On Modelling Minimal Disease Activity.

OBJECTIVE: To explore methods for statistical modelling of minimal disease activity (MDA) based on data from intermittent clinic visits. METHODS: The analysis was based on a 2-state model. Comparisons were made between analyses based on "complete case" data from visits at which MDA status was known, and the use of hidden model methodology that incorporated information from visits at which only some MDA defining criteria could be established. Analyses were based on an observational psoriatic arthritis cohort. RESULTS: With data from 856 patients and 7,024 clinic visits, analysis was based on virtually all visits, although only 62.6% provided enough information to determine MDA status. Estimated mean times for an episode of MDA varied from 4.18 years to 3.10 years, with smaller estimates derived from the hidden 2-state model analysis. Over a 10-year period, the estimated expected times spent in MDA episodes of longer than 1 year was 3.90 to 4.22, and the probability of having such an MDA episode was estimated to be 0.85 to 0.91, with longer times and greater probabilities seen with the hidden 2-state model analysis. CONCLUSION: A 2-state model provides a useful framework for the analysis of MDA. Use of data from visits at which MDA status can not be determined provide more precision, and notable differences are seen in estimated quantities related to MDA episodes based on complete case and hidden 2-state model analyses. The possibility of bias, as well as loss of precision, should be recognized when complete case analyses are used

The effectiveness and safety of TNF-alpha blockers in the treatment of early psoriatic arthritis: an Italian multicentre longitudinal observational pilot study

The objective of this study is to assess the effectiveness and safety of TNF-α blockers in a group of early psoriatic arthritis (PsA) patients with an unsatisfactory response to previous conventional treatment consecutively enrolled in five Italian centres. A 24-week open-label trial was carried out in consecutive early PsA patients classified according to the CASPAR criteria, with unsatisfactory response to previous treatments and with a DAS28 threshold as ≥3.2, seen at the outpatient clinics of each centre. Exclusion criteria were previous usage of TNF-α blockers and a disease duration >12 months. The choice of any of the three TNF-α blockers was decided by the expert’s opinion, without any restriction. Effectiveness was considered as an improvement of DAS28 at 12 and 24 weeks of treatment. Secondary endpoints were an improvement of TJC, SWJ, HAQ score and PASI score. Changes from baseline to the 12- and 24-week follow-up assessments were analysed using the Wilcoxon paired sign rank test. Twenty-nine patients (14 males, 15 females, median age 37 years, range 20–65 years) were enrolled. A statistical improvement of the DAS28 was observed at 12 and 24 weeks from baseline (p < 0.001). Secondary endpoints also confirmed the effectiveness of the TNF-α blockers in the treatment of early PsA. No severe adverse events were observed during the treatment period, and no patient withdrew from the medications. This study suggests that the TNF-α blockers can be effective in the management of early PsA. Further controlled studies will provide more data on this challenging topic

An educational leaflet improves response to invitation for screening for arthritis in patients with psoriasis in primary care, but only in practices in the most deprived areas

This study hypothesises that an educational leaflet about psoriatic arthritis (PsA) will improve psoriasis patients’ attendance for screening for PsA. A random sample of patients ≥18 years old with a coded diagnosis of psoriasis and no diagnosis of PsA, rheumatoid arthritis or ankylosing spondylitis were identified from five GP surgeries in Yorkshire, UK. Patients were randomised 1:1 to receive study information alone or with the educational leaflet, with an invitation to attend for a screening examination by a dermatologist and rheumatologist. Nine hundred thirty-two invitation packs were sent to recruit 191 (20.5%) participants. One hundred sixty-nine (88.5%) had current or previous psoriasis and 17 (10.1%) had previously undiagnosed PsA. The estimated prevalence of PsA was 18.1% (95% CI: 16.2, 20.1%). The response rate was lower than expected and was not significantly higher when patients received the educational leaflet (22.8 vs 18.3%, p = 0.08). Response rates varied by practice (14.7 to 30.6%). However, deprivation scores for each practice revealed a significant increase in response with the leaflet for deprivation decile of 3 (p < 0.001) but no significant differences in the other practices. An educational leaflet about PsA improves attendance for screening in primary care, but only in those practices with higher levels of socioeconomic deprivation

Quality of life and satisfaction with life in SLE patients—the importance of clinical manifestations

