NIHR Signal Biological therapies for psoriasis do not increase serious infection risk

Published on 23 January 2018

People with psoriasis who take an immune-modulating treatment are no more likely to get serious infections than people taking standard therapies.

There are fears that these biological therapies raise the risk of serious infections and this has discouraged their use. They are recommended by NICE for moderate to severe psoriasis. Previous studies have reached conflicting conclusions, making it hard to advise on the true risk.

This study used a large database of people with psoriasis from the UK and Ireland. It compared serious infection risk of the biological therapies (etanercept, adalimumab or ustekinumab) with non-biological therapies, after accounting for factors such as other illnesses. It found none of the biological therapies studied had a higher risk of infection compared to non-biological therapies or compared to each other.

The results should encourage adherence to the recent British Association of Dermatology guideline on the use of biologic therapies in psoriasis.

Biological therapies for psoriasis do not increase serious infection risk

Share your views on the research.

Why was this study needed?

Psoriasis is an immune disease of the skin condition affecting 1 to 2% of the UK population, with 60% requiring specialist treatment at some point. Treatment is targeted at reducing inflammation by suppressing the body’s immune responses. Milder local disease can be managed with creams, but people often need oral treatment, initially non-biological but often biological therapies, which are prescribed and monitored by specialists.

It is not clear whether serious infections are more common with biological therapies than non-biological immunosuppressant oral treatments, such as methotrexate. Tuberculosis can remain dormant but may reactivate when the body’s immune system is suppressed.

Previous studies have been inconclusive and conflicting, partly because they have varied in which drugs they included in their analysis, size of the study, and whether they were able to account for potential confounding factors. This study aimed to find out whether the NICE-approved drugs etanercept, adalimumab and ustekinumab are more likely to lead to serious infection than other oral treatments for psoriasis.

What did this study do?

Researchers used data from a large, national registry of people with psoriasis - the British Association of Dermatologists Biological Interventions Register - to carry out a prospective cohort study.

They compared serious infection rates for 3,421 people taking non-biological oral therapies, and 5,617 people taking etanercept, adalimumab or ustekinumab. They excluded the biological therapy secukinumab because few people had used it, and infliximab because the prescribing criteria mean it is used by people with more severe disease. They looked at infection rates and the type of infection.

They adjusted their results to account for potentially confounding factors, such as disease severity, other illnesses, other immunosuppressant drugs and immunodeficiency syndromes. This was a well-conducted cohort study.

What did it find?

  • None of the biological therapies had a statistically significant increased risk of serious infection, compared to non-biological oral therapies (hazard ratio for all biological therapies combined 0.96, 95% confidence interval [CI] 0.73 to 1.27). No biological therapy had a higher risk of infection than another biological therapy, after accounting for confounding factors.
  • The rate of serious infections per 1000 people per year was 14.18 (95% CI 11.54 to 17.41) for non-biological therapies, 15.25 for etanercept (95% CI 11.56 to 20.11), 13.78 for adalimumab (95% CI 11.41 to 16.64) and 15.07 for ustekinumab (95% CI 10.77 to 21.09).
  • Types of serious infections were similar between biological and non-biological therapies. The most commonly reported were lower respiratory tract infections, followed by skin and soft tissue infections and urinary tract infections. No patients taking adalimumab or ustekinumab died within 30 days of the infection, compared to fewer than five taking etanercept and seven taking non-biological therapies. 

What does current guidance say on this issue?

NICE 2017 guidance recommends use of certain biological therapies, including etanercept, adalimumab and ustekinumab, for moderate to severe psoriasis, when standard oral therapy has not worked or cannot be used.

British Association of Dermatologists 2017 guidance recommends adalimumab, ustekinumab and secukinumab as first-line biological therapies, with etanercept as a second-line choice, because clinical trials have shown it to be less effective. 

What are the implications?

The risk of serious infection should not be a deciding factor between biological and non-biological oral treatments for psoriasis. Neither should it influence which biological therapy to choose as none was shown to have a different risk from the others.

