Charlotte Cavill

Smoking and delay to diagnosis are associated with poorer functional outcome in psoriatic arthritis

Objective To identify predictors of poorer physical function in established psoriatic arthritis (PsA). Methods PsA patients with disease duration of ≥10 years were identified from the Bath longitudinal cohort. Physical function was assessed using the Stanford Health Assessment Questionnaire (HAQ). Sex, age at diagnosis, duration of symptoms prior to diagnosis, smoking, treatment and year of diagnosis were included in a multivariable regression analysis to identify associations with HAQ. Results 267 patients were identified for inclusion. The median age was 56 years (IQR 45–63), median disease duration was 13 years (IQR 10–18) and median HAQ score was 0.63 (IQR 0.13–1.25). The model predicted significant increases in HAQ related to smoking (0.23, 95% CI 0.04 to 0.42), age >50 years at diagnosis (0.27, 95% CI 0.03 to 0.51), symptom duration of ≥1 year before diagnosis (0.22, 95% CI 0.02 to 0.42), female sex (0.39, 95% CI 0.20 to 0.57) and history of treatment with an anti-TNF agent (0.63, 95% CI 0.32 to 0.93) at follow-up. Conclusions Smoking, delay to diagnosis, older age at diagnosis, female sex and a history of anti-TNF treatment are associated with worse physical function in established PsA.

The ClASsification for Psoriatic ARthritis (CASPAR) Criteria – A Retrospective Feasibility, Sensitivity, and Specificity Study

Objective. To evaluate the sensitivity, specificity, and feasibility of the ClASsification criteria for Psoriatic ARthritis (CASPAR) to retrospectively classify an existing research cohort. Methods. In total, 480 patient records were reviewed from the Royal National Hospital for Rheumatic Diseases Psoriatic Arthritis (PsA) cohort and for 100 consecutive controls with inflammatory arthritis from a general rheumatology clinic. The CASPAR score was modified for retrospective use; both “inflammation” and “current psoriasis” were recorded as present if they had ever been confirmed in the rheumatology clinic. Sensitivity and specificity of the CASPAR criteria were compared with expert clinical diagnosis. Results. A total of 480 database records were identified. Nine sets of records had been lost or destroyed. The diagnoses had changed in 15 cases, which were transferred to the control arm, leaving 456 patients with an expert diagnosis of PsA. Of 115 controls, 96 had rheumatoid arthritis, 5 osteoarthritis, 3 reactive arthritis, 3 seronegative arthritis, 3 undifferentiated arthralgia, 2 ankylosing spondylitis, 1 spondyloarthritis, and 2 systemic sclerosis. Sensitivity (99.7%) and specificity (99.1%) were both high and equivalent to previous reports. Sensitivity remained high even after inclusion of 7 PsA patients with insufficient data to complete the CASPAR assessment (sensitivity 98.2%, specificity 99.1%). The criteria were found to be easy and practical to apply to case records. Conclusion. Our study demonstrates that the feasibility, specificity, and sensitivity of the CASPAR are maintained when adapted for retrospective use to classify an established research cohort.

Mortality in Psoriatic Arthritis – A Single-center Study from the UK

Objective. To determine whether the mortality in a cohort of patients with psoriatic arthritis (PsA) from a single center in the UK is significantly different from the general UK population. Methods. Patients who were entered onto the PsA database at the Royal National Hospital for Rheumatic Diseases, Bath, between 1985 and 2007 were included in this study. Information on patient deaths was collected retrospectively. The National Health Service (NHS) Strategic Tracing Service was used to establish which patients were alive and which had died. Date and cause of death were confirmed by death certificates from the Registry of Births, Marriages and Deaths. A standardized mortality ratio (SMR) was calculated by matching the patient data to single-year, 5-year age-banded England and Wales data from the Office of National Statistics. Results. In this cohort of 453 patients with PsA (232 men, 221 women), there were 37 deaths. Sixteen men and 21 women died. The SMR for the men was 67.87% (95% CI 38.79, 110.22), and for the women, 97.01% (95% CI 60.05, 148.92) and the overall SMR for the PsA cohort was 81.82% (95% CI 57.61, 112.78). The leading causes of death in this cohort were cardiovascular disease (38%), diseases of the respiratory system (27%), and malignancy (14%). Conclusion. These results suggest that mortality in our single-center PsA cohort is not significantly different from the general UK population. No increased risk of death was observed in this cohort.

