Non-Melanoma Skin Cancer Risk Among Patients in the Psoriasis Longitudinal Assessment and Registry (PSOLAR)

To the Editor: Patients with psoriasis are at increased risk of developing non melanoma skin cancer (NMSC), including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC).1,2 The risk is especially elevated among those who previously received systemic treatment or phototherapy.2 Systemic treatments, including biologic therapies and methotrexate (MTX), are effective in managing immune-mediated diseases; however, they may increase susceptibility to NMSC due to immunosuppression or other factors.3

Depressive symptoms, depression, and the effect of biologic therapy among patients in Psoriasis Longitudinal Assessment and Registry (PSOLAR).

BACKGROUND: Patients with psoriasis are at an increased risk for depression. However, the impact of treatment on this risk is unclear. OBJECTIVE: Evaluate the incidence and impact of treatment on depression among patients with moderate-to-severe psoriasis. METHODS: We defined a study population within the Psoriasis Longitudinal Assessment and Registry and measured the incidence of depressive symptoms (Hospital Anxiety and Depression Scale-Depression score ≥8) and adverse events (AEs) of depression within cohorts receiving biologics, conventional systemic therapies, or phototherapy. Patients were evaluated at approximately 6-month intervals. Multivariate modeling determined the impact of treatment on risk. RESULTS: The incidence rates of depressive symptoms were 3.01 per 100 patient-years (PYs) (95% confidence interval [CI], 2.73-3.32), 5.85 per 100 PYs (95% CI, 4.29-7.97), and 5.70 per 100 PYs (95% CI, 4.58-7.10) for biologics, phototherapy, and conventional therapy, respectively. Compared with conventional therapy, biologics reduced the risk for depressive symptoms (hazard ratio, 0.76; 95% CI, 0.59-0.98), whereas phototherapy did not (hazard ratio, 1.05; 95% CI, 0.71-1.54). The incidence rates for AEs of depression were 0.21 per 100 PYs (95% CI, 0.15-0.31) for biologics, 0.55 per 100 PYs (95% CI, 0.21-1.47) for phototherapy, and 0.14 per 100 PYs (95% CI, 0.03-0.55) for conventional therapy; the fact that there were too few events (37 AEs) precluded modeling. LIMITATIONS: Incomplete capture of depression and confounders in the patients on registry. CONCLUSION: Compared with conventional therapy, biologics appear to be associated with a lower incidence of depressive symptoms among patients with psoriasis.

Gastrointestinal Signs and Symptoms Related to Inflammatory Bowel Disease in Patients With Moderate-to-Severe Psoriasis

Background: Psoriasis (PsO) is a chronic inflammatory skin disorder that may be associated with comorbidities, including inflammatory bowel disease (IBD), given common immunopathogenic mechanisms. Whether PsO patients are more likely to suffer from gastrointestinal (GI) signs and symptoms has not been well-characterized. Understanding their prevalence in PsO patients may inform strategies to evaluate for GI signs and symptoms, screen for those at risk for IBD, and guide choice of therapy. Objective: To assess the prevalence of GI signs and symptoms in patients with moderate-to-severe PsO. Methods: An Internet-based survey was conducted to evaluate GI signs and symptoms in patients with self-reported moderate-to-severe PsO and non-PsO controls. The impact of PsO severity and presence of psoriatic arthritis (PsA) [self-reported and/or screened positive on the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire] on prevalence of GI signs and symptoms was also assessed. The survey included questions about PsO, comorbidities, demographics, and GI signs and symptoms. Questions related to GI signs and symptoms were used to calculate a modified CalproQuest* score to identify patients at increased risk for IBD. Results: Survey responses were collected from 740 PsO patients and 1411 non-PsO controls. With the exception of age, demographics were generally comparable between groups. All six GI signs and symptoms assessed (belly pain, feeling full/bloated, diarrhea, mucus in stool, blood in stool, and unintentional weight loss) were more prevalent in PsO patients compared with non-PsO controls, and a higher proportion of PsO patients also had a positive CalproQuest* result. In addition, both more severe PsO and concomitant PsA were associated with a higher prevalence of GI signs and symptoms and a positive CalproQuest*. Conclusions: This study suggests that PsO patients, including those with PsA, have a higher prevalence of GI signs and symptoms. Physicians should recognize and consider this concern in PsO patient management. J Drugs Dermatol. 2018;17(12):1298-1308.

