients. Herein, we review the literature for intermittent versus continuous use of widely available therapies for moderate-to-severe psoriasis: phototherapy, topical corticosteroids, conventional systemic therapies and biologic agents. These data support continuous treatment in biologic therapy, such as etanercept, adalimumab, infliximab, and ustekinumab. Intermittent therapy with biologic agents leads to decreased efficacy and sometimes increased side effects. When conventional systemic therapy is used continuously, it is more efficacious; however the data support intermittent use of methotrexate and cyclosporine due to cumulative toxicities. Psoriasis severity may wax and wane, but it is a chronic disease requiring continuous treatment for optimal control of inflammatory activity and to minimise cutaneous involvement.

[Indications and efficacy of biologics in inflammatory arthritis]. / L'apport et les indications des biothérapies dans les rhumatismes inflammatoires.

Major advances in our knowledge of the pathogenesis of inflammatory arthritis during the last 20 years, including the identification of precise targets of joint inflammation, led to the development of biologic targeted therapies. TNF inhibitors were the first such agents to be approved in rheumatoid arthritis, followed by ankylosing spondylitis and psoriatic arthritis. Later, rituximab, an anti-CD20 B lymphocyte antibody ; abatacept, which inhibits the T cell co-stimulatory CD28-CD80 pathway ; and tocilizumab, an interleukin-6 receptor inhibitor, were launched in rheumatoid arthritis. These biologics have dramatically changed the management and mid- to long-term outcomes of patients with rheumatoid arthritis and spondyloarthritis. Current therapeutic strategies are based on disease activity and severity. International societies such as EULAR and ASAS have published precise recommendations for routine management of these patients.

Adverse reactions during biological drug therapy in psoriasis:clinical series and a review of the literature.

AIM: Psoriasis is a chronic, inflammatory skin disorder, histologically characterized by epidermal hyperplasia, anomalous keratinocyte differentiation, angiogenesis, and by inflammatory cell infiltrate. Psoriasis has a significant impact on quality of life and is often associated with serious psychological effects. The use of biological agents is expanding worldwide as alternative treatment for chronic inflammatory diseases including psoriasis. The European Medicines Agency (EMEA) approved the use of Efalizumab, Etanercept, Infliximab and Adalimumab in the treatment of psoriasis on the basis of the positive findings obtained from well-designed clinical trials. The ongoing monitoring of tolerability and possible side-effects of these drugs has, however, recently lead to the EMEA suspending Efalizumab on the grounds that the possible risks of its use outweighed the benefits. METHODS: Fifty-four patients treated with the two classes of biological drug (Efalizumab and anti-TNF-α) were studied. The choice of biological drug therapy was conditioned by the extent and seriousness of the disease and by the presence of concomitant pathologies. RESULTS: Nineteen patients presented adverse reactions, of which 9 necessitated interruption in treatment (6 Efalizumab and 3 anti-TNF-α). CONCLUSION: This work reports the adverse reactions to these biological therapies found in our patients along with a review of the literature concerning adverse reactions in psoriasis treatment. From our experience and basing ourselves on the literature reporting studies conducted in large centres, we feel that it is indispensable to continue monitoring any reactions during biological drug treatment. In this way, there is more likelihood of preventing, where possible, or better managing any reactions linked to the use of these drugs.

Antibodies to human tissue transglutaminase and alterations of vitamin D metabolism in ankylosing spondylitis and psoriatic arthritis.

Both in ankylosing spondylitis (ASP) and psoriatic arthritis (PsA), osteopenia is present in one-third of women and men, whereas osteoporosis mainly affects men, even in their 30 s. Subclinical gut inflammation has been described in patients with AS or PsA. Joint involvement also occurs with other gastrointestinal diseases such as celiac disease. We tested the hypothesis, whether elevated serum levels of human anti-tissue-transglutaminase-IgA (htTG) are associated with changes in disease activity, vitamin D metabolism and bone mineral density (BMD) in patients with ASP and PsA. In a cross-sectional study, we evaluated both biochemical markers of bone turnover, BMD and htTG in 76 patients with ASP and 120 patients with PsA. A reduction of BMD in lumbar spine was determined both in ASP (42.7%) and in PsA (57.3%). Furthermore, a significantly higher prevalence of htTG was detected only in ASP (14/76). ASP patients with negative htTG status have significant higher 25-vitamin D3 levels. ASP patients with positive htTG status are younger. A positive htTG status entails the risk of a bad vitamin D supply, which should be considered in young patients since this constellation favors a reduction in bone density. The coincidence of ASP along with detection of htTG and clinically asymptomatic celiac disease as an accessory source of inflammation with a negative influence on the bone metabolism is also conceivable. Clinicians need to be aware of patients younger than 45 years with ASP, which have important implications for the correct treatment and vitamin D supplementation.