The findings back the rationale for the British Association of Dermatologists’ guidelines on use of biological therapies in psoriasis, which suggest that treatment should be tailored to the individual, but that adalimumab, ustekinumab and secukinumab should be considered first-line.

There were low rates of tuberculosis in this UK based study and so results may not apply to populations with greater lifetime exposure to tuberculosis.

Citation and Funding

Yiu ZZN, Smith CH, Ashcroft DM, et al; BADBIR Study Group. Risk of Serious Infection in Patients with Psoriasis on Biologic Therapies: a Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR). J Invest Dermatol. 2017. [Epub ahead of print].

The research was supported by the NIHR Manchester and the Guy’s and St Thomas’ Biomedical Research Centres, and also had funding from the British Association of Dermatologists and the University of Manchester. One researcher was supported by an NIHR grant and other by Medical Research Council grants. 

Bibliography

NICE. Psoriasis: assessment and management. CG153. London: National Institute for Health and Care Excellence; 2017.

Smith CH, Jabbar-Lopez ZK, Yiu ZZ, et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017. Br J Dermatol. 2017;177(3):628-36.

Why was this study needed?

Psoriasis is an immune disease of the skin condition affecting 1 to 2% of the UK population, with 60% requiring specialist treatment at some point. Treatment is targeted at reducing inflammation by suppressing the body’s immune responses. Milder local disease can be managed with creams, but people often need oral treatment, initially non-biological but often biological therapies, which are prescribed and monitored by specialists.

It is not clear whether serious infections are more common with biological therapies than non-biological immunosuppressant oral treatments, such as methotrexate. Tuberculosis can remain dormant but may reactivate when the body’s immune system is suppressed.

Previous studies have been inconclusive and conflicting, partly because they have varied in which drugs they included in their analysis, size of the study, and whether they were able to account for potential confounding factors. This study aimed to find out whether the NICE-approved drugs etanercept, adalimumab and ustekinumab are more likely to lead to serious infection than other oral treatments for psoriasis.

What did this study do?

Researchers used data from a large, national registry of people with psoriasis - the British Association of Dermatologists Biological Interventions Register - to carry out a prospective cohort study.

They compared serious infection rates for 3,421 people taking non-biological oral therapies, and 5,617 people taking etanercept, adalimumab or ustekinumab. They excluded the biological therapy secukinumab because few people had used it, and infliximab because the prescribing criteria mean it is used by people with more severe disease. They looked at infection rates and the type of infection.

They adjusted their results to account for potentially confounding factors, such as disease severity, other illnesses, other immunosuppressant drugs and immunodeficiency syndromes. This was a well-conducted cohort study.

What did it find?

  • None of the biological therapies had a statistically significant increased risk of serious infection, compared to non-biological oral therapies (hazard ratio for all biological therapies combined 0.96, 95% confidence interval [CI] 0.73 to 1.27). No biological therapy had a higher risk of infection than another biological therapy, after accounting for confounding factors.
  • The rate of serious infections per 1000 people per year was 14.18 (95% CI 11.54 to 17.41) for non-biological therapies, 15.25 for etanercept (95% CI 11.56 to 20.11), 13.78 for adalimumab (95% CI 11.41 to 16.64) and 15.07 for ustekinumab (95% CI 10.77 to 21.09).
  • Types of serious infections were similar between biological and non-biological therapies. The most commonly reported were lower respiratory tract infections, followed by skin and soft tissue infections and urinary tract infections. No patients taking adalimumab or ustekinumab died within 30 days of the infection, compared to fewer than five taking etanercept and seven taking non-biological therapies. 

What does current guidance say on this issue?

NICE 2017 guidance recommends use of certain biological therapies, including etanercept, adalimumab and ustekinumab, for moderate to severe psoriasis, when standard oral therapy has not worked or cannot be used.

