Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT).

BACKGROUND: Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease that affects the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1. OBJECTIVES: To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in PPP. METHODS: This was a randomized (1 : 1), double-blind, two-staged, adaptive, UK multicentre, placebo-controlled trial [ISCRTN13127147 (registered 1 August 2016); EudraCT number: 2015-003600-23 (registered 1 April 2016)]. Participants had a diagnosis of PPP (> 6 months) requiring systemic therapy. Treatment was 8 weeks of anakinra or placebo via daily, self-administered subcutaneous injections. Primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. RESULTS: A total of 374 patients were screened; 64 were enrolled (31 in the anakinra arm and 33 in the placebo arm) with a mean (SD) baseline PPPASI of 17·8 (10·5) and a PPP investigator's global assessment of severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in the intention-to-treat analysis [-1·65, 95% confidence interval (CI) -4·77 to 1·47; P = 0·30]. Similarly, secondary objective measures, including fresh pustule count (2·94, 95% CI -26·44 to 32·33; favouring anakinra), total pustule count (-30·08, 95% CI -83·20 to 23·05; favouring placebo) and patient-reported outcomes, did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect for an individual who received ≥ 90% of the total treatment (48% in the anakinra group) was -3·80 (95% CI -10·76 to 3·16; P = 0·285). No serious adverse events occurred. CONCLUSIONS: No evidence for the superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP.

Risk-mitigating behaviours in people with inflammatory skin and joint disease during the COVID-19 pandemic differ by treatment type: a cross-sectional patient survey.

BACKGROUND: Registry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID-19) outcomes compared with patients receiving no systemic treatments. OBJECTIVES: We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. METHODS: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk-mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed-effects model. RESULTS: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk-mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35-1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23-1·56). Shielding was associated with established risk factors for severe COVID-19 [male sex (OR 1·14, 95% CI 1·05-1·24), obesity (OR 1·37, 95% CI 1·23-1·54), comorbidity burden (OR 1·43, 95% CI 1·15-1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27-1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36-1·80). Modest differences in the proportion shielding were observed across nations. CONCLUSIONS: Greater risk-mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence-based patient communication on risk-mitigation strategies and may help inform updated public health guidelines as the pandemic continues.

Research priorities and identification of a health-service delivery model for psoriasis from the UK Psoriasis Priority Setting Partnership.

BACKGROUND: Psoriasis impacts the health and psychosocial functioning of patients, conferring a significant economic burden on healthcare systems. There remain unmet needs in psoriasis care, which if addressed by research, could improve clinical outcomes. AIM: To research priorities and identify a health service delivery model from the UK Psoriasis Priority Setting Partnership (PsPSP). METHODS: Between July 2017 and November 2018, we invited people with lived experience of psoriasis and healthcare professionals to (i) identify unmet needs, and (ii) prioritize the order in which these should be addressed by research. We collaborated with the Psoriasis Association and used methodology established by the James Lind Alliance, which pioneers the joint setting of research priorities by patients and clinicians worldwide. RESULTS: In our initial harvesting survey (Survey 1), 2133 questions were submitted by 805 individuals. Submissions that had not been answered by research (true uncertainties) were supplemented with evidence gaps from systematic reviews/guidelines published in the previous 5 years and refined to produce 55 indicative questions. Voting in Survey 2, by 1154 individuals, enabled a shortlist of questions, which were prioritized during the final workshop to produce a top 20 list of research questions. Submissions on health service delivery (5.8% of the total submissions), which were analysed separately, described a blueprint for psoriasis care. CONCLUSIONS: The PsPSP will inform the translational research agenda, ensuring that future research is relevant for the needs of people with psoriasis and those who manage the disease. Submissions on health service delivery describe a model of holistic, patient-focused care providing high-quality, effective management for patients with psoriasis.

Comparing preferences for outcomes of psoriasis treatments among patients and dermatologists in the U.K.: results from a discrete-choice experiment.