Exploring ankylosing spondylitis-associated ERAP1, IL23R and IL12B gene polymorphisms in subphenotypes of psoriatic arthritis

OBJECTIVE To ascertain whether AS-associated polymorphisms of ERAP1, IL23R and IL12B genes associate with subphenotypes of PsA, particularly axial radiographic disease once stratified by HLA-B27 and HLA-Cw*0602 status. METHODS rs30187 (ERAP1 gene), rs6887695 (IL12B gene), rs11209026 and rs7530511 (IL23R gene) single nucleotide polymorphisms were genotyped in 263 PsA cases from a prospective cohort and compared with data from healthy controls (n = 3266-5422). ERAP1 results were stratified according to HLA-B27 and HLA-Cw*0602 status. Investigation of association with age at onset of psoriasis/PsA, arthritic joint count, axial radiographic disease, peripheral radiographic erosions, Psoriasis Area Severity Index, nail score and HAQ was made. RESULTS There was a strong association between rs6887595 (IL12B) and PsA, with homozygosity for the major allele being more frequent in PsA than controls (odds ratio 1.70; 95% CI 1.3, 2.2; P < 0.001). A trend was demonstrated for the minor allele of rs11209026 (IL23R) to be less frequent in patients with erosive joint disease than in those without erosions or controls (7%, 14% and 12%, respectively). None of the polymorphisms associated with the presence of axial radiographic disease or other clinical parameters. CONCLUSION We have confirmed a strong association between rs6887595 (IL12B) and PsA. A trend has been demonstrated between an IL23R variant and peripheral erosive disease. ERAP1 was not associated with axial radiographic disease in PsA. Spinal involvement in PsA may be genetically different from that in AS, which is in keeping with previous observations that the clinical and radiographic pattern of axial disease also differs.

A modified sharp score demonstrates disease progression in established psoriatic arthritis

To use a modified Sharp score (MSS) to measure radiologic progression and to assess its relationship to other radiologic features, peripheral joint disease, and physical function in psoriatic arthritis (PsA).

Psoriatic Arthritis Mutilans: Characteristics and Natural Radiographic History

Objective. (1) To compare clinical characteristics of patients with psoriatic arthritis (PsA) with PsA mutilans (PAM) and without PAM, and (2) to determine the rate of PAM radiographic progression. Methods. A retrospective cohort study was conducted of all patients with PsA attending a teaching hospital. The most recent hand and feet radiographs were screened for PAM. Serial radiographs (earliest to most recent) were quantitatively scored for osteolysis, erosion, joint space narrowing, and osteoproliferation. Results. Out of the 610 cases, 36 PsA cases had PAM (5.9%). PAM cases were younger at diagnosis of PsA than non-PAM cases (p = 0.04), had more prevalent psoriatic nail dystrophy (OR 5.43, p < 0.001), and worse health assessment questionnaire score (1.25 vs 0.63, p < 0.04). Radiographic axial disease (OR 2.31, adjusted p = 0.03) and especially radiographic sacroiliitis (OR 2.99, adjusted p = 0.01) were more prevalent in PAM. PAM were more likely than non-PAM cases to have used a disease-modifying antirheumatic drug (DMARD; OR 16.36, p < 0.001). Out of 33 cases, 29 PAM cases had initiated a synthetic DMARD and 4/13 had initiated anti-tumor necrosis factor (anti-TNF) prior to first demonstration of PAM. A median 5 radiographs were scored for each PAM case (interquartile range 3–7). PAM progressed from monoarticular (60%) to polyarticular (80%) involvement. Osteolysis was initially rapid and progressive in the hands and feet, tapering later during disease course. Nail dystrophy predicted more severe osteolysis (p = 0.03). Conclusion. Compared with non-PAM cases, PAM cases have earlier age at PsA diagnosis, poorer function, more prevalent nail dystrophy, and more radiographic axial disease/sacroiliitis. The rate of osteolysis is higher in earlier disease, and more severe in those with nail dystrophy. DMARD and anti-TNF therapy appear not to prevent PAM occurrence.

