Title: Risk and predictors of infections in psoriasis patients exposed to biologic therapy: a prospective observational cohort study in the British Association of Dermatologists’ Biologic Interventions Register (BADBIR)
Funder: Department of Health and Social Care

Abstract: Background: Biologic therapies are effective immune-modulators that have transformed the management of severe psoriasis. The licensed agents include infliximab, etanercept, adalimumab and ustekinumab. There are concerns that infection risk is increased in psoriasis patients on biologic therapies. Aim: To develop an expertise in epidemiological research methods, with a particular focus on infection risk in psoriasis patients treated with biologic therapies. The risk and predictors of: serious infections; skin and soft tissue infections and respiratory infections will be determined in patients on biologics as compared to conventional systemic therapies for psoriasis, with an emphasis on determining whether the risk involved is time-dependent. The differential individual biologic infection risk will also be determined in each of these categories. Based upon the significant baseline predictors of serious infection, an algorithm and infection risk prediction score will be produced and validated. The hypothesis is, when controlled for relevant predictors of infection, biologic therapies infer no greater infection risk to psoriasis patients as compared to conventional systemic therapies. The hypothesis for individual biologic infection risk is ustekinumab has a lower infection risk than the tumour necrosis factor antagonist therapies. Methods: Data accrued in the British Association of Dermatologists Biologic Interventions Register (BADBIR), a national prospective longitudinal pharmacovigilance register for biologics that includes a comparator cohort of patients on conventional systemic therapies, will be used. To date, over 9500 patients have been recruited to BADBIR. Parametric survival analysis will be used to model comparative risk and predictors of infections. The results will inform the wider medical and patient communities on the short and long-term biologic infection risk in psoriasis. It will assist clinicians in assessing infection risk and inform discussion with patients, enabling individual biologic therapy stratification based upon baseline demographic and comorbidity status. Serious infections may be circumvented by accurate baseline risk estimation and change in modifiable factors. This may potentially shift the current biologic prescribing paradigm in psoriasis.

Lay abstract: Psoriasis is a long-term, currently incurable, skin condition which can be life-ruining. New injectable treatments for psoriasis, called biologic therapies, work by blocking certain pathways in the immune system. Biologic therapies are very effective, giving control to many patients with severe psoriasis who have previously failed other therapies. Many patients and doctors, however, are concerned about the potential risk of infections, particularly life-threatening, whilst on a biologic therapy. Using a large national, well-established, long-term ongoing database of people with psoriasis on biologic therapies and other oral medications, I plan to test whether or not people on biologic therapies have a risk of infection over and above those on other oral medications for psoriasis. I plan to test whether any of the currently available biologic therapies have a higher risk than the other biologic therapies. I will test in particular the risk of developing serious infections, which are those that lead to hospital admission and require intravenous antibiotic treatment, or death; chest infections; and skin and soft tissue infections on biologic therapies. I will analyse whether there is any specific infection that is more common in patients on biologic therapies. With the estimates in serious infection risk produced from the above analysis, an infection risk prediction score will be produced in order to give patients a personalised risk estimation prior to the decision to start a particular biologic therapy. The objective of the study is to provide both psoriasis patients and their doctors with an accurate estimate of the risk of infection while on biologic therapies, and to identify any factors that could predict the occurrence of infection whilst on these drugs. Patients and doctors can thereby make well-informed decisions to choose a particular biologic treatment, take appropriate lifestyle modifications or direct timely monitoring of therapy to reduce the likelihood of serious infections whilst using biologic therapies.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: SKIN