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PubMed1994

The genetics of psoriasis.

BACKGROUND AND DESIGN: Psoriasis is a member of a class of common, HLA-associated conditions in which disease susceptibility appears to be heritable. However, the mode of inheritance of these diseases has been difficult to define in simple mendelian terms. Psoriasis displays one of the strongest HLA associations of this class of diseases. However, only a small fraction of those who carry the implicated HLA susceptibility alleles develop disease, and it has proven difficult to demonstrate that the HLA associations observed are due to formal genetic linkage between the disease and the HLA locus. Although the role of environmental factors in psoriasis and these other diseases cannot be denied, the participation of additional genes, not necessarily linked to HLA, has long been suspected. OBSERVATIONS: Epidemiologic and immunogenetic data are reviewed and analyzed, which demonstrate that a predisposition to psoriasis is heritable, and which implicate genes of the HLA locus as necessary but not sufficient determinants of psoriasis. Recent developments in human genome research are described, which make possible a systematic search for additional genetic determinants of psoriasis, including those unlinked to HLA. CONCLUSIONS: As one of the most common, most heritable, and most highly HLA-associated examples of this class of HLA-associated diseases, psoriasis represents an ideal target for the application of this emerging genomic technology.

Adolescent↗
PubMed1996

The coexistence of psoriasis with lupus erythematosus and other photosensitive disorders.

The coexistence of psoriasis with LE or other photosensitive disorders is rare in our patient population, occurring in 0.69% of patients with psoriasis and 1.1% of those with LE. PMLE was the most common cause of photosensitivity in psoriatic patients without LE, occurring in 32%. Less common causes included drug-related photosensitivity (thiazides and thiazide derivatives in four of the five cases), PUVA reactions, and photocontact reactions. The Goeckerman regimen or UVB applied in a cautious, well-controlled atmosphere was generally well tolerated in this group, including patients with PMLE. Photosensitivity occurred in 50% of our patients with psoriasis and LE, and it was secondary to LE in 70% of cases. Most patients were female and had SLE. Psoriasis developed first in 55% of the cases. Studies that were useful for distinguishing photosensitive from nonphotosensitive patients with SLE included determination of antibodies to extractable nuclear antigens (67% versus 14%), double-stranded DNA (64% versus 9%), and skin biopsy for direct immunofluorescence (58% versus 27%). Occasional patients have features suggestive of photosensitivity with or without signs or symptoms of LE. These patients may have atypical psoriatic plaques occasionally yielding routine histology diagnostic of psoriasis with direct immuno-fluorescence results suggestive of lupus. Frequently, connective tissue serology findings are positive, and affected patients require close follow-up for the development of LE. In patients with psoriasis and suspected photosensitivity, we recommend a careful history and examination, skin biopsy for routine histology and direct immunofluorescence, blood tests including determination of antibodies to antinuclear antibodies (Hep-2 substrate if negative on routine substrate), extractable nuclear antigens, and double-stranded DNA, and phototesting when indicated. Large-scale prospective studies are required before the most appropriate therapy for patients with psoriasis and LE can be recommended.

Adolescent↗
PubMed1996

Alternative therapies commonly used within a population of patients with psoriasis.

Alternative therapies are known to be employed by dermatology patients. This study investigates the use of alternative medical treatments for psoriasis and the sociodemographic variables, conventional medical treatment, and psoriasis disease severity. Our study population consisted of 578 university dermatology clinic patients with psoriasis and data was analyzed from 317 (55 percent) questionnaire respondents. The majority of our sample were women (57 percent) and nonwhites represented 8 percent of our sample. Psoriasis severity was measured using the validated Self-Administered Psoriasis Area and Severity Index. Alternative medicine was used by 62 percent of respondents. Excluding sunlight and nonprescription tanning equipment, 51 percent used one or more of the remaining alternative therapeutic modalities. The psoriasis severity was worse in those who had tried herbal remedies, vitamin therapy, and dietary manipulation. With the exception of vitamin therapy, we observed no association between the intensity of conventional medical treatment and alternative treatment. The present or prior use of herbal remedies was correlated with the use of vitamin therapy and sunbathing, and dietary interventions were significantly correlated with vitamin therapy. Of the 113 (36 percent) who had used nonprescription tanning equipment for their psoriasis, 68 percent believed this modality was effective. We found that alternative medical therapies were widely utilized by subjects participating in this study. Clinicians need to continue to be aware of nonallopathic remedies employed by their patients to discover useful information about future therapies and to monitor for adverse effects.