Validation of the Psoriatic Arthritis Impact of Disease (PsAID) Questionnaire and its potential as a single-item outcome measure in clinical practice

Objectives The Psoriatic Arthritis Impact of Disease (PsAID) Questionnaire is a recently developed patient-reported outcome measure (PROM) of disease impact in psoriatic arthritis (PsA). We set out to assess the validity in an independent cohort of patients, estimate the minimally important difference for improvement and explore the potential of individual components of the PsAID in clinical practice. Methods Data were collected prospectively for a single-centre cohort of patients with PsA. Construct validity was assessed by Spearman correlation with other PROMs and reliability by intraclass correlation coefficient (ICC) at 1 week. Sensitivity to change at 3 months was determined by the standardised response mean (SRM) in those patients with active disease requiring a change in treatment. Results A total of 129 patients (mean ±SD age 52.1±13.3, 57% women, disease duration 10.2±8 years) completed the baseline questionnaires and assessments. The mean baseline PsAID12 score was 3.92±2.26 with an ICC of 0.91 (95%CI 0.87 to 0.94). The SE of measurement was 0.51 and the minimal detectable change was 1.41. There was strong correlation (r≥0.70) with most of the PROMs studied and moderate correlation with clinical outcomes (r=0.40–0.57). The SRM of the PsAID12 was 0.74 (95%CI 0.45 to 0.97). There was strong correlation with individual PsAID items and their corresponding PROM questionnaires (r≥0.67). Conclusion The PsAID is a reliable, feasible and discriminative measure in patients with PsA. The good responsiveness of the PsAID and strong correlation of individual items with other PROMS represent an opportunity to reduce questionnaire burden for patients in studies and clinical practice.

Tumour necrosis factor inhibitor survival and predictors of response in axial spondyloarthritis—findings from a United Kingdom cohort

Objectives To analyse long-term survival and efficacy of TNFi, reasons for switching or discontinuing, baseline predictors of response and remission in axial spondyloarthritis (axSpA) patients in a UK cohort. Methods All patients with a physician-verified diagnosis of axSpA attending two specialist centres who fulfilled the eligibility criteria for TNFi were included. Routinely recorded patient data were reviewed retrospectively. Initial TNFi was recorded as the index drug. Results Six hundred and fifty-one patients (94% AS) were included; adalimumab (n = 332), etanercept (n = 205), infliximab (n = 51), golimumab (n = 40) and certolizumab pegol (n = 23) were index TNFi. The mean (s.d.) duration from symptom onset to time of diagnosis was 8.6 (8.7) years and mean (s.d.) duration from diagnosis to TNFi initiation was 12.6 (11.5) years. A total of 224 (34.4%) stopped index TNFi, and 105/224 switched to a second TNFi. Median drug survival for index and second TNFi were 10.2 years (95% CI: 8.8, 11.6 years) and 5.5 years (95% CI: 2.7, 8.3 years), respectively (P < 0.05). Survival rates were not influenced by choice of TNFi. HLA-B27 predicted BASDAI50 and/or two or more point reduction within 6 months and long-term drug survival (P < 0.05). Low disease activity was predicted by non-smoking and low baseline BASDAI (P < 0.05). Conclusion We have observed good TNFi survival rates in axSpA patients treated in a real-life setting. This is best for first TNFi and not influenced by drug choice.

Comment on: Tumour necrosis factor inhibitor survival and predictors of response in axial spondyloarthritis — findings from a United Kingdom cohort: Reply

