Patient characteristics associated with clinically coded long COVID: an OpenSAFELY study using electronic health records (preprint)

Despite reports of post-COVID-19 syndromes (long COVID) are rising, clinically coded long COVID cases are incomplete in electronic health records. It is unclear how patient characteristics may be associated with clinically coded long COVID. With the approval of NHS England, we undertook a cohort study using electronic health records within the OpenSAFELY-TPP platform in England, to study patient characteristics associated with clinically coded long COVID from 29 January 2020 to 31 March 2022. We estimated age-sex adjusted hazard ratios and fully adjusted hazard ratios for coded long COVID. Patient characteristics included demographic factors, and health behavioural and clinical factors. Among 17,986,419 adults, 36,886 (0.21%) were clinically coded with long COVID. Patient characteristics associated with coded long COVID included female sex, younger age (under 60 years), obesity, living in less deprived areas, ever smoking, greater consultation frequency, and history of diagnosed asthma, mental health conditions, pre-pandemic post-viral fatigue, or psoriasis. The strength of these associations was attenuated following two-dose vaccination compared to before vaccination. The incidence of coded long COVID was higher after hospitalised than non-hospitalised COVID-19. These results should be interpreted with caution given that long COVID was likely under-recorded in electronic health records.

Risk factors for severe COVID-19 outcomes: a study of immune-mediated inflammatory diseases, immunomodulatory medications, and comorbidities in a large US healthcare system (preprint)

Background COVID-19 outcomes, in the context of immune-mediated inflammatory diseases (IMIDs), are incompletely understood. Reported outcomes vary considerably depending on the patient population studied. It is essential to analyse data for a large population, while considering the effects of the pandemic time period, comorbidities, long term use of immunomodulatory medications (IMMs), and vaccination status. Methods In this retrospective case-control study, patients of all ages with IMIDs were identified from a large U.S. healthcare system. COVID-19 infections were identified based on SARS-CoV-2 NAAT test results. Controls without IMIDs were selected from the same database. Severe outcomes were hospitalisation, mechanical ventilation (MV), and death. We analysed data from 1 March 2020 to 30 August 2022, looking separately at both pre-Omicron and Omicron predominant periods. Factors including IMID diagnoses, comorbidities, long term use of IMMs, and vaccination and booster status were analysed using multivariable logistic regression (LR) and extreme gradient boosting (XGB). Findings Out of 2 167 656 patients tested for SARS-CoV-2, there were 290 855 with confirmed COVID-19 infection: 15 397 patients with IMIDs and 275 458 controls (patients without IMIDs). Age and most chronic comorbidities were risk factors for worse outcomes, whereas vaccination and boosters were protective. Patients with IMIDs had higher rates of hospitalisation and mortality compared with controls. However, in multivariable analyses, few IMIDs were rarely risk factors for worse outcomes. Further, asthma, psoriasis and spondyloarthritis were associated with reduced risk. Most IMMs had no significant association, but less frequently used IMM drugs were limited by sample size. XGB outperformed LR, with the AUROCs for models across different time periods and outcomes ranging from 0.77 to 0.92. Interpretation For patients with IMIDs, as for controls, age and comorbidities were risk factors for worse COVID-19 outcomes, whereas vaccinations were protective. Most IMIDs and immunomodulatory therapies were not associated with more severe outcomes. Interestingly, asthma, psoriasis and spondyloarthritis were associated with less severe COVID-19 outcomes than those expected for the population overall. These results can help inform clinical, policy and research decisions. Funding Pfizer, Novartis, Janssen, NIH

Immunogenicity, efficacy, and safety of CoronaVac and Pfizer/BioNTech mRNA vaccines in patients with psoriasis receiving systemic therapies: A prospective cohort study.