Dermatologist and Patient Preferences in Choosing Treatments for Moderate to Severe Psoriasis.

INTRODUCTION: The objective of the study was to determine the relative importance (RI) of treatment attributes psoriasis patients and physicians consider when choosing between biologic therapies based on psoriasis severity. METHODS: A discrete choice experiment (DCE) weighting preference for eight sets of hypothetical treatments for moderate or severe psoriasis was conducted. DCE hypothetical treatments were defined and varied on combinations of efficacy, safety, and dosing attributes [frequency/setting/route of administration (ROA)]. RESULTS: When assuming moderate psoriasis in the patient DCE, ROA (RI 29%) and efficacy (RI 27%) drive treatment choices. When assuming severe disease in the DCE, patients preferred treatments with higher efficacy (RI 36%); ROA was relatively less important (RI 15%). From the physician perspective, ROA (RI 32%) and efficacy (RI 26%) were most important for moderate psoriasis patients. In the physician model for severe psoriasis, efficacy (RI 42%) was the predominant driver followed by ROA (RI 22%). Regardless of severity, probability of loss of response within 1 year was the least important factor. CONCLUSIONS: The severity of disease is a critical element in psoriasis treatment selection. There are high levels of alignment between physician- and patient-derived preferences in biologic treatment choice selection for psoriasis. FUNDING: Janssen Pharmaceuticals.

Reliability and convergent validity of two outcome instruments for pemphigus.

A major obstacle in performing multicenter controlled trials for pemphigus is the lack of a validated disease activity scoring system. Here, we assess the reliability and convergent validity of the PDAI (pemphigus disease area index). A group of 10 dermatologists scored 15 patients with pemphigus to estimate the inter- and intra-rater reliability of the PDAI and the recently described ABSIS (autoimmune bullous skin disorder intensity score) instrument. To assess convergent validity, these tools were also correlated with the Physician's Global Assessment (PGA). Reliability studies demonstrated an intra-class correlation coefficient (ICC) for inter-rater reliability of 0.76 (95% confirdence interval (CI)=0.61-0.91) for the PDAI and 0.77 (0.63-0.91) for the ABSIS. The tools differed most in reliability of assessing skin activity, with an ICC of 0.39 (0.17-0.60) for the ABSIS and 0.86 (0.76-0.95) for the PDAI. Intra-rater test-retest reliability demonstrated an ICC of 0.98 (0.96-1.0) for the PDAI and 0.80 (0.65-0.96) for the ABSIS. The PDAI also correlated more closely with the PGA. We conclude that the PDAI is more reproducible and correlates better with physician impression of extent. Subset analysis suggests that for this population of mild-to-moderate disease activity, the PDAI captures more variability in cutaneous disease than the ABSIS.

Factor VIII ectopically expressed in platelets: efficacy in hemophilia A treatment.

Activated platelets release their granule content in a concentrated fashion at sites of injury. We examined whether ectopically expressed factor VIII in developing megakaryocytes would be stored in alpha-granules and whether its release from circulating platelets would effectively ameliorate bleeding in a factor VIIInull mice model. Using the proximal glycoprotein 1b alpha promoter to drive expression of a human factor VIII cDNA construct, transgenic lines were established. One line had detectable human factor VIII that colocalizes with von Willebrand factor in platelets. These animals had platelet factor VIII levels equivalent to 3% to 9% plasma levels, although there was no concurrent plasma human factor VIII detectable. When crossed onto a factor VIIInull background, whole blood clotting time was partially corrected, equivalent to a 3% correction level. In a cuticular bleeding time study, these animals also had only a partial correction, but in an FeCl3 carotid artery, thrombosis assay correction was equivalent to a 50% to 100% level. These studies show that factor VIII can be expressed and stored in platelet alpha-granules. Our studies also suggest that platelet-released factor VIII is at least as potent as an equivalent plasma level and perhaps even more potent in an arterial thrombosis model.