Psoriasis : observational studies on clinical course, economic burden and treatment

Sammanfattning: Better understanding of long-term prognosis, clinical course, comorbidities, economic burden, and treatment of psoriasis, can improve care of patients with the disease and may inform decisions on resource allocation, benefitting not only patients but also the society in general. The Stockholm Psoriasis Cohort (SPC), Study 1, was initiated to describe the clinical course or psoriasis. The SPC enrolled 721 patients with onset of psoriasis within the last twelve months. 542 (75%) patients had plaque psoriasis and 174 (24%) had guttate psoriasis. Patients were followed in medical records and registers, and among the 686 participants alive after ten years, 546 (80%) responded to a questionnaire and 509 (74%) were also examined clinically. Plaque psoriasis was strikingly persistent. Forty one percent of the patients with severe disease at onset had severe disease at ten years compared with 9% of participants with mild or moderate disease at onset (Relative Risk [RR]=4.3; p<0.001). Guttate onset was associated with a favorable disease course: After ten years, 56/116 (48%) of patients were in remission without treatment and only 1/94 patients with mild or moderate guttate onset had severe psoriasis at ten years. Recursive partitioning analysis identified groups with distinctive risks for severe skin disease and Psoriatic Arthritis (PsA): The cumulative incidence of severe disease in participants with plaque phenotype, at least moderate disease, and scalp psoriasis at onset was 52% (95% Confidence Interval [CI]: 41% to 64%), compared to 11% (95% CI: 8% to 14%) in patients with mild disease at onset. Forty-eight of 82 patients (59%) with peripheral enthesitis at onset had PsA after ten years compared to 37/304 (12%) without arthralgia at onset (p<0.001). Systemic treatment at or before enrolment was associated with reduced risk for severe disease at ten years compared to systemic initiation later (Odds Ratio: 0.24; 95% CI: 0.06 to 0.90). Overall, this study indicates that the course of psoriasis can be predicted with good discriminatory power and that it may be modified by early effective intervention. The latter finding should be confirmed in randomized controlled clinical trials. The second study estimated all-cause and cause-specific mortality in 34,355 patients with mild psoriasis and 4,719 patients with severe psoriasis compared to 154,775 age- sex- and residency matched controls. The study found that patients with mild and severe psoriasis had excess all-cause mortality: Hazard ratio (HR) 1.15 (95% CI: 1.10 to 1.21) for patients with mild psoriasis, and HR 1.56 (95% CI: 1.36 to 1.79) for patients with severe psoriasis. Cardiovascular disease accounted for the largest proportion of excess mortality (48% in mild psoriasis and 33% in severe psoriasis). For patients with mild and severe psoriasis, the causes of death with the highest excess risks were kidney disease (HR: 2.20; 95% CI: 1.36 to 3.56), and liver disease (HR: 4.26; 95% CI: 1.87 to 9.73), respectively. The findings suggest that it may be valuable to screen patients with psoriasis for cardiovascular, kidney, and liver disease. Economic burden of psoriasis in 2010 and potential cost offsets with biologic treatment were estimated in Study 3, using data on 31,043 patients with psoriasis and 111,645 sex-, age- and residency-matched controls. Patients had higher direct and indirect costs compared to controls after adjusting for the Charlson Comorbidity Index (CCI): USD 3,555 versus USD 2,190 (p < 0.001) for direct costs and USD 9,898 versus USD 6,579 (p < 0.001) for indirect costs. Both mean direct and mean indirect costs generally increased with disease severity inferred by most potent treatment received, albeit the increase was not monotonic. Disregarding the costs of biologics, initiation of biologic treatment was estimated to generate one-year direct and indirect cost offsets from USD 1,135 (95% CI: 328 to 2,050) to USD 4,422 (95% CI: 2,771 to 6,552), and USD 774 (95% CI: -535 to 2,019) to USD 1,875 (95% CI: 188 to 3,650), respectively. Collectively, these findings show that psoriasis is associated with substantial direct and indirect costs, which may be modifiable with effective treatment. Study 4 described treatment patterns in 19,103 patients with psoriasis and estimated the oneyear cumulative incidences of treatment events (discontinuation, switch, or augmentation) with topicals, systemics, and biologics at 93%, 72%, and 75%, respectively. Within one year of having discontinued treatment, the cumulative incidences of starting a new treatment was 49% for topicals, 61% for systemics, and 80% for biologics. These findings highlight the unmet needs across the disease spectrum and underscore the chronicity of the disease. Study 5 estimated real-world effectiveness of adalimumab and etanercept compared to methotrexate. After adjusting for confounders, adalimumab had better drug survival (HR: 0.67; 95% CI: 0.51 to 0.88), lower mean predicted PASI (-2.0; 95% CI: -2.6 to -1.5) and DLQI (-0.9; 95% CI: -1.5 to -0.3) during maintenance treatment than methotrexate. The results for the comparison between etanercept and methotrexate were more mixed. These findings support adalimumab as first line systemic treatment for psoriasis, but further data, especially on safety and costs, are needed.