SIR, We read with interest the report by Yahya et al. [1] on tumour necrosis factor inhibitor (TNFi) survival and predictors of response in axial spondyloarthritis (axSpA) patients treated in a real-life setting in the UK, where no sex differences were identified impacting these outcomes. Data over the last decade suggest sex-attributable differences in disease features, clinical outcomes and treatment response in axSpA, with a longer diagnostic delay [2], older age at disease onset [3] and higher number of affected first-degree relatives [4] in females. These findings suggest that a higher genetic load is needed in order to develop the disease in females than in males [5]. Furthermore, women appear to have a higher burden of disease [3], reduced response to TNFi [6, 7] and higher switching rate [8]. Characterization of these differences is essential for a better understanding of the disease trajectory in order to deliver optimal personalized medical management. Here, we report our experience from a single tertiary centre in a large teaching hospital, exploring the role of sex in treatment response, drug survival and switching rate in a cohort of biologic-treated axSpA patients. As part of service development and to comply with mandatory audit according to National Health Service governance systems, we conducted a retrospective evaluation of anonymized data using the Leeds Spondyloarthritis Service database. Subjects were eligible if they had a physician-verified diagnosis of radiographic axSpA fulfilling the modified New York criteria (mNYC) for AS and if they received the first TNFi between 1999 and 2017. Exclusion criteria included being prescribed the first TNFi for a diagnosis other than AS, not having TNFi as the first biological (switch to another biological class was allowed), having a follow-up <12 months or participating in the placebo arm of a clinical trial. In compliance with National Institute for Health and Care Excellence guidance, all subjects had a BASDAI 4 at initiation of the first TNFi. Information on disease characteristics, patient-reported outcomes for disease activity (BASDAI), function (BASFI) and pain (visual analog scale) were available at baseline. Treatment response was evaluated by the improvement of 50% in BASDAI (BASDAI50) after 3–6 months (first evaluation) and 1–1.5 years (second evaluation) of treatment. Kaplan–Meier curves were calculated to describe drug survival, and the log-rank test was used to test for differences between the sexes. Discontinuation was classified as attributable to non-response, intolerance (including adverse events) or other reasons (patient decision, death, finished a trial), and the frequency of switching between biologicals was calculated by sex for each drug. All statistical analyses were done in SPSS software (SPSS Statistics, version 21). Data from 280 patients (75 females and 205 males) were available for analysis (Supplementary Table S1, available at Rheumatology Advances in Practice online). Significant differences between the sexes were observed, with females having a higher prevalence of IBD at the baseline (21.3 vs 9.8%; P1⁄4 0.010) and family history of SpA (61.4 vs 41.8%; P1⁄4 0.013) than males. No other sex differences were observed with regard to age at diagnosis, disease onset, delay in diagnosis, symptom duration, patient-reported outcomes or baseline CRP. At the first evaluation, more females reached BASDAI50, but this was not sustained at the second evaluation (Supplementary Tables S2 and S3, available at Rheumatology Advances in Practice online). In contrast to the findings of Yahya et al. [1], females showed a significantly shorter drug survival for the first drug compared with males (median, 34.4 vs 91.6 months; P < 0.001), but this difference was not significant for the total number of biological drugs (Fig. 1). More females than males discontinued treatment owing to intolerance (Supplementary Figure S1, available at Rheumatology Advances in Practice online), which includes adverse events (81.3 vs 48.6%). A total of 40.4% of patients switched to a second drug, with more females than males (53.3 vs 35.6%) mainly because of non-response. Our cohort comprises solely AS patients, with a switching rate similar to the DANBIO registry [8] but higher than that reported by Yahya et al. [1], probably reflecting locally agreed commissioning pathways. There are a number of limitations to our report, such as the retrospective design, small sample size and missing BASDAI data, which lead to a low statistical power; however, these data provide one of the longest observational reports to date, with some patients being followed up for 19 years. In conclusion, in our cohort there was no difference in disease burden between sexes at the time of TNFi initiation, although females had a higher prevalence of IBD and more relatives with SpA, as shown by other groups. Although no sex difference in treatment response was seen, a higher switching rate and shorter drug survival of the first TNFi was seen in females compared with L E T T E R

Trajectory of radiographic change over a decade: the effect of transition from conventional synthetic disease-modifying antirheumatic drugs to anti-tumour necrosis factor in patients with psoriatic arthritis

Objectives To describe the trajectory of radiographic progression among patients with PsA who transitioned from conventional synthetic DMARDs to anti-TNF-α inhibitors in routine care. Methods A retrospective sample of patients with PsA (ClASsification criteria for Psoriatic ARthritis) was taken from the Bath longitudinal cohort. All patients had radiographs of the hands and feet taken: 5 years before (T0), at the time of (T1) and 5 years after (T2) commencing anti-TNF treatment. Radiographs were scored blinded using the PsA-modified Sharp-van der Heijde score (mSvdHS) and for osteoproliferation (Psoriatic Arthritis Ratingen Score) by A.Allard, A.Antony and W.T. This sample size was calculated to ensure 90% power to determine the smallest detectable difference of the mSvdHS to a 5% significance level. Cumulative probability plots were used to determine the probability of radiographic progression pre- (T0-T1) and post- (T1-T2) anti-TNF treatment. Results Eighty-four radiographs from 28 patients were selected for inclusion. The median [interquartile range (IQR)] disease duration at baseline (T0) was 8.5 (0-19.5) years. The interval between T0-T1 and T1-T2 was 4.2 years (3.34-6.65) and 4.9 years (4.25-5.87), respectively. The median mSvdHS at baseline (T0) was 8.5 (IQR 1.75-27.5). The median (IQR) rate of change in mSvdHS per year reduced after commencing anti-TNF, from 2.1 (0.88-3.92) between T0-T1 to 1.0 (IQR 0.05-2.35) between T1-T2 (P = 0.012). Conclusion The trajectory of damage accumulation over a 10-year period in this observational clinical cohort is low overall. The rate of radiographic damage as measured by the mSvdHS slows following commencement of anti-TNF.