Adolescent↗
PubMed1996

Both psoriasis and benign migratory glossitis are associated with HLA-Cw6.

This study was undertaken to investigate human leucocyte antigen (HLA) associations with benign migratory glossitis and psoriasis in Brazilian patients and particularly to determine whether benign migratory glossitis is also associated with HLA-Cw6, the classical association observed in psoriasis. The results showed a highly significant association of Cw6 with both psoriasis and benign migratory glossitis, with this antigen being present in 59.1% of the patients with psoriasis, in 43.8% of the patients with benign migratory glossitis, and in only 12.6% of the controls. Other significant positive associations, although at a lower significance level, were with B13, both in psoriasis and in benign migratory glossitis, and with B17, only in psoriasis. To our knowledge, this is the first report on the association of Cw6 with benign migratory glossitis. We believe that this finding reinforces the concept of a pathogenetic relationship between benign migratory glossitis and psoriasis.

Female↗
PubMedDate not supplied

Clinical analysis of staphylococcal superantigen hyper-reactive patients with psoriasis vulgaris.

It has been recently hypothesized that superantigens, which stimulate T cells expressing particular T cell receptor Vbeta chain gene segments, play a precipitating or aggravating role in psoriasis. In this study, we investigated the peripheral blood mononuclear cell (PBMC) response of patients with psoriasis vulgaris to staphylococcal superantigens (staphylococcal enterotoxin A (SEA), SEB, and SEC1) and its relationship to clinical and laboratory findings. Cytokine secretion was assessed by ELISA in the supernatants of the cultured PBMCs stimulated with SEB. Results of 3H-TdR uptake showed that the PBMCs' response against SEB in patients with psoriasis vulgaris (34,468 +/- 6,455) (mean DPM SD) was significantly higher than that of normal subjects (22,756 +/- 5,780) (p < 0.005). The stimulation index (SI) of patients with psoriasis vulgaris (n = 37) (63.9 +/- 55) was significantly higher than that of normal subjects (n = 24) (26.0 +/- 23) (p < 0.005) and patients with atopic dermatitis (n = 10) (40.7 +/- 30) (p < 0.05). Similar results were obtained in response to SEA and SEC1. SI weakly correlated with the psoriasis area and severity index (PASI) score (r = 0.62) and the serum interleukin-6 (IL-6) concentration (r = 0.45). IL-2 and tumor necrosis factor (TNF-alpha) were secreted at a significantly increased level by PBMCs from psoriatic patients on incubation with SEB, after a 3 day culture period. A higher level of IL-6 was released by PBMCs stimulated with SEB in psoriatic patients than normal controls, however, the difference was not significant. These results raise the possibility that monocytes, as well as T cells, are markedly activated by staphylococcal superantigen in patients with psoriasis vulgaris, which may play a role in the triggering or aggravating of psoriasis mediated by secreted cytokines.

Case-Control Studies↗
PubMed2003

Pathophysiology of psoriasis: coping endotoxins with bile acid therapy.

The authors have tested the hypothesis that the deficiency of bile acids and the consequent endotoxin translocation might play a role in the pathogenesis of psoriasis. Under normal conditions the bile acids act as detergents (physico-chemical defense) and can protect the body against enteric endotoxins by splitting them into nontoxic fragments and thus preventing the consequent release of cytokines [Persp. Biol. Med. 21 (1977) 70]. A total of 800 psoriasis patients participated in the study and 551 were treated with oral bile acid (dehydrocholic acid) supplementation for 1-8 weeks. The efficacy of the treatment was evaluated clinically and also by means of the Psoriasis Area Severity Index (PASI score). During this treatment, 434 patients (78.8%) became asymptomatic. Of 249 psoriatics receiving the conventional therapy, only 62 (24.9%) showed clinical recovery during the same period of time (P<0.05). The curative effect of bile acid supplementation was more pronounced in the acute form of psoriasis (95.1% of the patients became asymptomatic). Two years later, 319 out of the 551 acute and chronic psoriasis patients treated with bile acid (57.9%) were asymptomatic, compared to only 15 out of the 249 patients (6.0%) receiving the conventional treatment (P<0.05). At the end of the 2-year follow-up, only 10 out of 139 acute psoriasis patients (7.2%) receiving the conventional therapy and 147 out of 184 bile acid treated patients (79.9%) were asymptomatic (P<0.01).To conclude, the results obtained suggest that psoriasis can be treated with success by oral bile acid supplementation presumably affecting the microflora and endotoxins released and their uptake in the gut.

