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D D Gladman

Publications and source records attributed to D D Gladman.

At least 19 recordsLinked to original sources
PubMed2006

Infliximab maintains a high degree of clinical response in patients with active psoriatic arthritis through 1 year of treatment: results from the IMPACT 2 trial.

OBJECTIVE: To evaluate the efficacy and safety of infliximab through 1 year in patients with psoriatic arthritis (PsA) enrolled in the IMPACT 2 trial. METHODS: In this double blind, placebo controlled, phase III study, 200 patients with active PsA were randomised to receive infusions of infliximab 5 mg/kg or placebo at weeks 0, 2, 6, and every 8 weeks thereafter through 1 year. Patients with persistent disease activity could enter early escape at week 16, and all remaining placebo patients crossed over to infliximab at week 24. Patients randomised to infliximab who had no response or who lost response could escalate their dose to 10 mg/kg starting at week 38. Clinical efficacy was assessed based on the proportion of patients achieving ACR 20 and PASI 75 responses. Major clinical response (that is, maintenance of ACR 70 response for 24 continuous weeks) was assessed for the first time in PsA. RESULTS: Through 1 year of treatment, 58.9% and 61.4% of patients in the randomised infliximab and placebo/infliximab groups, respectively, achieved ACR 20; corresponding figures for PASI 75 were 50.0% and 60.3%. At week 54, major clinical response was achieved by 12.1% of patients in the infliximab group. The safety profile of infliximab through week 54 was consistent with that seen through week 24. Two malignancies occurred: basal cell skin cancer (placebo) and stage I Hodgkin's lymphoma (infliximab). CONCLUSION: Infliximab maintains a high degree of clinical efficacy and continues to be well tolerated in patients with PsA through 1 year of treatment.

Adult↗
PubMed2006

Adalimumab improves joint-related and skin-related functional impairment in patients with psoriatic arthritis: patient-reported outcomes of the Adalimumab Effectiveness in Psoriatic Arthritis Trial.

OBJECTIVE: To evaluate the effects of adalimumab on patient-reported outcomes of joint-related and skin-related functional impairment, health-related quality of life, fatigue and pain in patients with psoriatic arthritis (PsA). METHODS: Patients with moderately- to severely- active PsA were treated with adalimumab, 40 mg, every other week, or placebo, in this 24-week, randomised, controlled trial. Patient-reported outcomes included the Health Assessment Questionnaire Disability Index (HAQ DI), Short-Form 36 Health Survey (SF-36), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale and the Dermatology Life Quality Index (DLQI). RESULTS: Adalimumab (n = 151) and placebo (n = 162) groups were comparable with respect to baseline demographics and disease severity. Significant changes from baseline in HAQ DI were reported for adalimumab v placebo (-0.4 v -0.1, p<0.001) at both 12 and 24 weeks. At week 24, significant improvements in the SF-36 domains of physical functioning, role-physical, bodily pain, general health, vitality and social functioning, as well as the physical component summary score, were observed for adalimumab versus placebo (p<0.01). These reported changes in HAQ DI and SF-36 were also clinically important. Significantly more patients treated with adalimumab had complete resolution of functional loss (HAQ DI = 0) and dermatological-related functional limitations (DLQI = 0) compared with placebo at weeks 12 and 24 (p< or =0.001). Adalimumab led to significantly greater improvements in FACIT-Fatigue scores, pain scores, and disease activity measures versus placebo at 12 and 24 weeks (p<0.001 for all). CONCLUSIONS: Adalimumab improved physical-related and dermatological-related functional limitations, HRQOL, fatigue and pain in patients with PsA treated for 24 weeks.

Adalimumab↗
PubMed2006

Mortality in systemic lupus erythematosus.

OBJECTIVE: To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. METHODS: Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. RESULTS: The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration <1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. CONCLUSION: Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished.

Adolescent↗
PubMed2006

Modification of hypertension and hypercholesterolaemia in patients with systemic lupus erythematosus: a quality improvement study.

