The use of psoriasis biomarkers, including trajectory of clinical response, to predict clearance and remission duration to UVB phototherapy

Abstract

Background Remission duration and treatment response following phototherapy for psoriasis are highly variable and factors influencing these are poorly understood. Objectives Our primary outcome was to investigate whether selected clinical/serum biomarkers were associated with remission duration, and secondly with psoriasis clearance at the end of phototherapy. In addition, we looked at whether early trajectory of UVB clearance was associated with final clearance outcome. MethodsWe performed a prospective cohort study of 100 psoriasis patients, routinely prescribed Narrowband UVB and measured selected clinical and biochemical biomarkers, including weekly PASI (psoriasis area and severity index) scores. Patients were followed up for 18 months. ResultsThe median time to relapse was 6 months (95% CI 5-18) if PASI90 was achieved, and 4 months (95% CI 3-9) if less than PASI90 was achieved. Achieving PASI100 did not result in prolonged remission. On UVB completion, the median final PASI (n = 96) was 1.0 (IQR 0.5, 1.6) with 78 (81%) achieving PASI75 and 39 (41%) achieving PASI90.Improved PASI90 response was significantly associated with lower BMI, higher baseline PASI, non-smoking status and lower cumulative NbUVB. Serum levels of C-reactive protein (CRP) and vitamin D were not associated with clearance or remission duration. Early treatment response from weeks 2-3 was predictive of final outcome. For example, achieving PASI30 at week 3 was significantly associated with PASI90 at the end of the course [36/77 (51%) vs. 2/24 (8%), P < 0.001].Conclusions Raised BMI and positive smoking status predicted poorer phototherapy response. For the first time, we have shown that PASI clearance trajectory over the first 2-3 weeks of UVB, can predict psoriasis clearance. This is an important new step towards developing psoriasis personalized prescribing, which can now be formally tested in clinical trials. These simple clinical measures can be used to inform patient treatment expectations; allowing treatment modifications and/or switching to alternative therapies.

Individualised computational modelling of immune mediated disease onset, flare and clearance in psoriasis

“…Our model predicts complete clearance and eventual remission when the model dynamics drops below the "transition" steady state (i.e., at approximately 90% clearance). These data are consistent with recent findings in a prospective study of 100 patients in which achievement of PASI90 (i.e., at least 90% improvement over their initial PASI) pointed to longer remission [43]. However, not all patients achieving PASI90 progress to complete clearance and/or remission.…”

Individualised computational modelling of immune mediated disease onset, flare and clearance in psoriasis

“…An example of UVB dosimetry is shown in Figure 2a Our model predicts complete clearance and eventual remission when the model dynamics drops below the "transition" steady state (i.e., at approximately 90% clearance). These data are consistent with recent findings in a prospective study of 100 patients in which achievement of PASI90 (i.e., at least 90% improvement over their initial PASI) pointed to longer remission [57]. However, not all patients achieving PASI90 progress to complete clearance and/or remission.…”

“…However, it is unclear whether the model and its class characterisation are powerful enough to predict individual patient outcome. In a recent paper [57], we report the development of a machine learning approach combined with a logistic regression model to predict final PASI using the first 2-3 weeks of PASI measurements during UVB phototherapy. Thus, compared to previous publications, notable advances of our model reported herein are the flexibility to be personalisable at the individual subject level with a single parameter (UVB sensitivity), the possibility to include flares during the therapy (via an extra parameter mimicking a transient immune stimulus), and the ability to capture the PASI dynamics during phototherapy in a way indistinguishable from actual PASI measurements in clinical practice.…”

“…These data are consistent with recent findings in a prospective study of 100 patients in which achievement of PASI90 ( i . e ., at least 90% improvement over their initial PASI) pointed to longer remission [57]. However, not all patients achieving PASI90 progress to complete clearance and/or remission.…”

“…Patient data Our clinical data are derived from a prospective cohort of 94 patients receiving narrowband UVB therapy for psoriasis, recruited at the Royal Victoria Infirmary, Newcastle upon Tyne (UK). The dataset is described fully in [57] but in brief it includes serial weekly patients' PASI measurements (median 7; range 4-11), corresponding serial UVB doses (median 24; range 4-11), delivered 3 times a week together with data on time to relapse and PASI at relapse, collected for up to 18 months. Out of 94 patients, 6 subjects did not relapse within the 18-month monitoring period, and 26 individuals were lost to follow-up.…”