Journal Article↗
PubMed1994

Immunohistochemical markers for arthritis in psoriasis.

OBJECTIVES: To examine the immunohistological features in the involved skin of patients with psoriatic arthritis (PA) (n = 15), compared with those in involved skin from patients with psoriasis but no arthritis (n = 5), and with a group with normal skin (n = 4), to identify markers for arthritis in psoriasis. METHODS: Skin was obtained from patients by 6 mm punch biopsy and normal skin was provided by the department of plastic surgery. Samples were stained with monoclonal antibodies against T cells (CD3, CD8, CD4, CD45Ro), B cells (CD20), macrophages (mac387), vascular endothelium (FVIII-related antigen) and a Langerhan's cell marker (p155). The number of cells/vessels staining with each monoclonal antibody was calculated and serial sections of skin were examined to estimate the presence of DR+ keratinocytes. RESULTS: There were significantly more CD45Ro T-cells and blood vessels in patients with psoriatic arthritis compared with both psoriasis alone, and with normal controls (p < 0.02). While B-cells were not seen in psoriasis without arthritis or in normal skin, a small but significant number were observed in PA (p < 0.02). Furthermore, while DR+ keratinocytes were present in both psoriatic arthritis and psoriasis skin, there were significantly more DR+ cells in the psoriatic arthritis epidermis compared with psoriasis alone (p < 0.02). CONCLUSIONS: This study suggests that increased numbers of CD45Ro T-cells, greater vascularity, the presence of B-cells, and increased numbers of DR+ epidermal cells are markers for arthritis in patients with psoriasis.

Adult↗
PubMed1998

Psoriasis.

Psoriasis is an inflammatory disorder of the skin that involves complex interactions between the dermis and epidermis. There are several forms of psoriasis, the most common being plaque type psoriasis. Other forms include guttate, pustular and erythrodermic psoriasis. Both the skin and joints are affected in this disease. Psoriasis ranges in severity from a few small plaques to involvement of the entire cutaneous surface. Therapy of psoriasis depends on the location, type and severity of the disease. Treatments include a wide array of topical medications including tars, anthralin, topical corticosteroids, vitamin D(3) analogs, retinoids and over-the-counter preparations. Phototherapy with ultraviolet B and PUVA are used for more widespread involvement. Common systemic therapies include methotrexate, retinoids and cyclosporin. This article will review the pathogenesis and clinical features of psoriasis, as well as current and future therapies.

Journal Article↗
PubMedDate not supplied

Clinical analysis of 48 cases of inverse psoriasis: a hospital-based study.

Inverse psoriasis, rare in clinical practice, refers to psoriasis only or mainly occurring at flexural sites, such as the axilla, antecubital fossae, popliteal fossae, and inguinal creases. It is also known as flexural psoriasis. With a total collection of psoriatic cases from September 2002 to December 2003 at Xijing hospital, we made a retrospective analysis of the disease history, clinical characteristics, and treatment of the patients affected with inverse psoriasis. The results showed that the major clinical manifestations of inverse psoriasis were sharply demarcated erythematous plaques with varying degrees of infiltration and minimal or no scales. Affected areas often involve the groin, axilla, genitals, and umbilicus. The disease responds well to the narrow band UVB therapy. Compared with common psoriasis, inverse psoriasis has similar and unique characteristics in terms of the affected areas, clinical symptoms, and responses to the treatment.

Adolescent↗
PubMed2006

A randomized, multicenter, double-blind, placebo-controlled phase 2 trial of ISA247 in patients with chronic plaque psoriasis.

BACKGROUND: Use of current oral calcineurin inhibitors for the treatment of psoriasis is limited by toxicity. OBJECTIVE: Evaluate the safety and efficacy of ISA247, a new oral calcineurin inhibitor, in plaque psoriasis patients. METHODS: This 12-week, randomized, double-blind, placebo-controlled, parallel-group study included 201 plaque psoriasis patients with > or = 10% body surface area involvement. Patients were randomized to placebo, ISA247 0.5 mg/kg/d, and ISA247 1.5 mg/kg/d groups. End points included a 2-point reduction in the Static Global Assessment score and a 75% reduction in the Psoriasis Area and Severity Index. RESULTS: A 2-point SGA reduction was achieved in 0% (placebo), 15.6% (0.5 mg/kg/d), and 45.1% (1.5 mg/kg/d) (P < .0001). A 75% reduction in the Psoriasis Area and Severity Index was achieved in 0% (placebo), 18.2% (0.5 mg/kg/d), and 66.7% (1.5 mg/kg/day) (P < .0001). While serum creatinine increased in patients treated with ISA247 1.5 mg/kg/d, it remained within the normal range. LIMITATIONS: Longer-term studies are needed to evaluate the effect of ISA247 on renal function. CONCLUSION: ISA247 appears safe and effective for treating moderate to severe psoriasis.

