Faculty Bibliography

Background: Despite their impressive efficacy in phase 3 trials, biologic agents for psoriasis (PsO) may lose efficacy over time. The factors associated with loss of efficacy have yet to be fully elucidated. Objective: We aimed to identify factors associated with PsO patients using multiple biologics in comparison to patients who used 1 biologic. We also reviewed the literature comparing the survival of different biologic agents for PsO. Methods: We examined clinical data from 222 psoriasis patients at the University of California San Francisco, of whom 51 reported use of 3 or more biologics and of whom 171 reported use of only a single biologic agent at the time of enrollment into a research database from 2006-2020. This study was IRB-approved at UCSF (#10-02830) and all subjects provided written informed consent. We performed univariate and multivariate regression analysis to identify significant demographic features, clinical features, and co-morbidities associated with multi-biologic use. We performed a literature review of studies comparing psoriasis biologic survival at 1, 2, and 5 years and factors associated with single biologic failure. Results: In univariate analysis, duration of PsO, initial presentation of PsO on the gluteal cleft, erythrodermic psoriasis, and acne were associated with using 3 or more biologics. In multivariate analysis, duration of PsO, erythrodermic psoriasis, and acne remained significant. Our review of biologic survival revealed differences according to biologic class. Conclusion: We identified novel factors associated with multi-biologic use in PsO. Further studies in this area are needed to achieve a precision medicine approach.

OBJECTIVES/OBJECTIVE:To compare work absenteeism and short-term disability among adults with psoriasis or psoriatic arthritis (PsA), versus controls in the USA. METHODS:Adults eligible for work absenteeism and/or short-term disability benefits between 1/1/2009 and 4/30/2020 were screened in the IBM® MarketScan® Commercial and Health and Productivity Management Databases. The following groups were defined: (1) psoriasis: ≥ 2 psoriasis diagnoses ≥ 30 days apart and no PsA diagnoses; (2) PsA: ≥ 2 PsA diagnoses ≥ 30 days apart; (3) control: absence of psoriasis and PsA diagnoses. Controls were matched to psoriasis and PsA patients based on age, gender, index year, and comorbidities. Non-recreational work absences and sick leaves were evaluated in absentee-eligible patients, and short-term disability was evaluated in short-term disability-eligible patients. Costs (in 2019 USD) associated with each type of work absence were evaluated. RESULTS:4261 psoriasis and 616 PsA absentee-eligible and 25,213 psoriasis and 3480 PsA short-term disability-eligible patients were matched to controls. Average non-recreational work absence costs were $1681, $1657, and $1217 for the PsA, psoriasis, and control group, respectively. Compared with psoriasis patients and controls, more PsA patients had sick leaves after 1 year (56.2% versus 55.6% and 41.5%, p < 0.0001). Similarly, short-term disability was more frequent in PsA patients than psoriasis patients and controls at year one (8.8% versus 5.6% and 4.7%, p < 0.0001) and corresponding costs were higher ($605, $406, and $335 on average, p < 0.0001). CONCLUSION/CONCLUSIONS:Annual work absenteeism and short-term disability were consistently greater among patients with PsA and psoriasis than controls, highlighting the substantial economic burden of psoriatic disease. Key points • Patients with PsA had greater short-term disability compared with patients with psoriasis and patients with neither psoriasis nor PsA. • Patients with PsA and patients with psoriasis incurred greater non-recreational work absences and sick leaves than patients with neither psoriasis nor PsA.