BACKGROUND AND OBJECTIVES: Evidence of immune response to COVID-19 vaccine in psoriasis patients on biological agents is lacking. This study aimed to evaluate SARS-CoV-2 antibody levels following vaccination with CoronaVac or Pfizer/BioNTech mRNA in patients using biological agents or methotrexate, high-titer antibody levels achievement rate, and impact of medications on immunogenicity. METHODS: This noninterventional, prospective cohort study included 89 patients and 40 controls vaccinated with two doses of inactivated (CoronaVac) or Pfizer/BioNTech mRNA vaccines. Anti-spike and neutralising antibodies were analysed before and three to six weeks after the second dose. Adverse effects and symptomatic COVID-19 were assessed. RESULTS: Median anti-spike and neutralising antibody titers after CoronaVac were significantly lower in patients than controls (57.92 U/mL vs 125.4 U/mL, and 1/6 vs 1/32, respectively, p < 0.05). Patients were less likely to achieve high-titer anti-spike antibody levels (25.6 % vs 50 %). Infliximab was associated with attenuated vaccine response. Pfizer/BioNTech vaccine induced comparable median anti-spike (2,080 U/mL vs 2,976.5 U/mL,) and neutralising antibody levels (1/96 vs 1/160) in patients and controls, respectively (p > 0.05). High-titer anti-spike and neutralising antibodies development rates were comparable among patients and controls (95.2 % vs 100 %, and 30.4 % vs 50.0 %, respectively, p > 0.05). Nine (10.1 %) COVID-19 cases- all mild - were identified. Psoriasis flare was seen in 6.74 %, mostly after Pfizer/BioNTech vaccine. CONCLUSION: Psoriasis patients treated with biological agents and methotrexate developed similar response to mRNA vaccine but weaker response to inactivated vaccine. Infliximab reduced response to the inactivated vaccine. Adverse effects were more frequent with mRNA vaccine, but none was severe.

Characteristics associated with poor COVID-19 outcomes in people with psoriasis, psoriatic arthritis and axial spondyloarthritis: data from the COVID-19 PsoProtect and Global Rheumatology Alliance physician-reported registries.

OBJECTIVES: To investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death. ORs were estimated using multivariable ordinal logistic regression. RESULTS: Of 5045 cases, 18.3% had PsO, 45.5% PsA and 36.3% axSpA. Most (83.6%) were not hospitalised, 14.6% were hospitalised and 1.8% died. Older age was non-linearly associated with COVID-19 severity. Male sex (OR 1.54, 95% CI 1.30 to 1.83), cardiovascular, respiratory, renal, metabolic and cancer comorbidities (ORs 1.25-2.89), moderate/high disease activity and/or glucocorticoid use (ORs 1.39-2.23, vs remission/low disease activity and no glucocorticoids) were associated with increased odds of severe COVID-19. Later pandemic time periods (ORs 0.42-0.52, vs until 15 June 2020), PsO (OR 0.49, 95% CI 0.37 to 0.65, vs PsA) and baseline exposure to TNFi, IL17i and IL-23i/IL-12+23i (OR 0.57, 95% CI 0.44 to 0.73; OR 0.62, 95% CI 0.45 to 0.87; OR 0.67, 95% CI 0.45 to 0.98; respectively; vs no disease-modifying antirheumatic drug) were associated with reduced odds of severe COVID-19. CONCLUSION: Older age, male sex, comorbidity burden, higher disease activity and glucocorticoid intake were associated with more severe COVID-19. Later pandemic time periods, PsO and exposure to TNFi, IL17i and IL-23i/IL-12+23i were associated with less severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with PsO, PsA and axSpA during COVID-19 waves or similar future respiratory pandemics.

Current developments and perspectives in psoriasis.