Adolescent↗
PubMed1999

The MICA-A9 triplet repeat polymorphism in the transmembrane region confers additional susceptibility to the development of psoriatic arthritis and is independent of the association of Cw*0602 in psoriasis.

OBJECTIVE: To investigate the relative contribution of HLA antigens in the susceptibility to psoriasis and to localize additional genetic factors involved in psoriatic arthritis (PsA). METHODS: DNA from 45 patients with psoriasis, 65 with PsA, and 177 healthy control subjects was examined by polymerase chain reaction (PCR) using sequence-specific oligonucleotide probes to determine HLA-C. To examine whether MICA (class I major histocompatibility complex chain-related gene A) confers additional susceptibility, trinucleotide repeat polymorphism in the transmembrane region of the MICA gene was investigated by radioactive PCR. Further analysis of MICA was made by PCR-single-strand conformational polymorphism to determine the allelic variant corresponding to MICA transmembrane polymorphism. RESULTS: Our results reveal new findings: 1) the frequency of the Cw*0602 allele was significantly increased in both patient groups: psoriasis (corrected P [Pcorr] < 10(-5), relative risk [RR] 6.2), PsA (Pcorr < 10(-6), RR 6.3), 2) the trinucleotide repeat polymorphism MICA-A9 was present at a significantly higher frequency in PsA patients (Pcorr < 0.00035, RR 3.2), whereas a similar distribution was found in both the control and psoriasis population, 3) this polymorphism corresponds to the MICA-002 allele and was found to be overrepresented in patients with the polyarticular form (Pcorr < 0.0008, RR 9.35), 4) the increase in MICA-A9 in PsA patients is independent of linkage disequilibrium with Cw*0602, 5) this allele confers additional relative risk (RR 3.27, etiologic fraction 0.44; etiologic fraction is the proportion of disease cases among the total population that are attributable to 1 allele when the relative risk is > 1) in PsA patients who carry Cw*0602. CONCLUSION: The data obtained in this study are consistent with the polygenic inheritance of psoriasis. Cw*0602 appears to be the stronger genetic susceptibility factor for psoriasis. Independent of the HLA-C association, MICA-A9 polymorphism corresponding to the MICA-002 allele is a possible candidate gene for the development of PsA.

Adult↗
PubMed2004

High frequency of cholestasis in generalized pustular psoriasis: Evidence for neutrophilic involvement of the biliary tract.

Generalized pustular psoriasis is a rare form of psoriasis that is sometimes associated with extracutaneous manifestations. Evidence for biliary involvement has been suggested in isolated cases. We investigated the prevalence and nature of liver abnormalities occurring in this disease. Twenty-two patients consecutively admitted for generalized pustular psoriasis who underwent liver biological tests at the time of the attack and during the following weeks were included. Twenty patients (90%) had at least one abnormal biological liver parameter. Eleven patients (50%) had pronounced abnormalities: jaundice (4/22), gammaglutamyl transferase higher than 5 times the normal value (10/22), alkaline phosphatase higher than twice the normal value (7/22), and/or aminotransferases higher than 3 times the normal value (7/22). These abnormalities returned to normal range at the time of remission of pustular psoriasis, suggesting that severe liver abnormalities could be associated with severe cutaneous disease. Neutrophilic cholangitis was observed on liver biopsy. Persistent magnetic resonance cholangiopancreatography features similar to those observed in sclerosing cholangitis were found in 3 of the 4 patients studied. No causal factor other than pustular psoriasis could be identified. In conclusion, our results demonstrate the high frequency of liver abnormalities in patients with generalized pustular psoriasis. Biliary involvement related to neutrophilic cholangitis should be added to the spectrum of extracutaneous manifestations of this disease, and physicians should be aware of such a complication.

Adult↗
PubMed1987

Neutrophil locomotion and serum chemotactic and chemokinetic activities in pustulosis palmoplantaris compared with psoriasis.

