-
F R Ali,
A Barton,
R L I Smith,
J Bowes,
E Flynn,
M Mangino,
V Bataille,
J P Foerster,
J Worthington,
C E M Griffiths, R B Warren
[show abstract]
[hide abstract]
ABSTRACT: Phenotypically diverse autoimmune conditions share common genetic susceptibility loci and underlying molecular pathways. We therefore investigated 18 single nucleotide polymorphisms, previously confirmed as being associated with rheumatoid arthritis (RA), in a UK cohort of 623 patients with early-onset psoriasis (presenting before age 40y) comparing with 2662 control subjects. Our findings confirm the association of early-onset psoriasis with REL (rs13031237, p=0.0027). The minor allele of REL had opposing effects upon susceptibility to disease in psoriasis and RA patients. Similar exploration of additional autoimmune loci and fine-mapping of such regions may provide further insight into the genetics and molecular pathophysiology of psoriasis.
British Journal of Dermatology 10/2012; · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Psoriatic arthritis remains a common cause of morbidity in patients with psoriasis. Little is known about the natural history of the disease and dermatologists do not consistently screen for its presence. We describe a patient with severe psoriasis where long-term biologic therapy with a tumour necrosis factor inhibitor was interrupted for clinical reasons, leading to a rapidly evolving axial spondyloarthritis and oligoarthritis. This unusual presentation of psoriatic arthritis may reflect masking of the disease by long-term treatment with a tumour necrosis factor inhibitor. We advocate the use of screening for psoriatic arthritis, including before and during treatment with biologic therapies.
Journal of Dermatological Treatment 07/2012; · 1.23 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The British Association of Dermatologists (BAD) established a web-based pharmacovigilance register to assess the long-term safety of biologics prescribed for patients with severe psoriasis in September 2007. The BAD Biologic Interventions Register (BADBIR) also participates in the network of European psoriasis biologics registers (Psonet).
This prospective observational cohort study compares adult patients with psoriasis treated with biologics vs. a comparator group exposed to conventional systemic therapies.
Following baseline data acquisition, clinicians record changes in therapy, disease activity and adverse events for 5years (6-monthly for 3years, then annually thereafter). Patient details are flagged lifelong on the National Health Service Information Centre system to capture occurrence of malignancy or death. Primary study endpoints include malignancy, infection, serious adverse events and death. Collection of long-term effectiveness data is a subsidiary aim.
By November 2011, the number of dermatology centres actively recruiting across the U.K. and Republic of Ireland had risen to 108 and a further 37 were actively engaged in the set-up process. Of the 3176 patients enrolled in the study to date, 2193 were registered within the biologic cohort and 983 in the conventional systemic (nonbiologic-exposed) cohort.
A robust, high-quality, web-based register of biologic and conventional therapy for psoriasis has been established in the U.K. This is the largest project undertaken by the BAD. The data it will provide over the coming years will be invaluable to the safe use of biologics in clinical practice. A U.K.-wide dermatology clinical research network has been established that provides a framework for future studies in other diseases.
British Journal of Dermatology 03/2012; 166(3):545-54. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The era of genome-wide association studies has revolutionized the search for genetic susceptibility loci in complex genetic conditions such as psoriasis. There are currently 16 loci with confirmed evidence for association with psoriasis susceptibility but there is the potential for more to be discovered as the genetic heritability of the disease has not yet been fully explained. Many of the associated loci overlap with those for psoriatic arthritis. In contrast to psoriasis susceptibility, few studies have been performed to identify predictors of drug response in psoriasis. As large-scale collaborations and registries for psoriasis and psoriatic arthritis are established, it is likely that a genome-wide approach may be used as a more effective method of searching for genetic predictors of treatment response. However, candidate gene studies will still have a role; for example, it is likely that some disease susceptibility genes will also be markers of treatment response, based on evidence from other diseases. This review summarizes recent advances in investigating the role genetics plays in psoriasis susceptibility and contrasts these to advances made in psoriatic arthritis. Further, it describes the genetics of treatment response in the two diseases and indicates how susceptibility loci could be used to identify drug response in the future.