BACKGROUND: Hypercholesterolaemia and hypertension are risk factors for coronary artery disease in patients with systemic lupus erythematosus (SLE). OBJECTIVE: To examine the recognition and management of hypercholesterolaemia and hypertension in patients with SLE before and after a quality improvement study. METHOD: Patients with SLE have been followed up prospectively at the University of Toronto Lupus Clinic since 1970. The charts of all patients who entered the clinic since 1990 were reviewed to ensure completeness of data on anti-hypertensive treatment (AHT) and lipid lowering agents (LLA). Recognition and management of hypercholesterolaemia and hypertension were evaluated for the periods 1990-1995 and 1996-2001. RESULTS: Comparison of treatment between time periods showed that during 1990-1995 204/559 (36%) patients seen were hypertensive, of whom 180 (88%) were receiving AHT, and during 1996-2001 241/576 (42%) patients seen were hypertensive, of whom 232 (96%) were receiving AHT (p = 0.0013). A comparison of treatment for hypercholesterolaemia showed that 21/236 (9%) hypercholesterolaemic patients were being treated with LLA in the earlier period compared with 74/261 (28%) in the later period (p<0.0001). CONCLUSIONS: Treatment for hypertension and hyperlipidaemia has increased in the past 6 years compared with the previous 6 years, but a number of patients eligible for these treatments remain untreated.

Adult↗
PubMed2006

Mortality related to cerebrovascular disease in systemic lupus erythematosus.

The objective of this study was to examine mortality rates related to cerebrovascular disease in systemic lupus erythematosus (SLE) compared to the general population. Our sample was a multisite Canadian SLE cohort (10 centres, n = 2688 patients). Deaths due to cerebrovascular disease were ascertained by vital statistics registry linkage using ICD diagnostic codes. Standardized mortality ratio (SMR, ratio of deaths observed to expected) estimates were calculated. The total SMR for death due to cerebrovascular disease was 2.0 (95% confidence interval [CI] 1.0, 3.7). When considering specific types of events, the category with the greatest increased risk was that of ill-defined cerebrovascular events (SMR 44.9 95% CI 9.3, 131.3) and other cerebrovascular disease (SMR 8.4, 95% CI 2.3, 21.6). Deaths due to cerebral infarctions appeared to be less common than hemorrhages and other types of cerebrovascular events. Our data suggest an increase in mortality related to cerebrovascular disease in SLE patients compared to the general population. The large increase in ill-defined cerebrovascular events may represent cases of cerebral vasculitis or other rare forms of nervous system disease; alternately, it may reflect diagnostic uncertainty regarding the etiology of some clinical presentations in SLE patients. The suggestion that more deaths are attributed to cerebral hemorrhage, as opposed to infarction, indicates that inherent or iatrogenic factors (eg, thrombocytopenia or anticoagulation) may be important. In view of the paucity of large-scale studies of mortality attributed to neuropsychiatric outcomes in SLE, our findings highlight the need for additional research in large SLE cohorts.

Adolescent↗
PubMed2005

Clinical and radiological damage in psoriatic arthritis.

BACKGROUND: Psoriatic arthritis may progress to joint damage. Joint damage may be assessed clinically, by identifying deformed, fused, or flail joints, or radiologically, by recording erosions, joint space narrowing, ankylosis, lysis, or surgery. The relation between clinical and radiological damage is unclear. OBJECTIVE: To study the ordering of clinical and radiological damage detection, and the clinical features associated with the type of damage detected first. METHODS: The University of Toronto psoriatic arthritis database was used to relate clinical and radiological damage in the hand joints in 655 patients followed prospectively between 1978 and 2003. Generalised estimating equations were used to fit logistic regression models to identify factors that predict classification of damage by radiographic assessment first. RESULTS: The majority of the joints were not informative, as they either had evidence of damage by both methods at entry, or remained undamaged. Of the remainder, 81% of the joints showed radiological damage first and 19% had clinical damage first. Development of radiological damage first was related to previous detection of swollen joints, and was inversely related to duration of arthritis. CONCLUSIONS: Radiological damage is often detected before clinical damage is observed. Clinical inflammation often precedes the detection of radiological damage.