British Association of Dermatologists 2017 guidance recommends adalimumab, ustekinumab and secukinumab as first-line biological therapies, with etanercept as a second-line choice, because clinical trials have shown it to be less effective. 

What are the implications?

The risk of serious infection should not be a deciding factor between biological and non-biological oral treatments for psoriasis. Neither should it influence which biological therapy to choose as none was shown to have a different risk from the others.

The findings back the rationale for the British Association of Dermatologists’ guidelines on use of biological therapies in psoriasis, which suggest that treatment should be tailored to the individual, but that adalimumab, ustekinumab and secukinumab should be considered first-line.

There were low rates of tuberculosis in this UK based study and so results may not apply to populations with greater lifetime exposure to tuberculosis.

Citation and Funding

Yiu ZZN, Smith CH, Ashcroft DM, et al; BADBIR Study Group. Risk of Serious Infection in Patients with Psoriasis on Biologic Therapies: a Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR). J Invest Dermatol. 2017. [Epub ahead of print].

The research was supported by the NIHR Manchester and the Guy’s and St Thomas’ Biomedical Research Centres, and also had funding from the British Association of Dermatologists and the University of Manchester. One researcher was supported by an NIHR grant and other by Medical Research Council grants. 

Bibliography

NICE. Psoriasis: assessment and management. CG153. London: National Institute for Health and Care Excellence; 2017.

Smith CH, Jabbar-Lopez ZK, Yiu ZZ, et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017. Br J Dermatol. 2017;177(3):628-36.

Risk of Serious Infection in Patients with Psoriasis on Biologic Therapies: a Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR)

Published on 17 October 2017

Z Yiu, C Smith, D Ashcroft, M Lunt, S Walton, R Murphy, N Reynolds, A Ormerod, C. Griffiths, R Warren, BADBIR Study Group

Journal of Investigative Dermatology , 2017

Serious infection is a concern for patients with psoriasis on biologic therapies. We assessed the risk of serious infections of biologics used to treat psoriasis by comparison with a cohort on non-biologic systemic therapies in a propensity-score weighted Cox proportional hazards model using data from the British Association of Dermatologists Biologic Interventions Register (BADBIR). 1352, 3271 and 994 participants were included in the etanercept, adalimumab, ustekinumab cohorts respectively and 3421 participants in the non-biologic cohort. 283 patients had a serious infection; the incidence rates with 95% confidence interval (CI) /1000 person-years were: non-biologic 14.2 (11.5 to 17.4); etanercept 15.3 (11.6 to 20.1); adalimumab 13.9 (11.4 to 16.6); ustekinumab 15.1 (10.8 to 21.1). No significant increases in the risk of serious infection were observed for etanercept (hazard ratio (HR) 1.10 [95% CI 0.75 to 1.60]); adalimumab (HR 0.93 [0.69 to 1.26]) or ustekinumab (HR 0.92 [0.60 to 1.41]) compared against non-biologic systemic therapies or methotrexate only (etanercept HR 1.47 [0.95 to 2.28]; adalimumab HR 1.26 [0.86,1.84]; ustekinumab HR 1.22 [0.75,1.99]). The risk of serious infection should not be a key discriminator for patients and clinicians when choosing between non-biologic systemic therapies, etanercept, adalimumab and ustekinumab for the treatment of psoriasis.

Expert commentary

Ever since their introduction, I have always harboured a concern that treating psoriasis with biologics is associated with an increased risk of serious infection - when compared with the non-biologic treatments that I have been using for 30+ years.

This new data from the British Association of Dermatologists Biologic Interventions Register goes a long way to setting my mind at ease.

Although some of the confidence intervals are still quite wide, despite the large numbers of included participants, there is no obvious signal of additional concern for serious infection with the biologics assessed in this study.

Hywel C. Williams, NIHR Senior Investigator Emeritus; Director of the NIHR Health Technology Assessment Programme; Professor of Dermato-Epidemiology; Co-Director of the Centre of Evidence-Based Dermatology