Twenty patients with palmoplantar pustulosis (PPP) and 21 patients with psoriasis were compared with respect to the chemotactic response and random migration of their neutrophils (PMNs) and to the chemotactic and chemokinetic activities of their serum. The Boyden chamber technique was used. Compared with the reference group, the PPP neutrophils showed a significant decrease in random migration (p = 0.036) and chemotactic response to casein (p = 0.031), but not to zymosan-activated serum. The psoriasis PMNs had normal chemotactic response, but decreased random migration (p = 0.001). The chemokinetic effects of serum from PPP and psoriatic patients on normal neutrophils were increased (for PPP, p = 0.019 and for psoriasis p = 0.024). The chemokinetic activity of the heated sera was decreased and inversely correlated to the serum level of IgA in both disorders (PPP, p = 0.021; psoriasis, p = 0.013). The chemotactic activity of serum on normal PMNs was decreased in both conditions (PPP, p = 0.001; psoriasis, p = 0.047); this was due to the presence of chemotactic factor inhibitors in 34% of the sera. It seems likely that the high chemokinetic effect of serum both from the PPP and from the psoriasis patients compensates for the slightly low or normal migratory activity of neutrophils from these patients.

Adolescent↗
PubMed1984

Psoriasis and arthritis. III. A cross-sectional comparative study of patients with "psoriatic arthritis" and seronegative and seropositive polyarthritis: radiological and HLA aspects.

In a group of patients with seronegative polyarthritis and psoriasis, the radiological features and the incidence of histocompatibility antigens were compared with those of a group of patients with seronegative polyarthritis but not psoriasis. No radiological criteria proved to be characteristic of psoriatic arthritis. In the group of patients with seronegative polyarthritis and psoriasis, erosions of the distal interphalangeal (DIP) joints were seen more frequently and were more severe than in the group of patients with seronegative arthritis without psoriasis. For the group of patients with seronegative polyarthritis and psoriasis, correlation was found between psoriatic nail lesions and erosions of the DIP joints, but this correlation was not found between the nail involvement and erosion of the adjacent DIP joint. No significant differences were found for the incidence of histocompatibility antigens between patients with seronegative polyarthritis with or without psoriasis. However, differences were found between these two groups and either the seropositive polyarthritis group or blood bank donors.

Adult↗
PubMed1986

Decreased extracellular release of granule enzymes from in vitro-stimulated polymorphonuclear leukocytes in guttate psoriasis.

In vitro degranulation of polymorphonuclear leukocytes, which were stimulated either with synthetic chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine, FMLP) or with C3b-opsonized zymosan as a promotor of phagocytosis, was studied in 66 patients with psoriasis, 18 lesion-free psoriatics, 18 healthy subjects, and 14 other dermatological disorder controls. Stimulated release of lysozyme (from specific granules and azurophil granules) and beta-glucuronidase (from azurophil granules) in the presence of both FMLP and serum-activated zymosan was markedly reduced in patients with actively spreading guttate psoriatic lesions, in whom relapse of lesions lasted for less than 1 month and papules involved about 13-25% of skin surface. In contrast, stimulated degranulation was within normal range in active plaque psoriasis, stationary plaque psoriasis, symptomless psoriatics, and patients with disseminated eczema. Spontaneous release of lysozyme and beta-glucuronidase (background) was found to be not different in all groups studied; however, patients with active guttate psoriasis had significantly lower total lysozyme activity than those with active and stationary plaque psoriasis as well as psoriatics in the remission. These data are in favor of in vivo activation of neutrophils in active guttate psoriasis by some factors related to the early relapse of the lesions. This results in a possible combination of the following phenomena: (1) in vivo partial degranulation of neutrophils; (2) induction of "unresponsiveness state" of these cells to subsequent in vitro stimulation; and/or (3) migration of highly responsive neutrophils to skin lesions, which leaves in the circulation the subpopulation less reactive to chemotactic and phagocytic stimuli.

Cells, Cultured↗
PubMed1996

Immunogenetic profile of psoriasis vulgaris: association with haplotypes A2,B13,Cw6,DR7,DQA1*0201 and A1,B17,Cw6,DR7,DQA1*0201.