Adolescent↗
PubMed2005

Association of SEEK1 and psoriatic arthritis in two distinct Canadian populations.

OBJECTIVE: To examine the relationship between SNP +39604 in SEEK1 and psoriatic arthritis (PsA) in two distinct Canadian populations. METHODS: 103 patients with PsA and 105 ethnically matched controls from Newfoundland and 202 patients with PsA and 100 controls from Ontario were studied. Patients and controls were genotyped for SNP +39604 of SEEK1 by time of flight mass spectrometry, using the Sequenom platform. Genomic DNA was amplified by the Dynal RELI SSO HLA-Cw* typing kit for HLA-C typing. RESULTS: The frequency of the minor SEEK1(T) allele in subjects with PsA and controls was 48.5% and 32.4%, respectively (odds ratio (OR) = 2.0; p = 0.017), in the Newfoundland population and 46.5% and 38.0%, respectively (OR = 1.4; p = 0.16), in the Ontario population. Although SEEK1 is associated with PsA, particularly in the Newfoundland population, multivariate analysis showed that SEEK1 does not seem to be a further susceptibility factor if the HLA-Cw*0602 status is already known. No association was noted between SEEK1(T) allele and onset of psoriasis, PsA, or arthritis pattern. CONCLUSION: SEEK1 is associated with PsA in the Newfoundland founder population. This association is probably due to linkage disequilibrium between SEEK1 and HLA-Cw*0602 in this population.

Adult↗
PubMed2005

Psoriatic arthritis imaging: a review of scoring methods.

Structural damage assessed on conventional radiographs is an important outcome measure in psoriatic arthritis. This article reviews the available scoring methods. A full description of the methods is given as well as information on various aspects of validity.

Arthritis, Psoriatic↗
PubMed2005

Consensus exercise on domains in psoriatic arthritis.

Recent studies with biological therapy in psoriatic arthritis (PsA) have highlighted the need for validated and widely accepted assessment tools and outcome measures for this disease. A Delphi process was established through the CASPAR group where domains for assessment of PsA in clinical trials, longitudinal studies, and rehabilitation were identified. Although the process reduced the list of possible domains to approximately 12, it was not able to detect those that would be most important. Moreover, skin assessment was left out. A further study through the GRAPPA group subsequently identified the following domains: inflammation (peripheral joints, axial skeleton, physician global assessment), other features (dactylitis, enthesitis), skin and nails, imaging, biomarkers, and patient derived indices (pain, quality of life, itch, function), as important in the assessment of patients with PsA. These domains require further refining, and instruments to measure the items need to be developed.

Arthritis, Psoriatic↗
PubMed2005

Psoriatic arthritis clinical registries and genomics.

To understand better a complex disease such as psoriatic arthritis (PsA), collection of a large amount of information on clinical, laboratory, and radiological features is required over an extended period of time. Longitudinal data can be effectively collected and stored in clinical registries and databases. This article reviews current databases in PsA and proposes a structure for an international PsA registry. Careful collection and analysis of patient data through collaborative efforts will likely advance our knowledge of pathogenesis and provide new and much needed insights about the course and prognosis of the disease.

Arthritis, Psoriatic↗
PubMed2005

Autoantibodies in biological agent naive patients with psoriatic arthritis.

BACKGROUND: Anti-tumour necrosis factor alpha (anti-TNFalpha) treatment may be associated with the production of autoantibodies, including lupus-specific autoantibodies. OBJECTIVE: To investigate the prevalence of autoantibodies in biological agent naive patients with psoriatic arthritis (PsA). METHODS: 94 consecutive, prospectively collected, biological agent naive patients with PsA at the University of Toronto PsA clinic underwent clinical and laboratory assessment. Disease activity was assessed by the number of actively inflamed joints, and the Psoriasis Activity and Severity Index (PASI) score. Antinuclear antibodies (ANA), rheumatoid factor (RF), double stranded DNA (dsDNA), Ro, La, Smith, and RNP were tested. Descriptive statistics and non-parametric tests were used to analyse the data. RESULTS: 44/94 (47%) patients with PsA were ANA positive (>/=1/40); 13/94 (14%) had a clinically significant titre of >/=1/80. Three per cent had dsDNA antibodies, 2% had RF and anti-Ro antibodies, 1% had anti-RNP antibodies, and none had anti-La or anti-Smith antibodies. CONCLUSIONS: The background prevalence of ANA >/=1/80 in patients with PsA was 14%, with very few patients having specific lupus antibodies. This should serve as a baseline figure for the frequency of autoantibodies in biological agent naive patients with PsA for studies of the use of anti-TNFalpha agents.