In vitro spontaneous osteoclastogenesis of human peripheral blood mononuclear cells is not crucially dependent on T lymphocytes.

OBJECTIVE: In vitro spontaneous osteoclastogenesis from peripheral blood mononuclear cells (PBMCs) is increased in diseases with excessive bone loss. The purpose of this study was to reassess the role of T lymphocytes in this process. METHODS: Fresh or cryopreserved PBMCs obtained from healthy subjects and from patients with rheumatoid arthritis, psoriatic arthritis, and non-psoriatic spondylarthritis were cultured at high density and stained for tartrate-resistant acid phosphatase (TRAP). Resorption of mineralized matrix was assessed by a dentin disc assay. CD14+ monocytes and CD3+ T cells were selected using magnetically labeled antibodies. RESULTS: Numerous multinucleated, TRAP+, dentin-resorbing osteoclasts developed spontaneously from fresh PBMCs from healthy individuals. This process was abrogated by T cell depletion and was restored by exogenous macrophage colony-stimulating factor (M-CSF) and RANKL, indicating the important role of T cells in spontaneous osteoclastogenesis in vitro. Using physiologic freezing and thawing as a model for the activation of PBMCs, spontaneous osteoclastogenesis was significantly increased in cryopreserved versus fresh cells. Under these conditions, spontaneous osteoclastogenesis was not dependent on T lymphocytes, since it was not influenced by T cell depletion and persisted in purified CD14+ cell cultures supplemented with M-CSF and RANKL. In contrast to studies with fresh PBMCs, spontaneous osteoclastogenesis under these conditions did not appear to be clearly different between healthy subjects and patients with arthritis. CONCLUSION: Spontaneous osteoclastogenesis in vitro is dependent on T lymphocytes or on the direct activation of monocytic cells, depending on the test conditions. This variability warrants better validation of the relevance of this functional test for in vivo osteoclastogenesis.

Apolipoprotein A-I and cholesterol in synovial fluid of patients with rheumatoid arthritis, psoriatic arthritis and osteoarthritis.

OBJECTIVE: To investigate lipid and apolipoprotein (Apo) levels in synovial fluid (SF) and serum of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and osteoarthritis (OA). METHODS: SF of 44 patients (14 RA, 14 PsA, 16 OA) was tested for Apo A-I, HDL-C, total cholesterol (TC), IL-1Beta, TNF-alpha, white blood cell count (WBC) and polymorphonucleate (PMN) percentage. Blood samples, collected simultaneously to the SF, were examined for Apo A-I, HDL-C, TC, TNF-alpha, serum amyloid A (SAA) and C-reactive protein (CRP). Thirty-three healthy donors served as a control group. RESULTS: Serum levels of Apo A-I, HDL-C and TC were higher in OA as compared with RA, PsA and the control group. The patients with inflammatory arthritis had lower serum levels of Apo A-I and HDL-C than did the controls. Apo A-I concentrations were higher in SF of RA patients, while PsA showed the highest concentration of TC, though not reaching statistical significance. A negative correlation was found between serum Apo A-I and synovial WBC (r=-0.48 p=0.002) and IL-1Beta (r=-0.42 p=0.016). There was a strong positive correlation between the Apo A-I SF/serum ratio and synovial WBC (r=0.73 p<0.001), IL-1Beta (r=0.68 p<0.001) and a weak, yet significant, correlation with serum CRP (r=0.49 p=0.002) and SAA (r=0.41 p=0.008). CONCLUSION: Our study confirms that in RA Apo A-I and TC levels are decreased in plasma and increased in SF, thus suggesting infiltration of HDL particles in the inflamed joint with inhibition of the local production of proinflammatory cytokines. On the other hand, it can be hypothesized that the sequestration of Apo A-I in the inflamed tissue may, in part, account for the reduction of circulating HDL and the excess cardiovascular risk in RA and PsA patients.

Immunological and clinical effects of alphacalcidol in patients with psoriatic arthropathy: results of an open, follow-up pilot study.

The aim of this study was to describe the effect of systemic alphacalcidol (1 OH vitamin D3) treatment on clinical and immunological parameters in patients with psoriatic arthropathy. Among the 19 patients investigated, 10 were treated with 0.25 microg oral alphacalcidol twice daily for 6 months, while 9 other patients served as controls. In the peripheral blood of the treated group but not in the controls, a statistically significant decrease was observed in the percentage of CD3/CD69-positive activated and CD8-positive interferon-gamma-producing T cells and in the serum level of interferon-gamma during the first 3 months and also in the clinical activity of the disease during the whole 6-month follow-up period. Our results show that systemic alphacalcidol treatment has an immunomodulatory effect on patients with psoriatic arthropathy. This effect is manifested by a short-term temporary decrease in type 1 immune responses and a continuous decrease in disease activity.