Psoriasis vulgaris is a skin disease with an immunological and genetic background present in 1-3% of the population. We studied the genetic susceptibility to psoriasis vulgaris in Finns with serological HLA typing and genomic HLA class II typing of the DQ and DP loci to evaluate the risk of developing psoriasis. The haplotypes most frequently distinguishing between psoriatics and controls were those that carried Cw6 (P < 10(-8)), DQA1*0201 (P = 9.3 x 10(-6)) and DR7 (P = 3.9 x 10(-5)). The two most frequent marker haplotypes were A2,B13,Cw6,DR7, DQA1*0201 and A1,B17,Cw6,DR7,DQA1*0201, which were not found among the control subjects. A deficit of haplotype B8,DR3,DQ2 (2 out of 124 in the patients versus 15 out of 106 in the controls, P = 1.5 x 10(-4)) was found, and this was in accordance with a slightly decreased frequency of DQA1*0501 (P = 3.1 x 10(-2)), which was usually linked with this haplotype. These results stimulate the research for a genetic resistance factor in psoriasis. Thus, this report sheds further light on the immunogenetic background of psoriasis in Finland. We conclude that the inheritance of psoriasis has a polygenic mode, in which the Cw6,DR7,DQA1*0201 combination seems to be important (P = 7.5 x 10(-7), relative risk 24.4, aetiological factor 0.29).

Adult↗
PubMed1996

Adhesion molecules and IL-1 costimulate T lymphocytes in the autologous MECLR in psoriasis.

Membrane molecules such as CD36 (OKM5), intercellular adhesion molecule-1 (ICAM-1, CD54), gamma interferon-induced protein 10 (gamma-IP10) and IL-1 are induced and/or upregulated in psoriatic epidermis. These molecules have important accessory, trafficking or signalling functions in the immune system and also play a role in the pathophysiology of psoriasis. The relevance of adhesion molecules, CD36 and epidermal IL-1 in psoriasis was studied in vitro in the autologous mixed epidermal cell - T lymphocyte reaction (MECLR). Their level of expression was quantitated in epidermal cell suspensions (ECS) from patients with psoriasis and their function was assessed by blocking with specific mAbs and antisera or by depleting CD36+ cells from the ECS prior to the MECLR. ECS from psoriatic lesions contained increased numbers of CD36+ (23 +/- 12%), ICAM-1(+) (31 +/- 14%) and IL-1(+) (57 +/- 21%) cells. The autologous MECLR was inhibited in samples from all patients by mAb to CD2 (LFA-2), CD11a (LFA-1alpha), CD18 (LFA-1beta), ICAM-1, CD58 (LFA-3) and an antiserum to IL-1beta. Thus, adhesion molecules facilitate inflammation in psoriasis not only via adhesion and recruitment of T lymphocyte in psoriatic lesions, but also via activation of T cells. Furthermore CD36 molecules on psoriatic epidermal cells do not costimulate autologous T lymphocytes in psoriasis. The observed costimulatory function of IL-1beta in the MECLR emphasizes its relevance in psoriasis.

Antibodies, Monoclonal↗
PubMedDate not supplied

Pharmacokinetics of IL-18 binding protein in healthy volunteers and subjects with rheumatoid arthritis or plaque psoriasis.

IL-18 binding protein (BP) neutralizes the activity of IL-18, a cytokine implicated in psoriasis and rheumatoid arthritis (RA). We investigated the pharmacokinetics, pharmacodynamics and safety of recombinant human IL-18 BP (r-hIL-18 BP) in healthy volunteers and subjects with psoriasis or RA in four phase I studies. A) Healthy volunteers (n = 24) were randomised to receive a single subcutaneous (sc) injection of r-hIL-18 BP (20, 70, 210 or 350 mg) or placebo. B) Healthy volunteers (n = 10) were randomised to receive six sc injections of r-hIL-18 BP (35 or 175 mg, 48 h between injections) or placebo. C) Subjects with moderate-to-severe plaque psoriasis (n = 35) were randomised to receive r-hIL-18 BP (20, 160 or 320 mg, sc tiw) or placebo for 6 weeks. D) Subjects with active, moderate-to-severe RA (n = 36) were randomised to receive r-hIL-18 BP (20, 80, 160 mg, sc tiw) or placebo for 6 weeks. Pharmacokinetics, pharmacodynamics and safety were assessed in all four studies. r-hIL-18 BP showed a dose-dependent pharmacokinetic profile, with a peak serum concentration of 6-48 hours. With repeated sc injections tiw, a steady state was achieved in 1-2 weeks among subjects with psoriasis or RA. The majority of adverse events were mild or moderate in severity. Injection site reactions were the most frequently reported event in subjects with psoriasis or RA. r-hIL-18 BP displays dose-dependent pharmacokinetics, has a favourable safety profile and is well-tolerated in healthy volunteers and in subjects with moderate-to-severe plaque psoriasis or active, moderate-to-severe RA.

Adolescent↗