To assess the correlation between quality of life (QoL) and satisfaction with life (SL) in SLE patients and correlate both with clinical symptoms of the disease. The study was performed in 83 patients. QoL was assessed by Short Form 36, and SL was assessed by the Satisfaction with Life Scale. Clinical manifestations presented at the time of examination were taken into consideration. SLE patients assessed their QoL and SL as rather low. Those with photosensitivity as well as neurological symptoms presented lower QoL in particular domains, while those with renal manifestation of SLE assessed their QoL as higher. Similar observations were made for SL only in relation to neurological symptoms. Moreover, our findings show that although SL is a part of QoL, both these parameters should be distinguished in order to fully assess the state of the patient

Impact of guselkumab, an interleukin-23 p19 subunit inhibitor, on enthesitis and dactylitis in patients with moderate to severe psoriatic arthritis: results from a randomised, placebo-controlled, phase II study

Objective To evaluate the effect of guselkumab on enthesitis and dactylitis in a phase II trial of patients with active psoriatic arthritis (PsA). Methods This was a phase II, randomised, placebo-controlled, double-blind trial of adults with active PsA (≥3 swollen and ≥3 tender joints and C reactive protein ≥0.3 mg/dL) despite conventional synthetic disease-modifying anti-rheumatic drug, non-steroidal anti-inflammatory drug, and/or oral corticosteroid therapy. Patients were randomised to subcutaneous injections of guselkumab 100 mg or placebo at weeks 0, 4 and every 8 weeks, with placebo crossover to guselkumab at week 24. Dactylitis was scored on a scale of 0–3 on each digit; enthesitis was assessed using the Leeds Enthesitis Index (0–6). Other assessments included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index responses. Results Of 149 randomised patients, 107 patients had enthesitis (mean score=2.7) and 81 patients had dactylitis (mean dactylitis score=5.7) at baseline. Mean improvements in enthesitis and dactylitis at week 24 were greater in the guselkumab group versus placebo and sustained through week 56. Similar results were observed for the proportions of patients with resolution of enthesitis and dactylitis. At week 56, mean improvements in enthesitis and dactylitis among patients who switched from placebo to guselkumab treatment were similar to those in the guselkumab group. In the guselkumab group, ACR20 responders had greater improvements in enthesitis and dactylitis versus non-responders (week 24). Conclusions At week 24, the guselkumab group had greater mean improvements in enthesitis and dactylitis and greater proportions of patients with resolution of enthesitis and dactylitis versus placebo. ACR20 response was associated with improvements in enthesitis and dactylitis

Etanercept and Methotrexate as Monotherapy or in Combination for Psoriatic Arthritis: Primary Results From a Randomized, Controlled Phase III Trial

Objective: To examine the efficacy of methotrexate monotherapy relative to etanercept monotherapy and the value of combining methotrexate and etanercept for the treatment of patients with psoriatic arthritis (PsA). Methods: In this double‐blind study, 851 patients with PsA were randomized to 1 of 3 treatment arms, as follows: oral methotrexate (20 mg) plus subcutaneous placebo given weekly (n = 284), subcutaneous etanercept (50 mg) plus oral placebo given weekly (n = 284), or subcutaneous etanercept (50 mg) plus oral methotrexate (20 mg) given weekly (combination therapy; n = 283). The American College of Rheumatology 20% improvement (ACR20) response and Minimal Disease Activity (MDA) response at week 24 were the primary end point and key secondary end point, respectively. Other measures of inflammatory arthritis, radiographic progression, and nonarticular disease manifestations were also assessed. Results: Patients with PsA had a mean ± SD age of 48.4 ± 13.1 years, and the mean ± SD duration of PsA was 3.2 ± 6.3 years (median 0.6 years). ACR20 and MDA response rates at week 24 were significantly greater in patients who received etanercept monotherapy compared with those who received methotrexate monotherapy (ACR20, 60.9% versus 50.7% of patients [P = 0.029]; MDA, 35.9% versus 22.9% of patients [P = 0.005]), and both were significantly greater in the combination therapy group compared with the methotrexate monotherapy group at week 24 (ACR20, 65.0% versus 50.7% of patients [P = 0.005]; MDA, 35.7% versus 22.9% of patients [P = 0.005]). Other secondary outcomes (ACR50 and ACR70 response rates, proportions of patients achieving a Very Low Disease Activity score, and PsA disease activity scores) showed between‐group differences that were consistent with the primary and key secondary end point results. Furthermore, patients in both etanercept treatment arms showed less radiographic progression at week 48 compared with patients who received methotrexate monotherapy. Outcomes were similar in the combination therapy and etanercept monotherapy groups, except for some skin end points. No new safety signals were seen. Conclusion: Etanercept monotherapy and combination therapy with etanercept and methotrexate showed greater efficacy than methotrexate monotherapy in patients with PsA, according to the ACR and MDA response rates and extent of radiographic progression at follow‐up. Overall, combining methotrexate and etanercept did not improve the efficacy of etanercept

Clinical Examination, Ultrasound and MRI Imaging of The Painful Elbow in Psoriatic Arthritis and Rheumatoid Arthritis: Which is Better, Ultrasound or MR, for Imaging Enthesitis?

