The dynamics of response as measured by multiple composite outcome tools in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) trial

Background: We aimed to evaluate the dynamics of treatment response with different composite measures in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) trial. Methods: Participants with early disease-modifying antirheumatic drug-naïve psoriatic arthritis (PsA) were randomised 1:1 to either tight control (TC; 4 weekly review with therapy escalation if criteria not met) or standard care (SC; 12 weekly review). We calculated modified versions of the Psoriatic ArthritiS Disease Activity Score (PASDAS), Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Composite scorE (GRACE) and Composite Psoriatic Disease Activity Index (CPDAI) at baseline and 12 weekly to 48 weeks by blinded assessor. For missing data, we used the last observation carried forward. Comparison between groups was made by analysis of covariance and comparison of area under the curve (AUC). Results: 206 people were randomised to TC (n=101) or SC (n=105). Significant differences between treatment groups were seen (p<0.0001 for all composite measures). AUC analysis demonstrated a significant difference between groups for the PASDAS but not GRACE and CPDAI. For participants with oligoarthritis, a significant difference between groups was seen for each measure, although the significance levels were greatly diminished (PASDAS, p=0.04; GRACE p=0.01; CPDAI p=0.04). For oligoarthritis using AUC analysis, none of the measures could distinguish between groups. Conclusions: Composite measures of disease activity were able to distinguish between TICOPA treatment arms, although differences were diminished for those with oligoarthritis. Further data are needed to inform the preferred composite measure for use as the primary outcome in PsA trials

The dynamics of response as measured by multiple composite outcome tools in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) trial

Background: We aimed to evaluate the dynamics of treatment response with different composite measures in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) trial. Methods: Participants with early disease-modifying antirheumatic drug-naïve psoriatic arthritis (PsA) were randomised 1:1 to either tight control (TC; 4 weekly review with therapy escalation if criteria not met) or standard care (SC; 12 weekly review). We calculated modified versions of the Psoriatic ArthritiS Disease Activity Score (PASDAS), Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Composite scorE (GRACE) and Composite Psoriatic Disease Activity Index (CPDAI) at baseline and 12 weekly to 48 weeks by blinded assessor. For missing data, we used the last observation carried forward. Comparison between groups was made by analysis of covariance and comparison of area under the curve (AUC). Results: 206 people were randomised to TC (n=101) or SC (n=105). Significant differences between treatment groups were seen (p<0.0001 for all composite measures). AUC analysis demonstrated a significant difference between groups for the PASDAS but not GRACE and CPDAI. For participants with oligoarthritis, a significant difference between groups was seen for each measure, although the significance levels were greatly diminished (PASDAS, p=0.04; GRACE p=0.01; CPDAI p=0.04). For oligoarthritis using AUC analysis, none of the measures could distinguish between groups. Conclusions: Composite measures of disease activity were able to distinguish between TICOPA treatment arms, although differences were diminished for those with oligoarthritis. Further data are needed to inform the preferred composite measure for use as the primary outcome in PsA trials

BSR Spondyloarthritis Course, 27 February 2020. Spondyloarthritis: pathogenesis, diagnosis and management

High-quality continuous medical education is essential to maintain excellence in health-care delivery, upskilling professionals and improving patient outcomes. This is particularly relevant when addressing rare disease groups, such as the spondyloarthritides, a group of heterogeneous inflammatory conditions that affect joints and other organs, such as the skin, bowel and eye. Professional bodies, such as the British Society for Rheumatology (BSR), are well placed to deliver this type of education. In 2020, the BSR ran a dedicated SpA course aimed at rheumatology health-care professionals wishing to update their basic knowledge of SpA with a review of the latest advances in the field. Here, we summarize the proceedings of the meeting and discuss the value of such an initiative