The study of psoriasis has yielded fundamental new insights into immunologic regulation and innovative therapies in a way that few other diseases have. In this review, we summarize the main features of current psoriasis research with emphasis on pathophysiological processes and the milestones in the approval of various biologics and small molecule drugs. Thus, through psoriasis research, we are gaining a better understanding of the interplay between the components of the innate and adaptive immune systems. New therapeutics interfere with crucial regulatory networks. Based on current knowledge, we outline what we believe to be some of the most important future research directions and therapeutic and clinical developments in psoriasis. These span multiple areas, ranging from the study of genetic, epigenetic, cellular, and immunological mechanisms to studies of particular clinical forms of psoriasis, individual systemic effects of the disease and its treatment, and the incorporation of large connected data sets and artificial intelligence. The goal is to understand psoriasis holistically, from the molecular to the organismic and societal levels, in order to develop individualized prevention and treatment strategies. Despite impressive progress, psoriasis research must continue to evolve at both the smallest and largest scales to comprehensively address the needs of both physicians and patients.

Clinical course of psoriasis patients that discontinued biologics during the COVID-19 pandemic.

BACKGROUND: Since psoriasis is a chronic disease, it is not recommended to discontinue the treatment agents used. However, in real life, the treatment of psoriasis patients may be interrupted for various reasons. During the pandemic period, the treatment of many patients was also interrupted. OBJECTIVES: To evaluate relapse and clinical worsening in psoriasis patients whose biological therapy was interrupted during the pandemic and reveal associated factors. METHODS: The study included patients aged ≥18 years, who were followed up with moderate and severe chronic psoriasis controlled by the last biological agent [Psoriasis Area Severity Index (PASI) 75 response achieved] but had to discontinue their treatment during the pandemic. The patients' demographic and clinical characteristics, clinical course after the discontinuation of these agents, presence of clinical worsening, and relapse were evaluated. Risk factors were analyzed with the logistic regression analysis. RESULTS: The study included 169 patients, with a mean age of 47.3 ± 14.5 (18-87) years. The mean biologics-free time was 18.2 ± 12.3 (2-56) weeks. Clinical worsening was detected in 41.4% and relapse in 48.5% of the patients. The significant risk factors for clinical worsening and relapse in both univariate and multivariate analyses were alcohol use during the biologics-free period, total time off biologics, and the presence of an additional triggering factor. The use of secukinumab and ustekinumab was found to be a protective factor against clinical worsening in multivariate analyses. CONCLUSION: As the biologics-free period is prolonged, the likelihood of clinical worsening and relapse increases, therefore, we do not recommend discontinuing biological agents.

Brodalumab: 4-Year US Pharmacovigilance Report.

Brodalumab is an interleukin-17 receptor A antagonist approved for the treatment of moderate-to-severe psoriasis in adults without response or with loss of response to other systemic therapies. Brodalumab carries a boxed warning in the United States regarding suicidal ideation and behavior, though no causal relationship has been established. Here, we summarize 4 years of pharmacovigilance data, from August 15, 2017, through August 14, 2021, reported to Ortho Dermatologics by US patients and healthcare providers. The most common AEs listed in the brodalumab package insert (incidence ≥1%) and AEs of special interest are described. Brodalumab exposure estimates were calculated using the time between the first prescription-dispensing authorization date and last prescription-dispensing authorization date. Data were collected from 4019 patients with an estimated brodalumab exposure of 4563 patient-years. The most common AE was arthralgia (115 events; 2.52 events per 100 patient-years). No completed suicides and no new suicidal attempts were reported. There were 102 cases with serious infections; however, no serious fungal infections (including no new cases of oral candidiasis) were reported. There were 26 COVID-19 cases, and 3 of the cases with comorbid conditions were fatal. There were no new cases of Crohn’s disease. Of 37 reported malignancies among 32 cases, none were deemed related to brodalumab. Four-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and 3-year pharmacovigilance data. J Drugs Dermatol. 2023;22(4) doi:10.36849/JDD.7344 Citation: Lebwohl M, Koo J, Leonardi C, et al. Brodalumab: 4-Year US pharmacovigilance report. J Drugs Dermatol. 2023;22(4):419-422. doi:10.36849/JDD.7344.

Nonadherence to systemic immune-modifying therapy in people with psoriasis during the COVID-19 pandemic: findings from a global cross-sectional survey.