British Journal of Dermatology 02/2012; 166(3):474 - 482. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The era of genome-wide association studies has revolutionized the search for genetic susceptibility loci in complex genetic conditions such as psoriasis. There are currently 16 loci with confirmed evidence for association with psoriasis susceptibility but there is the potential for more to be discovered as the genetic heritability of the disease has not yet been fully explained. Many of the associated loci overlap with those for psoriatic arthritis. In contrast to psoriasis susceptibility, few studies have been performed to identify predictors of drug response in psoriasis. As large-scale collaborations and registries for psoriasis and psoriatic arthritis are established, it is likely that a genome-wide approach may be used as a more effective method of searching for genetic predictors of treatment response. However, candidate gene studies will still have a role; for example, it is likely that some disease susceptibility genes will also be markers of treatment response, based on evidence from other diseases. This review summarizes recent advances in investigating the role genetics plays in psoriasis susceptibility and contrasts these to advances made in psoriatic arthritis. Further, it describes the genetics of treatment response in the two diseases and indicates how susceptibility loci could be used to identify drug response in the future.
British Journal of Dermatology 11/2011; 166(3):474-82. · 3.67 Impact Factor
-
R B Warren
British Journal of Dermatology 11/2011; 165(5):929. · 3.67 Impact Factor
-
P M Laws,
A M Downs,
R Parslew,
B Dever,
C H Smith,
J N Barker,
B Moriarty,
R Murphy,
B Kirby,
A D Burden,
S McBride,
A V Anstey,
S O'Shea,
N Ralph,
C Buckley,
C E M Griffiths, R B Warren
[show abstract]
[hide abstract]
ABSTRACT: There are limited data on the use of ustekinumab outside of clinical trials.
To assess the efficacy and safety of ustekinumab in patients with severe psoriasis attending 10 dermatology centres in the U.K. and Ireland.
A retrospective case-note review of 129 patients with psoriasis treated with ustekinumab.
Baseline Psoriasis Area and Severity Index (PASI) was 22·9±10·1 (mean±SD). After 16weeks of treatment with ustekinumab PASI 75 (75% reduction in PASI) was observed in 63·0% (n=80/127) of patients, although four patients required concomitant therapy at the 16-week time point. Previous biologic use did show a small, non-significant trend towards treatment failure. A PASI 75 response was seen in 29·4% (n=5/17) of individuals weighing 90-100kg and treated with the standard 45mg ustekinumab dose compared with PASI 75 of 70·3%, 71·4%, 75·0% and 55·6% for weight groups <80, 80-90, 100-110 and >110kg, respectively (P=0·024). Ustekinumab therapy was well tolerated; serious adverse events were observed in 2·3% (n=3/129) of patients.
Ustekinumab is a novel biologic agent for psoriasis. When used in everyday clinical practice it demonstrates high levels of short-term therapeutic efficacy with an acceptable short-term safety profile.
British Journal of Dermatology 09/2011; 166(1):189-95. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Even though psoriasis is a common skin disorder, reports of it involving the oral cavity are exceedingly rare, with less than 100 publications in the literature. Biopsy-proven oral psoriasis has been reported in the oral medical literature, but the commonest oral mucosal findings in most studies are associated non-specific features including fissured and geographic tongue. Case series on this entity have not provided any definitive data to support its existence. From the evidence available to date, it is still unclear if oral psoriasis is a distinct entity or if, indeed, it exists.
Archives for Dermatological Research 09/2011; 304(1):1-5. · 2.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This review summarizes key clinical findings from 5 guidelines and 21 systematic reviews on psoriasis published or indexed in the period November 2009 to October 2010. The highlights include the British Association of Dermatologists guidelines on the use of biological interventions in psoriasis, and guidelines on the efficacy and use of acitretin. Biological therapies were reviewed for use in specific patient groups (such as those with hepatitis C) and from a health-economics perspective. Another systematic review focused on outcome measures used to assess the severity of psoriasis. Finally, comorbidities including cardiovascular risk were the topic of four systematic reviews.
