Time and predictors of response to tumour necrosis factor-alpha blockers in psoriatic arthritis: an analysis of a longitudinal observational cohort.

OBJECTIVE: To determine predictors and time to response to treatment with TNF-alpha blockers in patients with PsA in a longitudinal observational cohort. METHODS: We performed a cohort analysis of patients who were followed prospectively in a large PsA clinic. Response to treatment was defined as an improvement of at least 40% in active (tender and/or swollen) and swollen joint count (SJC) and 50% improvement in the Psoriasis Area and Severity Index (PASI) score. RESULTS: Ninety-five patients were included in the analysis. Of the total patients, 72.6 and 77.9% demonstrated 40% improvement in active joint counts at 3 and 12 months, respectively. Also, 80.5 and 87.4% of the patients showed 40% improvement in SJC at 3 and 12 months, respectively. A PASI50 was achieved by 54 and 60.4% after 3 and 12 months of treatment, respectively. Of 17 patients who did not achieve 40% improvement in total SJC at 3 months, 11 (64.7%) responded at 12 months. In multivariate analysis, the number of swollen joints at baseline predicted response of total active joints at 12 months [odds ratio (OR) 1.34; P = 0.02], whereas past use of TNF-alpha blocker decreased odds of response (OR 0.05; P = 0.01). CONCLUSION: TNF-alpha blockers are effective in most PsA patients with the majority responding within 3 months of treatment. A significant proportion of the early non-responders will have a delayed response to treatment. Higher SJC at baseline and no prior use of TNF-alpha blockers predict response.

Axial psoriatic arthritis: update on a longterm prospective study.

OBJECTIVE: To evaluate changes in symptoms, spinal mobility, and radiographic features in patients with axial psoriatic arthritis (AxPsA). METHODS: Patients with AxPsA were identified from the University of Toronto Psoriatic Arthritis clinic database. Axial symptoms, metrology, and radiographic features at study entry were compared to 5-year and 10-year followup assessments. Data were analyzed using continuity adjusted McNemar's test, an exact binomial test, or logistic regression. RESULTS: Of 297 patients (mean age 42.5 yrs, PsA duration 8 yrs) in the study, 56% had axial symptoms, 43% had radiographic evidence of sacroiliitis, and 13% had syndesmophytes at entry. The number of patients with neck/back pain, neck/back stiffness, and clinical sacroiliitis declined significantly at both 5- and 10-year followup periods. There was a significant increase in the number of patients with restricted cervical spinal mobility at both 5- and 10-year visits and significant reduction in lateral flexion at both timepoints. At 5 (10) years, of those without sacroiliitis at baseline, 36.6% (51.7%) developed at least grade 2 sacroiliitis; 46.5% (52.0%) of those who presented with grade 2 progressed to a higher grade; and 15.6% (25.0%) with grade 3 progressed to grade 4 sacroiliitis. Of the patients without cervical/thoracic/lumbar syndesmophytes at study entry, 11%/16%/14% (14%/21%/20%) developed syndesmophytes in these regions at 5 (10) year followup. Similar results were obtained when analyses were restricted to patients satisfying radiographic criteria alone. CONCLUSION: Over a 10-year period, patients with AxPsA had improvement in neck and back pain, but lateral spinal flexion and cervical mobility deteriorated.

Reappraisal of the effectiveness of methotrexate in psoriatic arthritis: results from a longitudinal observational cohort.

OBJECTIVE: In a previous study in our clinic, methotrexate (MTX) conferred no advantage with respect to clinical response or progression of damage after 24 months in patients with psoriatic arthritis (PsA). Our aim was to determine if MTX is being used earlier in the course of PsA and in a higher dose and whether that has led to improved outcomes. METHODS: All patients treated with MTX for at least 24 months in our clinic, between 1994 and 2004, were included in the study. The outcome measures were the progression of radiographic peripheral joint damage score and a > or = 40% reduction in the number of actively inflamed joints. The data from our study were compared to those obtained from our previous study. RESULTS: Fifty-nine patients (36 men) treated with MTX for 24 months were identified. The mean age was 46 years, PsA duration 8 years, and active joint count 12.1 (4.6 swollen). The mean increase in radiographic damage score was 1.5. Sixty-eight percent of patients demonstrated improvement at 24 months. When compared to our previous study, there was a trend for MTX to be used earlier, at a higher dose, with greater clinical improvement and less progression of damage. CONCLUSION: Our study suggests that treatment with MTX has changed in the past decade to include patients with shorter disease duration and less damage, at increased dose, and that there may be better response with less progression of damage.

Relationship between spinal mobility and radiographic damage in ankylosing spondylitis and psoriatic spondylitis: a comparative analysis.