BACKGROUND: Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic. OBJECTIVES: To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence. METHODS: Online self-report surveys (PsoProtectMe), including validated screens for anxiety and depression, were completed globally during the first year of the pandemic. We assessed the association between anxiety or depression and nonadherence to systemic immune-modifying therapy using binomial logistic regression, adjusting for potential cofounders (age, sex, ethnicity, comorbidity) and country of residence. RESULTS: Of 3980 participants from 77 countries, 1611 (40.5%) were prescribed a systemic immune-modifying therapy. Of these, 408 (25.3%) reported nonadherence during the pandemic, most commonly due to concerns about their immunity. In the unadjusted model, a positive anxiety screen was associated with nonadherence to systemic immune-modifying therapy [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.07-1.76]. Specifically, anxiety was associated with nonadherence to targeted therapy (OR 1.41, 95% CI 1.01-1.96) but not standard systemic therapy (OR 1.16, 95% CI 0.81-1.67). In the adjusted model, although the directions of the effects remained, anxiety was not significantly associated with nonadherence to overall systemic (OR 1.20, 95% CI 0.92-1.56) or targeted (OR 1.33, 95% CI 0.94-1.89) immune-modifying therapy. A positive depression screen was not strongly associated with nonadherence to systemic immune-modifying therapy in the unadjusted (OR 1.22, 95% CI 0.94-1.57) or adjusted models (OR 1.14, 95% CI 0.87-1.49). CONCLUSIONS: These data indicate substantial nonadherence to immune-modifying therapy in people with psoriasis during the pandemic, with attenuation of the association with mental health after adjusting for confounders. Future research in larger populations should further explore pandemic-specific drivers of treatment nonadherence. Clear communication of the reassuring findings from population-based research regarding immune-modifying therapy-associated adverse COVID-19 risks to people with psoriasis is essential, to optimize adherence and disease outcomes.

The impact of the COVID-19 surge on phototherapy in Taiwan: Focusing on the patient profile, adherence, and attitude before and after the surge.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has caused changes in the medical practice. However, it is unclear whether the patients receiving phototherapy for their dermatoses have been affected. OBJECTIVES: This study aimed to identify the impact of the COVID-19 pandemic on phototherapy, focusing on the patient profile, adherence, and attitude before and after the surge. METHODS: The study encompassed the time 5 months prior to and after the surge of the COVID-19 pandemic (from May to July, 2021), resulting in the temporary closure of our phototherapeutic unit. RESULTS: Nine hundred eighty-one patients received phototherapy during this period. Vitiligo, psoriasis (Ps), and atopic dermatitis (AD) represented the groups with the highest patient numbers. For vitiligo, Ps and AD, 39.6%, 41.9%, and 28.4% of the patients resumed phototherapy after the pandemic-related shutdown (PRS). No significant difference was noted in age, gender, and number of weekly sessions between those who resumed or stopped phototherapy after PRS among three groups. Patients who resumed phototherapy after PRS tended to receive more weekly sessions of phototherapy than those who initiated after PRS. Additionally, patients who resumed phototherapy showed no significant difference in the number of weekly sessions before and after PRS. CONCLUSIONS: This study reveals a significant impact of the COVID-19 pandemic on patients undergoing phototherapy. Although the patient number remained similar before and after PRS, a significant portion of patients discontinued phototherapy after PRS. New strategies and continued education are needed to improve patient management in times of pandemic.

Do different platforms of coronavirus vaccines have different impacts on psoriasis flares?