Clinical and Experimental Dermatology 07/2011; 36(6):585-9; quiz 588-9. · 1.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Psoriasis is associated with significant physical, psychological, social and economic burden, the cumulative effect of which may result in failure to achieve 'full life potential' in some patients, termed 'cumulative life course impairment' (CLCI). In this concept, the burden of stigmatization, and physical and psychological comorbidities (risk factors for cumulative impairment) and coping strategies and external factors (having potential moderating effects), interact to cause lifetime impairment. Components of CLCI are supported by cross-sectional data; however, the cumulative nature of impairment in patients with psoriasis is not yet established. Nonetheless, CLCI makes intuitive sense to many dermatologists who recognize the cumulative impact of psoriasis on the lives of some patients. This supplement explores the causes and mechanisms of CLCI qualitatively by presenting cases which are representative of typical patients with moderate-to-severe psoriasis. These cases demonstrate the effect of psoriasis in influencing major life-changing decisions and altering the course of patients' lives, preventing patients from attaining their life goals, pursuing their chosen career, gaining a desired educational level, developing social relationships, gaining full pleasure from family life or having children. All these patients believe that their lives would have taken a different course had they not had psoriasis. Additional research to determine how CLCI occurs and to identify the risk factors for cumulative impairment is required. Understanding the key risk factors for CLCI may help physicians identify patients who are more vulnerable to the cumulative impact of psoriasis, resulting in more appropriate treatment decisions earlier in the disease course.
British Journal of Dermatology 05/2011; 164 Suppl 1:1-14. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Many autoimmune diseases share common susceptibility loci suggesting similar underlying cellular mechanisms involved in disease expression.
The purpose of this investigation was to study 21 genetic variants in 14 genes that are confirmed autoimmune loci in a cohort of patients with early-onset psoriasis.
Patients with early-onset psoriasis (n = 750) and controls (n = 3531) were genotyped using the Sequenom(®) MassArray™ iPLEX Gold platform.
We found strong evidence of association with two variants in the IL2/IL21 (rs6822844, genotypic P = 3·3 × 10(-4) ; rs2069778, genotypic P = 7·86 × 10(-4)) region.
The findings, although requiring replication, suggest that IL2/IL21 may play a key role in the pathogenesis of psoriasis as well as in other diverse autoimmune diseases.
British Journal of Dermatology 03/2011; 164(3):660-4. · 3.67 Impact Factor
-
British Journal of Dermatology 10/2010; 163(4):885-6. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This review summarizes the clinical importance of 18 systematic reviews and guidelines on psoriasis published or indexed between November 2008 and October 2009. The topics covered include guidance on the use of topical, systemic and biological therapies for the treatment of psoriasis; comorbidities associated with psoriasis; and complementary therapies for psoriasis. A similar and more detailed review to this appeared in the 2009 Annual Evidence Update on Psoriasis from NHS Evidence - Skin Disorders in November 2009.
Clinical and Experimental Dermatology 10/2010; 35(7):688-91; quiz 692. · 1.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: There are few reports of the practical use of adalimumab outside of a clinical trial setting and, to our knowledge, none from the U.K.
We assessed the efficacy and safety of adalimumab in a cohort of patients with severe psoriasis attending a tertiary dermatology referral centre in the U.K.
A retrospective case-note review was used to identify all patients initiated on adalimumab for psoriasis. RESI;TS: Baseline Psoriasis Area and Severity Index (PASI) was 24+/-11 (range 9-54; n=46). After 4 months' treatment with adalimumab 64% (29/45), of patients had achieved PASI 75 (75% decrease from baseline) whilst 80% (36/45) of patients met NICE criteria for continuation of treatment. Therapy was well-tolerated. Importantly, 68% (21/31) of patients who had previously received another tumour necrosis factor alpha inhibitor met NICE criteria for continuation of treatment at 16 weeks.
In a cohort of U.K. patients with severe psoriasis, adalimumab has proved to be a significant addition to the expanding armamentarium of biologics for psoriasis. Pharmacovigilance, in the form of registries, is essential to assess the long-term safety of such drugs.
British Journal of Dermatology 10/2010; 163(4):859-62. · 3.67 Impact Factor
-
British Journal of Dermatology 05/2010; 163(4):885 - 886. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The future management of psoriasis will depend on a number of distinct but ultimately inter-related strands of evidence, these are: (i) the interplay of genes and environment and the characterisation of psoriasis phenotypes; (ii) the role of pharmacogenetics in personalised healthcare; (iii) the translation of basic scientific discovery of relevant immune and angiogenic pathways into targeted biologic and small molecule therapies; and (iv) the recognition that the management of any chronic disease is enhanced by an understanding of psychosocial issues. A reductionist approach to development of new therapies will be paramount but serendipity and the prepared mind will contribute, as they have always done.