OBJECTIVE: To correlate measures of spinal mobility used in the assessment of spondyloarthritis with radiographic severity, and to compare ankylosing spondylitis (AS) and psoriatic spondylitis (Ps-Sp) in this clinical-radiographic correlation. METHODS: As part of the International SPondyloarthritis Interobserver Reliability Exercise (INSPIRE) study, 20 spondyloarthropathy (SpA) experts met for an examination exercise assessing 19 patients with SpA -- 10 with Ps-Sp (9 men, mean age 52 yrs, mean disease duration 17 yrs) and 9 with AS (7 men, mean age 38 yrs, mean disease duration 16 yrs). Spearman correlation with bias correction was used to correlate median values of the spinal measurements obtained in the INSPIRE study with modified Stoke AS spinal score (mSASSS) and Bath AS Radiology Index-spine (BASRI-s) scores calculated by consensus of 2 assessors. RESULTS: The 2 radiographic measures performed comparably in relation to clinimetrics in the SpA group as a whole. There was very good correlation between mSASSS and the occiput-to-wall distance, tragus-to-wall distance, modified Schober, and lateral spinal flexion in the entire group (rs > 0.64, p < 0.05 for each measure). There was also good correlation between mSASSS and cervical rotation and chest expansion (rs = 0.58 and 0.54, p <0.05, respectively). The clinical-radiographic correlations were comparable in the AS and Ps-Sp, except for cervical rotation, which correlated better with mSASSS in Ps-Sp than in AS. CONCLUSION: Our study documents the structure-function correlations in axial SpA and provides evidence supporting application of radiographic and clinical measures used in AS to studies of Ps-Sp.

Improved survival in psoriatic arthritis with calendar time.

OBJECTIVE: To determine whether there has been a change in mortality rates over the last 3 decades in patients with psoriatic arthritis (PsA) whose cases were followed prospectively. METHODS: Patients receiving followup care according to a standard protocol at the University of Toronto PsA Clinic between 1978 and 2004 were included. Information on patient deaths was collected prospectively. Mortality data for the general population of Ontario, Canada, stratified by 5-year age bands, sex, and calendar year from 1978 to 2004, were used to calculate the reference rates. Standardized mortality ratios (SMRs) were calculated through use of Poisson regression models for the number of observed deaths. Time trend analyses were performed through the use of 10-year "rolling-average" SMRs and followup period-specific SMRs stratified by the period of entry into clinic. RESULTS: Of 680 patients with PsA, 106 (15.6%) (55 women and 51 men) have died. Major causes of death were disease of the circulatory system, neoplasms, diseases of the respiratory system, diseases of the gastrointestinal system, injuries/poisoning, and unknown. The overall SMR for the period 1978-2004 was 1.36 (95% confidence interval 1.12, 1.64). The estimated number of life-years lost by the PsA patient cohort overall was 2.99 years (95% confidence interval 1.14, 4.77). For patients who entered the cohort during the years 1978-1986, the SMRs were 1.89, 1.83, and 1.21 for followup periods 1978-1986, 1987-1995, and 1996-2004, respectively. For patients who entered the cohort during the years 1987-1995, the SMRs were 0.55 and 0.82, while the SMR for those who entered during 1996-2004 was 0.56. CONCLUSION: The drop in SMRs in this PsA clinic population suggests that the mortality risk has improved over time. This improved survival may reflect disease severity at presentation in the earlier cohort as well as earlier diagnosis and more aggressive treatment in the more recent followup period.

A longitudinal study of the effect of disease activity and clinical damage on physical function over the course of psoriatic arthritis: Does the effect change over time?

OBJECTIVE: To investigate whether there are differential effects of disease activity and damage on physical functioning as measured by the Health Assessment Questionnaire (HAQ) over the course of psoriatic arthritis (PsA). METHODS: Between June 1993 and March 2005, 382 patients attending the University of Toronto PsA clinic had completed > or =2 HAQs on an annual basis. At the time of each HAQ assessment, clinical and laboratory measures of disease activity and damage were recorded. Generalized linear mixed-effects models were used to investigate the longitudinal relationship between disease activity, damage, and the HAQ score. To avoid floor effects that would arise in a single mixed-effects model, we adopted a 2-part model. RESULTS: The number of actively inflamed joints (measure of disease activity) and the number of clinically deformed joints (measure of damage) were positively and significantly related to the HAQ score. Furthermore, interaction terms for illness duration with the number of actively inflamed joints were statistically significant, with or without inclusion of the erythrocyte sedimentation rate and morning stiffness in the model (P = 0.029 and P < 0.001, respectively). The positive effects of actively inflamed joints on the level of the HAQ score decreased over increasing duration of PsA. There was less evidence to suggest that the positive effect of joint damage on the HAQ score increased over time. CONCLUSION: Our results support the view that the influence of disease activity on HAQ scores declines with increased disease duration. We could not demonstrate strong evidence that the effect of clinical damage increases over the course of illness.

Predictors for radiological damage in psoriatic arthritis: results from a single centre.