This study evaluated the impacts on psoriasis flares of 3 vaccine platforms: inactivated, viral vector and mRNA. Respectively, 198 and 96 psoriasis patients with and without COVID-19 vaccination during the study period. Group comparison revealed no increased risk of psoriasis flaring after COVID-19 vaccination. The vaccinated group received 425 doses of vaccine (140 inactivated, 230 viral vector and 55 mRNA). Patients' self-reported symptoms included all three platforms causing psoriasis flare, but the highest was among patients administered with mRNA vaccines. Most flares were mild to moderate, and most patients (89.8%) managed their flare-up lesions without rescue therapy. In conclusion, our study showed that the rate of psoriasis flare was not significantly different between vaccinated and unvaccinated groups. Factors that might explain psoriasis flare include vaccine-related psychological stress and side effects from vaccination. Different platforms of corona vaccines seemed to have different impact of psoriasis flares. Based on our results and the recommendations of several consensus guidelines, the benefits of COVID vaccinations outweigh the risks to patients with psoriasis. Patients with psoriasis should receive a COVID vaccine as soon as one is available.

Incidence and Prognosis of COVID-19 in Patients with Psoriasis: A Multicenter Prospective Study from the Eastern Black Sea Region of Turkey.

COVID-19 infection can have a poor prognosis, especially in patients with chronic diseases and those receiving immunosuppressive or immunomodulating therapies. This study aimed to investigate the severity of COVID-19 infection in patients with psoriasis and compare the infection severity for systemic treatments and comorbidities. We conducted a study in the dermatology clinics of five different centers in the Eastern Black Sea region of Turkey. Four hundred and eighty-eight patients were included, and 22.5% were confirmed as having COVID-19 infection. In our study, the frequency of hospitalization rates due to COVID-19 infection were similar (15.4%, 25.9% respectively) in patients receiving biological treatment and receiving non-biological systemic treatment (P=0.344). Hospitalization rates were higher in patients with hypertension, androgenetic alopecia, and acitretin use (P=0.043, P=0.028, P=0.040). In conclusion, current biologic treatments and non-biologic systemic treatments in patients with psoriasis did not appear to increase the risk of the severe form of COVID-19, except for acitretin.

Roles of Infection in Psoriasis.

Psoriasis is a chronic, immune-mediated disorder with cutaneous and systemic manifestations. Genetic predisposition, environmental factors, and immune dysfunction all contribute to the pathogenesis of psoriasis with host-microbe interaction governing the progression of this disease. Emerging evidence has indicated that infection is an environmental trigger for psoriasis and plays multiple roles in its maintenance as evidenced by the frequent association between guttate psoriasis onset and acute streptococcal infection. Different infectious factors act on immune cells to produce inflammatory cytokines that can induce or aggravate psoriasis. In addition to bacterial infections, viral and fungal infections have also been shown to be strongly associated with the onset or exacerbation of psoriasis. Intervention of skin microbiota to treat psoriasis has become a hot research topic. In this review, we summarize the effects of different infectious factors (bacteria, viruses, and fungi) on psoriasis, thereby providing insights into the manipulation of pathogens to allow for the identification of improved therapeutic options for the treatment of this condition.

A review of disease burden and clinical management for generalized pustular psoriasis in China.

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare, severe, immune-mediated and potentially life-threatening skin disease. The rarity, differential diagnoses, relapsing nature, skin and systemic symptoms, complications and limited therapeutic approaches for this disease pose a clinical and psychological burden on patients and their families. AREAS COVERED: Epidemiologic data of GPP in Chinese patients, including the disease prevalence and age of disease onset, as well as epidemiologic data in global populations were reviewed. Multiple proinflammatory cytokines are involved in the disease development and clinical presentation of GPP and the interleukin (IL)-36-mediated signaling pathway play a central role. Furthermore, loss-of-function mutations in IL-36 RN (encoding the IL-36 receptor antagonist) are associated with GPP, suggesting a potential drug target for developing a disease-specific therapeutic approach. Biologic agents, including IL-36 R targeted agents, are promising treatment options, especially as existing conventional therapies are inadequate. Chinese guidelines for the diagnosis and treatment of psoriasis recommend systemic and topical treatment options for GPP and disease complications, as well as for GPP during pregnancy and juvenile GPP. EXPERT OPINION: This review summarizes the epidemiology, pathogenesis, clinical characteristics, disease burden and management of patients with GPP in China, and also describes future treatment targets and related clinical trials.