Assessing Disease Activity in Psoriatic Arthritis: A Literature Review

Psoriatic arthritis (PsA) is a multifaceted disease, with a high impact on patients’ psychological and physical well-being. There is increasing recognition that assessment of both clinical aspects of disease and patient identified concerns, such as fatigue, work disability, and treatment satisfaction need to be addressed. Only then can we fully understand disease burden and make well-informed treatment decisions aimed at improving patients’ lives. In recent years, there has been much progress in the development of unidimensional and composite measures of disease activity, as well as questionnaires capturing the patient’s perspective in psoriatic disease. Despite these advances, there remains disagreement amongst clinicians as to which instruments should be used. As a consequence, they are yet to receive widespread implementation in routine clinical practice. This review aims to summarize currently available clinical and patient-derived assessment tools, which will provide clinicians with a practical and informative resource

Disease-specific composite measures for psoriatic arthritis are highly responsive to a Janus kinase inhibitor treatment that targets multiple domains of disease

Background: The multiple disease domains affected in psoriatic arthritis (PsA) may make composite endpoints appropriate for assessing changes in disease activity over time. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Data from two phase 3 studies of patients with PsA were used to evaluate the effect of tofacitinib on composite endpoints. Methods: Oral Psoriatic Arthritis triaL (OPAL) Broaden was a 12-month study of tumor necrosis factor inhibitor (TNFi)-naïve patients with an inadequate response to at least one conventional synthetic disease-modifying anti-rheumatic drug; OPAL Beyond was a 6-month study of patients with inadequate response to TNFi. Patients with active PsA received tofacitinib 5 or 10 mg doses twice daily (BID), adalimumab 40 mg subcutaneous injection once every 2 weeks (OPAL Broaden only), or placebo advancing at month 3 to tofacitinib 5 or 10 mg BID. The disease-specific composites were Psoriatic Arthritis Disease Activity Score (PASDAS), Disease Activity Index for Reactive Arthritis/Psoriatic Arthritis (DAPSA), and Composite Psoriatic Disease Activity Index (CPDAI). Change from baseline in composite endpoints was also assessed for minimal disease activity (MDA) responders versus non-responders. Results: Overall, 422 patients from OPAL Broaden and 394 patients from OPAL Beyond were treated. The mean changes from baseline to month 3 for tofacitinib 5 mg BID, tofacitinib 10 mg BID (standard error; effect size) were OPAL Broaden: PASDAS, −2.0 (0.14; 1.73), −2.4 (0.14; 2.4); DAPSA, −20.2 (1.72; 0.9), −24.4 (1.73; 1.23); and CPDAI, −2.9 (0.34; 1.03), −4.2 (0.36; 1.53); OPAL Beyond: PASDAS, −1.9 (0.14; 1.53), −2.1 (0.14; 1.84); DAPSA, −22.5 (1.67; 0.81), −21.0 (1.70; 0.84); and CPDAI, −3.3 (0.31; 1.41), −3.4 (0.31; 1.45). Greater changes from baseline to month 3 (P ≤0.05) were seen with both doses of tofacitinib versus placebo for all endpoints except CPDAI for tofacitinib 5 mg BID in OPAL Broaden. Effect sizes generally increased from 3 to 6 months. Mean changes from baseline were greater in MDA responders than MDA non-responders for all composite endpoints across all time points and treatments. Conclusions: This analysis suggests that disease-specific composite measures are appropriate for evaluating treatment efficacy on multiple disease domains in PsA. Trial registration: OPAL Broaden: ClinicalTrials.gov Identifier: NCT01877668, first posted June 12, 2013; OPAL Beyond: ClinicalTrials.gov Identifier: NCT01882439, first posted June 20, 2013

The GOLMePsA study protocol: an investigator-initiated, double-blind, parallel-group, randomised, controlled trial of GOLimumab and methotrexate versus methotrexate in early diagnosed psoriatic arthritis using clinical and whole body MRI outcomes

Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis which impacts significantly on the quality of life and work capacity of affected individuals. Recent evidence has shown that early control of inflammation in PsA leads to improved long-term outcomes. It is postulated that prompt intervention after diagnosis using a remission-induction treatment strategy will lead to improved outcomes and optimal disease control of PsA. The aim of the present study was to compare the clinical efficacy of a treatment strategy in newly diagnosed, treatment naïve PsA subjects, using the combination of golimumab (GOL), methotrexate (MTX) and steroids versus standard care (MTX monotherapy plus steroids). Methods/design: GOLMePsA is an investigator initiated, phase IIIb, single-centre, randomised, double-blind, placebo-controlled, two-armed, parallel-group, imaging-supplemented study. Eighty-eight PsA patients, diagnosed within 24 months prior to screening and treatment naïve, will be randomised at baseline to receive: (arm 1) the combination of intramuscular/intra-articular prednisolone, MTX and GOL or (arm 2) the combination of intramuscular/intra-articular prednisolone, MTX and placebo for 24 weeks (interventional period). Primary outcome measure is clinical improvement (at least 1 unit difference) in the Psoriatic ArthritiS Disease Activity Score (PASDAS) composite index. Reflecting a “step down” therapeutic approach, all participants successfully completing the interventional period will be followed up for a further 28 weeks. During this observational period, stable maintenance MTX monotherapy will continue for both arms, unless in case of intolerance or PsA relapse. In the latter case, additional treatment will be provided. Overall, the GOLMePsA study length is planned to be 52 weeks. Discussion: The hypothesis underlining this study is that very early treatment with first-line GOL reduces disease activity in PsA, in comparison to conventional therapy. Trial registration: EudraCT 2013–004122-28. 24/09/2013

Willingness to participate in future HIV prevention studies among gay and bisexual men in Scotland, UK: a challenge for intervention trials

This article examines willingness to participate in future HIV prevention research among gay and bisexual men in Scotland, UK. Anonymous, self-complete questionnaires and Orasure Gäó oral fluid samples were collected in commercial gay venues. 1,320 men were eligible for inclusion. 78.2% reported willingness to participate in future HIV prevention research; 64.6% for an HIV vaccine, 57.4% for a behaviour change study, and 53.0% for a rectal microbicide. In multivariate analysis, for HIV vaccine research, greater age, minority ethnicity, and not providing an oral fluid sample were associated with lower willingness; heterosexual orientation and not providing an oral fluid sample were for microbicides; higher education and greater HIV treatment optimism were for behaviour change. STI testing remained associated with being more willing to participate in microbicide research and frequent gay scene use remained associated with being more willing to participate in behaviour change research. Having an STI in the past 12 months remained significantly associated with being willing to participate in all three study types. There were no associations between sexual risk behaviour and willingness. Although most men expressed willingness to participate in future research, recruitment of high-risk men, who have the potential to benefit most, is likely to be more challenging

The comparative performance of three screening questionnaires for psoriatic arthritis in a primary care surveillance study.

Objectives To compare the performance of three psoriatic arthritis (PsA) screening questionnaires in a primary care psoriasis surveillance study. Methods Participants with psoriasis, and not known to have psoriatic arthritis (PsA), were identified from general practice databases and invited to attend a secondary care centre for a clinical assessment. The three patient-completed screening questionnaires (PEST, CONTEST, and CONTESTjt) were administered along with other patient reported measures and a clinical examination of skin and joints was performed. Participants who demonstrated signs of inflammatory arthritis suggestive of PsA were referred, via their GP, for a further assessment in a secondary care rheumatology clinic. Results A total of 791 participants attended the screening visit and 165 participants were judged to have signs and symptoms of inflammatory arthritis, of which 150 were referred for assessment. Of these 126 were seen and 48 were diagnosed with PsA. The results for each questionnaire were as follows: PEST: Sensitivity 0.625 (95% CI 0.482–0.749), specificity 0.757 (0.724–0.787). CONTEST: Sensitivity 0.604 (0.461–0.731), specificity 0.768 (0.736–0.798). CONTESTjt: Sensitivity 0.542 (0.401–0.676), specificity 0.834 (0.805–0.859). CONTESTjt demonstrated marginally superior specificity to PEST though the area under the ROC curve was similar for all three instruments. Conclusions Minimal differences between the three screening questionnaires were found in this study and no preference can be made based on these results. The choice of which instrument to choose will depend on other factors, such as simplicity and low patient burden