BACKGROUND: The predictors for the development of clinical damage in psoriatic arthritis (PsA) have been reported previously. AIM: To identify predictors for radiological damage in PsA. METHODS: Patients followed-up prospectively according to a standard protocol at The University of Toronto between 1978 and 2004 were included. The principal outcome was the change in the number of damaged joints between visits, both clinically and radiologically. Explanatory variables considered included: sex, age, duration of arthritis at first visit, time in clinic, number of tender swollen joints, functional class, erythrocyte sedimentation rate (ESR), concentration of drugs and, to adjust for within-patient correlation, the number of clinically damaged joints at the first of the two visits over which change was observed. RESULTS: At the time of this analysis, 625 patients were recorded in the database. Multivariate analyses of predictors for both clinical and radiological damage show that age, time in clinic, initial ESR, number of tender and swollen joints at previous visit, and number of deformed joints at previous visit were related to both clinical and radiological damage. CONCLUSIONS: The number of actively inflamed joints, particularly the number of swollen joints, was associated with the progression of radiological damage. The higher the number of previously damaged joints, the higher the risk for progression of damage. Thus, patients with PsA need to be treated, even in the presence of damage as long as there is evidence of inflammation, to prevent the progression of damage.

Quality of life and functional status in systemic sclerosis compared to other rheumatic diseases.

OBJECTIVE: To assess clinical factors associated with disability and physical health in patients with systemic sclerosis (SSc) compared to psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) and healthy controls. METHODS: Eighty-two patients with SSc, 82 with PsA, 74 with SLE, 42 with RA, and 60 controls were recruited from various rheumatology clinics and underwent physical examination, tender point count, Health Assessment Questionnaire Disability Index (HAQ-DI) and Short Form-36 Health Survey (SF-36) assessments. RESULTS: SSc patients were younger and had shorter disease duration than the comparator groups. SSc patients with joint involvement had significantly poorer HAQ-DI scores than patients with PsA (1.43 vs 0.84; p < 0.05), and had higher visual analog scale pain scores than RA patients (1.37 vs 1.01; p < 0.05). The SF-36 Physical Component Summary and HAQ-DI score in SSc patients were adversely affected by joint involvement (p < 0.01, p < 0.001, respectively), >or= 11 tender points (p < 0.01, p < 0.001), gastrointestinal (GI) involvement (p < 0.01, p < 0.01), and high skin score (p = 0.02, p < 0.001). CONCLUSION: Physical health relating to quality of life is adversely affected in patients with SSc. Disability is associated with the presence of >or= 11 tender points, a high skin score, and joint and GI involvement. Joint involvement in SSc is more disabling than joint involvement in PsA; and patients with SSc experience more severe pain than patients with RA.

Reporting of mortality in a psoriatic arthritis clinic is primarily a function of the number of clinic contacts and not disease severity.

OBJECTIVE: To identify processes that influence data collection, particularly in the reporting of deaths in mortality studies, using patient registry data. METHODS: The University of Toronto Psoriatic Arthritis Clinic has mechanisms for patient followup and identification of deaths. Logistic regression was used to identify patient characteristics that discriminate between 2 populations of deaths, those reported under regular followup and those reported in the context of special studies. Factors examined were based on information available at the patients' last clinic visit and the pattern of patients' clinic visits. RESULTS: A clear relationship was found between the number of contacts with the clinic and rapid death reporting. However, no particular link between severity of disease and the reporting of death was apparent in this study. CONCLUSION: It is recommended that research databases routinely record the time between death and reporting of death and the method of ascertaining and reporting death. More detailed information on the scheduling of clinic visits may also be helpful.

Description and prediction of physical functional disability in psoriatic arthritis: a longitudinal analysis using a Markov model approach.

OBJECTIVE: To describe the longitudinal course of physical functioning in patients with psoriatic arthritis. METHODS: Between June 1993 and June 2003, 341 patients attending the University of Toronto Psoriatic Arthritis Clinic completed 2 or more Health Assessment Questionnaires (HAQs). At the time of administration of each HAQ, patients were assigned to 1 of 3 physical functional disability states, based on their HAQ score. A Markov model that allowed for transitions to and from these 3 disability states was used to characterize the longitudinal course of physical functioning, as well as to identify factors for both progression and regression of disability. RESULTS: Despite patient variability in the course of physical functioning, the following 3 longitudinal patterns were observed: 1) a stable state of disability throughout the entire study period, with 28%, 12%, and 6% of patients experiencing no, moderate, or severe disability, respectively; 2) a steady improvement or deterioration in disability over time (this pattern was observed in 27% of patients); and 3) a fluctuating state of disability, occurring in 27% of the patients. Sex, age, disease duration, number of actively inflamed joints, and number of deformed joints predicted transitions between disability states. CONCLUSION: Although 28% of patients appeared resistant to becoming disabled over the duration of this study, the remaining patients were observed either to experience enduring disability or to move between disability states.