Case study: Long term safety of psoriasis treatments
BADBIR: Biologics and Immunomodulators Register
BADBIR: Biologics and Immunomodulators Register
Psoriasis is a common, currently incurable, lifelong skin disease. In addition to affecting the skin, psoriasis is also associated with an increased risk of depression, arthritis, cardiovascular disease, chronic kidney disease and reduced life span.
Psoriasis most commonly develops in adults under the age of 35 and affects nearly two million people in the UK - costing the NHS in the region of £1.5 billion per annum. Patients often require lifelong treatment to manage their disease, which may expose them to toxic and potentially fatal side effects.
Biologics are one type of psoriasis treatment, licensed for use on the NHS. They are commonly used to treat severe psoriasis, especially among those where other treatments have failed or are contraindicated. Prior to BADBIR, the main clinical evidence around biologics had been established through relatively short randomised controlled trials, powered to detect differences in efficacy rather than side effects related to long term use in the real world. Consequently, long term effects and risks of biologics were not well understood.
BADBIR set out to address these gaps in evidence by monitoring the long term safety of biologics - while comparing safety and efficacy with conventional oral systemic treatments such as methotrexate. Commissioned by the British Association of Dermatologists (BAD), patient enrolment began in 2007 and the study is currently ongoing - with ethical approval to continue until 2028.
The longitudinal, observational study uses a unique web-based register to record data from three psoriasis patient cohorts. The first cohort is made up of patients treated with biologics; the second cohort consists of patients with similar disease characteristics receiving standard anti-psoriatic systemic treatments; while a third, new cohort, is made up of patients receiving the new small molecule therapies.
Patients in all three cohorts are followed up by their dermatologist. Clinicians record changes in therapy, disease activity and adverse events every six months for the first three years, and then annually for as long as the patient remains in the register. The register is actively monitored by the steering committee chaired by Professor David Burden (Glasgow) and analysed by the BADBIR research team chaired by Professor Nick Reynolds (Newcastle). The operational team for BADBIR is situated in Manchester and currently comprises 12 staff. A designated pharmacovigilance physician and chief investigator reviews all serious adverse event data and shares these with the relevant drug manufacturer and with the Data Management Committee, chaired by Professor Carsten Flohr (London).
Relevant health data are shared with NHS Digital and equivalent agencies in devolved nations to capture occurrence of malignancy or death related to use of biologics.
BADBIR was adopted on to the NIHR Clinical Research Network (CRN) Portfolio in 2010 - allowing investigators to access NIHR CRN infrastructure. The additional administrative and research nurse support provided a major catalyst around recruitment and promotion of the study through the NIHR CRN Dermatology Specialty Group.
With support from the BAD, the National Institute for Health and Care Excellence (NICE), and the NIHR CRN - 160 Dermatology Centres in the UK and Eire have recruited to BADBIR, with 17,000 patient registrations to date. It is now the largest and most comprehensive pharmacovigilance register in the world.
- BADBIR is a web-based database/register of psoriasis patient data
- Chief investigator: Professor Christopher Griffiths, University of Manchester
- Participants:17,000 registrants across the UK and Ireland
- Sites: Delivered through over 160 dermatology centres across the UK and Ireland
- Enrollment began in 2007 and is ongoing
Although the study is currently ongoing, there have already been many publications from BADBIR - with vital evidence reported around the safety and efficacy of biologic therapies, enabling improved clinical decision making. Some of the key findings are highlighted here:
Improvement in quality of life
The study has shown that in routine clinical practice, biologic therapies produce marked improvements in health related quality of life (HRQoL) - influenced by the choice of therapy, lifestyle characteristics and comorbidities. These findings should help inform the selection of optimal biologic therapies for patients.
Risk of serious infection
BADBIR has found no significant increases in the risk of serious infection for the biologic drugs assessed (etanercept, adalimumab, and ustekinuma) compared with non-biologic systemic therapies - although there is an increased risk of serious infection with infliximab.
Drug survival measures the length of time until discontinuation of a drug - reflecting its effectiveness, safety and tolerability. Of the drugs assessed, patients on ustekinumab were more likely to persist with treatment, while patients on etanercept or infliximab were more likely to discontinue therapy.
“Psoriasis is a common, currently incurable skin disease that produces significant physical, psychological and societal detriment. The introduction of biologic therapies for psoriasis has been truly life-transforming for many patients with severe forms of the disease. The efficacy and safety profile of biologic therapies in clinical trials has been impressive - however it is important to ascertain whether this is the case over the long-term in real-world clinical practice.
“The role of BADBIR (acknowledged as the world-leading independent psoriasis pharmacovigilance register) is to provide the number of patients and years of follow-up to allow us to address these concerns. We are now at this stage and to date the benefit to risk ratio of these powerful treatments appears to be very good.”
Professor Christopher Griffiths, Chief Investigator of BADBIR
Value to the NHS
BADBIR’s potential to improve care and treatment for psoriasis patients through improving clinical knowledge around the safety and effectiveness of psoriasis therapies is significant. The study is not only providing vital data on the safety of biologic treatments (such as risk of serious infection and cancer), but also helping to identify predictors of response to a biologic therapy aligned with BADBIR’s sample resource of 6,000 patients who provided DNA and/or blood serum samples.
“In comparing the safety and efficacy of these new biologic treatments with conventional systemic oral medications, BADBIR is opening an era of personalised medicine - which is helping to change the lives of people with severe cases of psoriasis.
“Since biologic treatments were approved by NICE, they have changed the lives for thousands of people who cannot take conventional systemic drugs. These people often spent 6-8 weeks per year in hospital having messy, sore and smelly treatments. Now they can have a quick injection at home every few weeks or few months to be clear.”
Professor Nick Levell, NIHR CRN National Specialty Lead for Dermatology
- Study site: www.badbir.org/Publications