Comparing Psoriatic Arthritis Low-field Magnetic Resonance Imaging, Ultrasound, and Clinical Outcomes: Data from the TICOPA Trial

Objective: The Tight Control of inflammation in Psoriatic arthritis (TICOPA; isrctn.com: ISRCTN30147736) trial compared standard care (StdC) and tight control (TC) in early psoriatic arthritis (PsA), demonstrating better outcomes for TC. This substudy evaluated the performance metrics of modern imaging outcomes and compared them to the clinical data. Methods: Non-contrast 0.2T magnetic resonance imaging (MRI; single hand) was assessed using the Outcomes in Rheumatology (OMERACT) PsA MRI Scoring System (PsAMRIS) with an additional global inflammation score. Ultrasound (US; same hand) was scored for greyscale, power Doppler, and erosions at the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints and scores summated. Results: Seventy-eight patients had paired (baseline and 48 weeks) US data and 61 paired MRI data; 50 had matched clinical, MR, and US data. Significant within-group changes were seen for the inflammatory PsAMRIS components at MCP level: MRI global inflammation [median difference (range), standardized response mean (SRM)]: 3.25 (−5.0 to 12.0), 0.68; 1.0 (−4.5 to 17.5), 0.45 for TC and StdC, respectively. Similar within-group differences were obtained for US: 1.0 (−13.0 to 23.0), 0.45; 3.0 (−6.0 to 21.0), 0.77 for TC and StdC, respectively. No differences were seen between treatment groups. Significant correlations were found between baseline and change MRI and US scores. A significant correlation was found between baseline PsA disease activity scores and MRI global inflammation scores (Spearman ρ for MCP, PIP: 0.46, 0.63, respectively). No differences in erosion progression were observed. Conclusion: The PsAMRIS and US inflammation scores demonstrated good responsiveness. No between-group differences were demonstrated, but this substudy was likely underpowered to determine differences between the 2 treatment strategies

Otitis media in young Aboriginal children from remote communities in Northern and Central Australia: a cross-sectional survey

BACKGROUND: Middle ear disease (otitis media) is common and frequently severe in Australian Aboriginal children. There have not been any recent large-scale surveys using clear definitions and a standardised middle ear assessment. The aim of the study was to determine the prevalence of middle ear disease (otitis media) in a high-risk population of young Aboriginal children from remote communities in Northern and Central Australia. METHODS: 709 Aboriginal children aged 6–30 months living in 29 communities from 4 health regions participated in the study between May and November 2001. Otitis media (OM) and perforation of the tympanic membrane (TM) were diagnosed by tympanometry, pneumatic otoscopy, and video-otoscopy. We used otoscopic criteria (bulging TM or recent perforation) to diagnose acute otitis media. RESULTS: 914 children were eligible to participate in the study and 709 were assessed (78%). Otitis media affected nearly all children (91%, 95%CI 88, 94). Overall prevalence estimates adjusted for clustering by community were: 10% (95%CI 8, 12) for unilateral otitis media with effusion (OME); 31% (95%CI 27, 34) for bilateral OME; 26% (95%CI 23, 30) for acute otitis media without perforation (AOM/woP); 7% (95%CI 4, 9) for AOM with perforation (AOM/wiP); 2% (95%CI 1, 3) for dry perforation; and 15% (95%CI 11, 19) for chronic suppurative otitis media (CSOM). The perforation prevalence ranged from 0–60% between communities and from 19–33% between regions. Perforations of the tympanic membrane affected 40% of children in their first 18 months of life. These were not always persistent. CONCLUSION: Overall, 1 in every 2 children examined had otoscopic signs consistent with suppurative ear disease and 1 in 4 children had a perforated tympanic membrane. Some of the children with intact tympanic membranes had experienced a perforation that healed before the survey. In this high-risk population, high rates of tympanic perforation were associated with high rates of bulging of the tympanic membrane