Introduction: The purpose of the current study was to examine the painful elbow, and in particular enthesitis, in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) using clinical examination, ultrasonography (US) and magnetic resonance imaging (MRI). Methods: Patients with elbow pain (11 with PsA and 9 with RA) were recruited. Clinical examination, US and MRI studies were performed on the same day. For enthesitis, the common extensor and flexor insertions and the triceps insertion were imaged (20 patients, giving a total of 60 sites with comparative data). Imaging was performed with the radiologists blinded to the diagnosis and clinical findings. US was used to assess ‘inflammatory activity’ (Power Doppler signal, oedema, tendon thickening and bursal swelling) and ‘damage’ (erosions, cortical roughening and enthesophytes). MRI was used to assess ‘inflammation’ (fluid in paratenon, peri-entheseal soft-tissue oedema, entheseal enhancement with gadolinium, entheseal oedema and bone oedema) and ‘damage’ (erosion, cortical roughening and enthesophyte). Results: Complete scan data were not available for all patients as one patient could not tolerate the MRI examination. No significant differences in imaging scores were found between PsA and RA. Analysis of damage scores revealed complete agreement between US and MRI data in 43/55 (78%) comparisons; in 10/55 (18%) cases the US data were abnormal but the MRI data normal; in 2/55 (4%) cases, the MRI data were abnormal and the US data normal. Analysis of the inflammation scores revealed complete agreement between US and MRI data in 33/55 (60%) comparisons; in 3/55 (5%) cases US data were abnormal but MRI data normal; in 19/55 (35%) cases the MRI data were abnormal and the US data normal. There was a poor relationship between assessments based on clinical examination and imaging studies. Readers could not accurately identify the disease from imaging findings. Conclusion: Based on our results, at the elbow, US and MR have different roles in assessing enthesitis, with US apparently the better diagnostic tool for assessing damage and MR the better tool for assessing inflammation. In this study enthesitis and synovitis in the painful elbow were found equally in cases of established RA and PsA

Large-scale, prospective, observational studies in patients with psoriasis and psoriatic arthritis: A systematic and critical review

<p>Abstract</p> <p>Background</p> <p>Observational studies, if conducted appropriately, play an important role in the decision-making process providing invaluable information on effectiveness, patient-reported outcomes and costs in a real-world environment. We conducted a systematic review of large-scale, prospective, cohort studies with the aim of (a) summarising design characteristics, the interventions or aspects of the disease studied and the outcomes measured and (b) investigating methodological quality.</p> <p>Methods</p> <p>We included prospective, cohort studies which included at least 100 adults with psoriasis or psoriatic arthritis. Studies were identified through searches in electronic databases (Pubmed, Medline, Cochrane library, Centre for Reviews and Dissemination). Information on study characteristics were extracted and tabulated and quality assessment, using a checklist of 18 questions, was conducted.</p> <p>Results</p> <p>Thirty five papers covering 16 cohorts met the inclusion criteria. There were ten treatment-related studies, only two of which provided a comparison between treatments, and six non-treatment studies which examined a number of characteristics of the disease including mortality, morbidity, cost of illness and health-related quality of life. All studies included a clinical outcome measure and 11 included patient-reported outcomes, however only two studies reported information on patient utilities and two on costs. The quality of the assessed studies varied widely. Studies did well on a number of quality assessment questions including having clear objectives, documenting selection criteria, providing a representative sample, defining interventions/characteristics under study, defining and using appropriate outcomes, describing results clearly and using appropriate statistical tests. The quality assessment criteria least adhered to involved questions regarding sample size calculations, describing potential selection bias, defining and adjusting for confounders and losses to follow-up, and defining and describing a comparison group.</p> <p>Conclusion</p> <p>The review highlights the need for well designed prospective observational studies on the effectiveness, patient-reported outcomes and economic impact of treatment regimes for patients with psoriasis and psoriatic arthritis in a real-world environment.</p