BACKGROUND: Plaque psoriasis can have a significant negative effect on patients' quality of life, and treatments can result in serious toxicities. Although there have been several studies of patients' and physicians' relative preferences for the benefits and risks of psoriasis treatments, it is unclear how and whether patients' and physicians' preferences for the outcomes of psoriasis treatments differ. OBJECTIVES: To quantify patient and dermatologist preferences for improvements in psoriasis symptoms and for increases in the risk of treatment-related serious adverse events. METHODS: Members of the U.K. Psoriasis Association and U.K. dermatologists with experience prescribing biologics completed a web-enabled discrete-choice experiment survey in which they evaluated efficacy and safety features of biological treatments for psoriasis. Choices between hypothetical treatment options were used to estimate preference weights indicating respondents' relative trade-off preferences among treatment outcomes. These outcomes included improvements in the severity and coverage of psoriatic plaques and treatment-related risks of tuberculosis, serious infections and lymphoma. Preference estimates were used to derive the maximum level of side-effect risks that respondents would accept for improvements in psoriasis symptoms. RESULTS: Respondents' tolerance for side-effect risks varied with side-effect severity and location of plaques, and risk tolerance for serious side-effects was greater for patients than for dermatologists. CONCLUSIONS: Estimates of patients' risk tolerance for serious side-effects indicate that patients valued psoriasis symptom control highly and suggest that psoriasis symptoms have a significant effect on patients' quality of life. In light of research showing increased treatment satisfaction and improved treatment adherence among patients who receive therapies that are consistent with their preferences, our findings suggest that greater communication between dermatologists and patients about risk tolerance could help improve patient care.

Psoriasis: snapshots of the unspoken: using novel methods to explore patients' personal models of psoriasis and the impact on well-being.

BACKGROUND: People with psoriasis report high levels of undermanaged distress. This is compounded by the problem that some patients find it difficult to discuss their emotions. Distress prevents optimal self-management, which may exacerbate psoriasis flares, thereby creating a vicious cycle. OBJECTIVES: To offer people with psoriasis a novel way of expressing their personal models of psoriasis in order to gain a better understanding of their experiences of living with the condition. METHODS: We used a qualitative technique - asking people with psoriasis to complete a postcard entitled 'Dear Psoriasis...' - to collect survey data on their personal models of psoriasis. RESULTS: One hundred and four returned postcards provided new insights into the extent of and reasons for distress in psoriasis. Seven dominant themes emerged: identity and relationships; battleground; control; emotional consequences; hypervigilance; coping; treatment burden. CONCLUSIONS: Reports of distress were common, and for many it was long-standing. Some reported low self-esteem and self-denigration bordering on self-loathing, and described being hypervigilant and in a constant battle with their skin. Many people did not expect to have intimate relationships, resulting in reduced social support for patients in the future. This research underscores the need for patient support and psychological treatment to be made available as part of routine care.

Extending psychosocial assessment of patients with psoriasis in the UK, using a self-rateds, web-based survey.

BACKGROUND: Quality of life self-rating using a web-based survey has not previously been evaluated for psoriasis in the UK. AIM: To use an open-access web-based survey to assess the effect of psoriasis on patients' daily life. Methods. The survey was conducted using a dedicated website endorsed by a UK psoriasis patient charity. RESULTS: In total, 1760 patients (1102 women, 658 men; median age range 40-44 years) assessed their psoriasis using the website. Psoriasis was 'very' or 'extremely' active in 52%, and 71% had been diagnosed > 10 years previously. Psoriasis had negatively affected the working life of 59% of patients, and the educational performance of 31%. CONCLUSIONS: The use of an open-access web-based survey may address potential bias in previous studies, but may itself introduce a bias towards younger patients. This is the first report of a web-based survey of UK patients with psoriasis, providing further recent evidence of how psoriasis affects patients' lives.