Actas Dermo-Sifiliográficas 12/2009; 100 Suppl 2:28-31.
-
[show abstract]
[hide abstract]
ABSTRACT: This review summarizes the clinical importance of six systematic reviews on psoriasis published between January 2007 and October 2008. A meta-analysis demonstrated that several traditional nonbiological systemic therapies have equal or superior efficacy to some biological therapies used in the treatment of psoriasis. Two further meta-analyses comparing biological therapies for psoriasis (excluding adalimumab) have established a hierarchy of efficacy for short-term treatment (10-16 weeks): infliximab > etanercept 50 mg twice weekly > etanercept 25 mg twice weekly > efalizumab > alefacept. Excluding adalimumab, rates of adverse events are significantly higher for biological therapies than for placebo, except for etanercept at both 25 and 50 mg twice weekly. Further, head to head trials of biological therapies for psoriasis and longer-term safety data on their use are required. Psoriasis can be induced by and/or exacerbated during antitumour necrosis factor (TNF) therapy. It is recommended to initially switch anti-TNF agent in this situation and only discontinue therapy if psoriasis is extensive and/or intolerable, allowing the primary disease to remain under control. Most screening and monitoring tests carried out during treatment of psoriasis with biological therapies are neither supported nor refuted by current evidence and the clinician must assess each case individually. Studies designed specifically to assess appropriate use of these tests are required. Further research is needed to evaluate the effectiveness of existing psychological interventions in psoriasis. The effectiveness of support groups has not been adequately proven, although there are limited data supporting the use of cognitive behavioural therapy.
Clinical and Experimental Dermatology 07/2009; 34(6):664-7. · 1.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Background The use of methotrexate is limited by interindividual variability in response. Previous studies in patients with either rheumatoid arthritis or psoriasis suggest that genetic variation across the methotrexate metabolic pathway might enable prediction of both efficacy and toxicity of the drug.Objectives To assess if single nucleotide polymorphisms (SNPs) across four genes that are relevant to methotrexate metabolism [folypolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH), methylenetetrahydrofolate reductase (MTHFR) and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC)] are related to treatment outcomes in patients with psoriasis.Methods DNA was collected from 374 patients with psoriasis who had been treated with methotrexate. Data were available on individual outcomes to therapy, namely efficacy and toxicity. Haplotype-tagging SNPs (r2 > 0·8) for the four genes with a minor allele frequency of > 5% were selected from the HAPMAP phase II data. Genotyping was undertaken using the MassARRAY spectrometric method (Sequenom®).Results There were no significant associations detected between clinical outcomes in patients with psoriasis treated with methotrexate and SNPs in the four genes investigated.Conclusions Genetic variation in four key genes relevant to the intracellular metabolism of methotrexate does not appear to predict response to methotrexate therapy in patients with psoriasis.
British Journal of Dermatology 01/2009; 160(2):438 - 441. · 3.67 Impact Factor
-
Clinical and Experimental Dermatology 01/2009; 34(3):415-6. · 1.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The use of methotrexate is limited by interindividual variability in response. Previous studies in patients with either rheumatoid arthritis or psoriasis suggest that genetic variation across the methotrexate metabolic pathway might enable prediction of both efficacy and toxicity of the drug.
To assess if single nucleotide polymorphisms (SNPs) across four genes that are relevant to methotrexate metabolism [folypolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH), methylenetetrahydrofolate reductase (MTHFR) and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC)] are related to treatment outcomes in patients with psoriasis.
DNA was collected from 374 patients with psoriasis who had been treated with methotrexate. Data were available on individual outcomes to therapy, namely efficacy and toxicity. Haplotype-tagging SNPs (r(2) > 0.8) for the four genes with a minor allele frequency of > 5% were selected from the HAPMAP phase II data. Genotyping was undertaken using the MassARRAY spectrometric method (Sequenom).
There were no significant associations detected between clinical outcomes in patients with psoriasis treated with methotrexate and SNPs in the four genes investigated.
Genetic variation in four key genes relevant to the intracellular metabolism of methotrexate does not appear to predict response to methotrexate therapy in patients with psoriasis.
British Journal of Dermatology 10/2008; 160(2):438-41. · 3.67 Impact Factor