Background/Purpose: Obesity is associated with poor response to treatment in patients with psoriatic arthritis (PsA), however, available data are mostly focused on tumor necrosis factor inhibitor (TNFi) initiators with only a few studies that have examined this association with initiators of other therapies. There are even fewer studies with patient reported outcome (PRO) measures as the outcomes of interest in PsA treatment. The clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) is a composite measure of disease activity in PsA and the, Routine Assessment of Patient Index Data 3 (RAPID3) and Psoriatic Arthritis Impact of Disease (PsAID) are PROs used in PsA. We examined the association of obesity with change in cDAPSA, RAPID3, PsAID among patients with PsA initiating TNFi, interleukin 17 inhibitors (IL17i) and oral small molecules (OSM).
Method(s): Patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium longitudinal cohort study in the US between 2016-2020, initiated therapy with either TNFi, IL17i or OSM and completed at least one follow up visit. Treatment response was assessed by change in cDAPSA, RAPID3, or PsAID. Patients were stratified based on body mass index category (normal weight = BMI 19 to < 25 kg/m², overweight = BMI 25 to < 30 kg/m², obese = BMI >= 30 kg/m²). Baseline characteristics were reported descriptively. BMI category and its association with change in the outcomes of interest was examined in univariable and age-and-sex adjusted linear regression models.
Result(s): A total of 310 patients were included in the analysis. The mean age of patients was 52 and 56% were female. At baseline, the mean cDAPSA was 17.3 (SD 12.7), the mean PsAID was 3.6 (SD 2.2), the mean RAPID3 was 10.9 (SD 5.8). Baseline scores were overall similar when stratified by BMI category (Table 1). The mean change in cDAPSA was lowest among obese patients (-2.91 (SD 9.56) in normal BMI, -2.29 (SD 11.48) in overweight BMI, and -1.42 (SD 12.33) in obese BMI). The mean change in RAPID3 was lowest among obese patients (-1.53 (SD 4.50) in normal BMI, -1.69 (SD 4.47) in overweight BMI, and -0.26 (SD 5.46) in obese BMI). The mean change in PsAID was lowest among obese patients (-0.58 (SD 1.48) in normal weight BMI, -0.72 (SD 1.47) in overweight BMI, and -0.17 (SD 1.98) in obese BMI) (Figure 1). These differences were not statistically significant, potentially due to sample size. In unadjusted and age-and-sex adjusted analyses (Table 2), compared to the normal BMI category, obese patients had less improvement in cDAPSA, RAPID3 and PsAID. Similar numerical reduction in improvement was also found in the TNFi initiators although there was not a stepwise decrease in improvement with increasing BMI in IL17i nor OSM initiators.
Conclusion(s): The mean change in the selected outcome measures (cDAPSA, RAPID3, PsAID) was lowest among obese patients compared to the other BMI categories. Interestingly, this pattern was observed primarily among TNFi initiators as opposed to OSM or IL17i initiators (Figure Presented)

Background/Purpose: Patients with immune mediated inflammatory disorders (IMIDs) have an inherently heightened susceptibility to infection and may be considered high risk for developing COVID-19. While data regarding the COVID-19 vaccine's immunogenicity in an immunocompetent adult population is rapidly emerging, the ability of IMID patients to adequately respond to these vaccines is not known. Here, we investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with IMIDs on immunomodulatory treatment Methods: Patients with immune mediated inflammatory disorders (IMIDs) have an inherently heightened susceptibility to infection and may be considered high risk for developing COVID-19. While data regarding the COVID-19 vaccine's immunogenicity in an immunocompetent adult population is rapidly emerging, the ability of IMID patients to adequately respond to these vaccines is not known. Here, we investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with IMIDs on immunomodulatory treatment.
Result(s): The NY cohort baseline characteristics are found in Table 1. The Erlangen cohort consisted of 182 healthy subjects, 11 subjects with IMID receiving TNFi monotherapy, and 20 subjects with IMID on MTX monotherapy. In both cohorts, healthy individuals and those with IMID not on MTX were similar in age, while those IMID patients receiving MTX were generally older. In the NY cohort, of the healthy participants, 96.3% demonstrated adequate humoral immune response. Patients with IMID not on MTX achieved a similar rate of high antibody response rate (91.8%), while those on MTX had a lower rate of adequate humoral response (75.0%) (Figure 1A). This remains true even after the exclusion of patients who had evidence of prior COVID-19 infection (P= 0.014). Of note, 3 out of the 4 IMID patients receiving rituximab did not produce an adequate response. Similarly, in the Erlangen validation cohort, 98.3% of healthy controls, 90.9% of patients with IMID receiving TNFi monotherapy, and 50.0% receiving MTX monotherapy achieved adequate immunogenicity (Figure 1B). These differences remain significant when combining the cohorts, using a stricter definition of adequate response, and in a subgroup analysis by age. Cellular response was also analyzed in a subgroup of the NY cohort before and after second vaccination. Activated CD8+ T cells (CD8+ T cells expressing Ki67 and CD38) and the granzyme B-producing subset of these activated CD8+ T cells, were induced in immunocompetent adults and those with IMID not on MTX, but not induced in patients receiving MTX (Figure 2).
Conclusion(s): In two independent cohorts of IMID patients, MTX, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking MTX to increase the chances of immunization efficacy against SARS-CoV-2, as has been demonstrated for other viral vaccines