Adult↗
PubMed2005

Psoriatic arthritis: epidemiology, clinical features, course, and outcome.

Psoriatic arthritis (PsA) has been defined as a unique inflammatory arthritis associated with psoriasis. Its exact prevalence is unknown, but estimates vary from 0.3% to 1% of the population. The clinical features described initially are recognised by most experienced clinicians, although they are most distinct in early disease. Initially, PsA typically presents as an oligoarticular and mild disease. However, with time PsA becomes polyarticular, and it is a severe disease in at least 20% of patients. Patients with PsA who present with polyarticular disease are at risk for disease progression. In addition to progression of clinical and radiological damage, health related quality of life is reduced among patients with PsA. It important to note that patients included in recent drug trials resemble patients followed prospectively in a clinic.

Adult↗
PubMed2005

OMERACT 7 psoriatic arthritis workshop: synopsis.

Outcome Measures in Rheumatology (OMERACT) conferences have developed a process by which outcome measures to be included in clinical trials are identified by consensus. During OMERACT 7, held in Asilomar, CA, USA, in May 2004, a workshop on outcome measures in psoriatic arthritis was held. Information derived through a previous Delphi exercise and nominal group process was shared with the participants, as were the results from a study using completed clinical trials with biological therapies. On the basis of the evidence presented and discussions in breakout groups at the OMERACT conference, a set of domains to be included in clinical trials in psoriatic arthritis was developed and a research agenda for further studies in psoriatic arthritis proposed.

Arthritis, Psoriatic↗
PubMed2005

Psoriatic arthritis and imaging.

Psoriatic arthritis (PsA) has historically been considered a milder rheumatic disease not yielding significant clinical damage. However, recent studies have shown that PsA can be deforming and debilitating and that joint damage can be severe. Traditionally, joint damage has been recorded using plain radiographs. Characteristic radiographic features of PsA include joint erosions, joint space narrowing, bony proliferation including periarticular and shaft periostitis, osteolysis including "pencil in cup" deformity and acro-osteolysis, ankylosis, spur formation, and spondylitis. New imaging modalities, including ultrasound, bone scanning, and magnetic resonance imaging may help in both diagnosis and follow up of patients with PsA. These new imaging techniques will with validation help detect early changes in the peripheral joints, the periarticular tissues, and the spinal structures in patients with PsA.

Arthritis, Psoriatic↗
PubMed2005

Psoriatic arthritis assessment tools in clinical trials.

In order to measure disease activity, progression, and change with therapy in psoriatic arthritis (PsA), it is important to use accurate, reliable, and feasible outcome measures that can ideally be employed in longitudinal cohorts, clinical trials, and clinical practice. Until recently, there has been little focus on this methodology in PsA. Clinical trials and long term clinical registries have used disparate outcome measures. With emerging therapies, the focus on the methodology of outcome assessment has increased to ensure that discriminant and responsive instruments are used. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), in conjunction with the society, Outcome Measures in Rheumatology (OMERACT), is focused on refining and developing outcome measures for a variety of disease domains reviewed in this report. Key domains to assess include joints, skin, enthesitis, dactylitis, spine, joint damage as assessed radiologically, quality of life, and function. These domains can be assessed by individual and composite measures. A number of measures have been "borrowed" from the fields of rheumatoid arthritis, ankylosing spondylitis, and psoriasis and adapted to PsA. Others are being developed specifically for PsA. Few are validated but most have been shown to perform well in distinguishing placebo from treatment response. This report reviews the current state of the art of assessment in PsA and points toward future directions of development of this field.

Arthritis, Psoriatic↗