Objectives: Absenteeism and work disability substantially contribute to the economic burden of psoriasis and psoriatic arthritis (PsA). This study compared work absenteeism and short-term disability among adults with psoriasis, PsA, and controls with neither psoriasis nor PsA in the United States.
Method(s): Adults eligible forwork absenteeism and/or short-termdisability benefits between 1/1/2009 and 2/29/2020were screened in the IBMMarketScan Commercial and Health and Productivity Management Databases. The following groups were defined: 1) Psoriasis: >=1 inpatient or 2 outpatient psoriasis diagnoses and no PsA diagnoses; 2) PsA: >=1 inpatient or 2 outpatient PsA diagnoses; 3) Control: absence of psoriasis and PsA diagnoses. Controls were matched 3:1 to psoriasis and PsA patients based on age, gender, and comorbidities. Absenteeism, short-term disability, and corresponding costs (in 2019 USD) were evaluated descriptively and through mixed models.
Result(s): 5,785 psoriasis and 1,245 PsA absentee-eligible and 35,512 psoriasis and 7,434 PsA short-term disability eligible patients were matched to the control group. During the first year of follow-up, 9.7% of PsA patients had short-term disability leave versus 6.2% of psoriasis patients and 4.8% of controls (Table 1). The odds of short-term disability at one year were significantly greater among patients with PsA than psoriasis (OR: 1.56, 95% CI: 1.45-1.69) and controls (OR: 1.95, 95% CI: 1.82-2.10). Average costs from non-recreational work absences were $1,891, $1,680, and $1,333 per patient per year for the PsA, psoriasis, and control group, respectively. Costs associated with non-recreationalwork absences and short-term disability were significantly greater for PsA and psoriasis patients than controls at one year (p < 0.0001 for all comparisons). These costs were also significantly greater for PsAthan psoriasis at one year (p = 0.001 and p < 0.0001, respectively). This trend of increased costs for PsA patients compared with the other groups was sustained throughout the five years of follow-up (Figure 1).
Conclusion(s): Work absenteeism and short-term disability were greater among both the psoriasis and PsA groups than the control group. Absenteeism and short-term disability were greater among patients with PsA than psoriasis. These findings demonstrate the substantial impact that psoriatic disease has on patients' work related outcomes, and highlight remaining unmet needs for patients with psoriatic disease

OBJECTIVES:Physical function is a core outcome in PsA. We examined the construct validity and responsiveness of three commonly used instruments to assess physical function in PsA: HAQ disability index (HAQ-DI), MultiDimensional HAQ (MDHAQ) and the Patient-Reported Outcomes Measurement Information System (PROMIS®) Global-10. METHODS:Between 2016 and 2019, patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium longitudinal cohort study in the USA. Correlations were calculated at baseline and among change scores using Spearman's correlation coefficient. Standardized response means were calculated. Agreement with the 20% improvement cut-off was used to determine the potential effect of using MDHAQ or the PROMIS Global-10 physical health (GPH) subscore in place of HAQ-DI when assessing the ACR20. RESULTS:A total of 274 patients were included in the analysis. The mean age of patients was 49 years and 51% were male. At baseline, the mean HAQ-DI was 0.6 (s.d. 0.6; range 0-3), the mean MDHAQ was 1.8 (s.d. 1.6; range 0-10) and the mean GPH T-score was 43.4 (s.d. 9.3; range 0-100). All three instruments were strongly correlated at baseline (rho 0.75-0.85). Change scores were moderately correlated (rho 0.42-0.71). Among therapy initiators, the mean change between two visits in HAQ-DI, MDHAQ and GPH was -0.1 (s.d. 0.4), -0.2 (s.d. 1.2) and 2.5 (s.d. 6.1), respectively. The standardized response means were 0.18, 0.16 and 0.41, respectively. CONCLUSION:The three instruments tested are not directly interchangeable but have overall similar levels of responsiveness.

Objective/UNASSIGNED:To investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. Methods/UNASSIGNED:Established patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response. Results/UNASSIGNED:Although healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination. Conclusions/UNASSIGNED:In two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines. KEY MESSAGES/UNASSIGNED:These results suggest that patients on methotrexate may need alternate vaccination strategies such as additional doses of vaccine, dose modification of methotrexate, or even a temporary discontinuation of this drug. Further studies will be required to explore the effect of these approaches on mRNA vaccine immunogenicity.

The concept of psoriatic arthritis (PsA) prevention is gaining increased interest owing to the physical limitation, poor quality of life and low remission rates that are achieved with current therapies for PsA. The psoriasis-to-PsA transition offers a unique opportunity to identify individuals at increased risk of developing PsA and to implement preventive strategies. However, identifying individuals at increased risk of developing PsA is challenging as there is no consensus on how this population should be defined. This Consensus Statement puts forward recommended terminology from the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) for defining specific subgroups of individuals during the preclinical and early clinical phases of PsA to be used in research studies. Following a three-round Delphi process, consensus was reached for three terms and definitions: 'increased risk for PsA', 'psoriasis with asymptomatic synovio-entheseal imaging abnormalities' and 'psoriasis with musculoskeletal symptoms not explained by other diagnosis'. These terms and their definitions will enable improved identification and standardization of study populations in clinical research. In the future, as increasing evidence emerges regarding the molecular and clinical features of the psoriasis-to-PsA continuum, these terms and definitions will be further refined and updated.