Novel Biologics in Psoriasis—Safety Considerations

Publication
Article
Bridging the GapsNew Directions and Practice-Impacting Recommendations in Plaque Psoriasis

This publication was developed independently by MJH Life Sciences Global Medical Affairs. Support for the thought leaders meeting and the publication was provided by Arcutis Biotherapeutics, Inc; The Bristol Myers Squibb Company; Janssen Global Services, LLC; and UCB, Inc.

Some biologic therapieshave been linked to inflammatory bowel disease (IBD), malignancy, liver function test (LFT) abnormalities, and suicidal ideation and behavior. Before adding biologics to a patient’s treatment regimen, clinicians should consider an individual’s health history and discuss the risks and benefits of using these agents with the patient.1 The frequency and extent of laboratory monitoring advised to assess organ function in patients being treated with biologic thera­pies has decreased considerably in recent years with the advent of interleukin-17 (IL-17) and IL-23 inhibitors.

Inflammatory Bowel Disease

Patients with psoriasis (PsO) and psoriatic arthritis have a higher back­ground risk of developing IBD; the prevalence of IBD in this population is approximately 1.2%. Because inhibition of IL-17 may worsen disease activity in patients with Crohn disease, concerns have arisen about development of new-onset IBD with use of IL-17 inhibitors.2 Results from a systematic review and meta-analysis; a nationwide, popula­tion-based analysis of the French National Health Data System; and a retrospective cohort analysis of patients with PsO found that the risk of developing IBD was similar between users and nonusers of IL-17 inhibitors.2-4 However, an analysis of data obtained from 2015-2022 from the FDA’s Adverse Event Reporting System database found a considerably increased risk of IBD events with use of secukinumab and ixekizumab but not with brodalumab therapy.5

Practitioners should ask patients about a history of IBD symptoms (eg, bloody diarrhea) when discussing treatment options, because an IL-17 inhibitor may not be the preferred treatment for patients with a personal history of IBD.

Malignancy

Patients with PsO have an increased risk for lymphoma, keratino­cyte cutaneous squamous cell carcinoma, and some solid cancers.6 Cancer has also been listed as a serious adverse event (AE) related to use of biologic agents used to treat PsO.6 A systematic review and meta-analysis of observational cohort studies found that the risk of several cancers was elevated in patients with PsO, but treatment with biologic agents did not further increase this risk.6 An analysis of data from the Psoriasis Longitudinal Assessment Registry (PSOLAR; NCT00508547) found that cancer risk was not increased with use of ustekinumab or methotrexate over any time period, but tumor necrosis factor-α (TNFα) inhibitor treatment for 12 months or longer significantly increased the risk of lung cancer development in patients with PsO (odds ratio, 3.54; 95% CI, 1.15- 10.92; P = .028).7 However, the authors noted that the large CIs and small number of events presented a challenge as they interpreted the data.7 Distinguishing the actual contribution of biologic agents to cancer risk is difficult when PsO itself is associated with certain malignancies. Furthermore, biologic agents—including TNFα inhibi­tors—are extremely effective for long-term skin clearance in many patients. Changing therapies solely because of a potential increase in malignancy risk is generally not advised if the treatment continues to be effective.

Liver Function Abnormalities

Increases in serum transaminase levels were reported during phase 3/3b clinical trials of bimekizumab, an IL-17A and IL-17F inhibitor approved for the treatment of moderate to severe plaque PsO in adults.1,8 In a pooled analysis of patients in the phase 3 BE VIVID (NCT03370133), BE READY (NCT03410992), BE SURE (NCT03412747), and BE RADIANT (NCT03536884) trials over 1 year, hepatic treatment-emergent AEs (TEAEs) occurred in 4.0% of patients; however, the majority of cases were temporary and asymptomatic, and the rate of treatment discontinuation due to hepatic TEAEs or abnormal LFT results was extremely low (0.2%-0.5%). Serum transaminase levels with bimekizumab were comparable or lower than placebo or with active comparators (ustekinumab, adalimumab, and secukinumab). Further­more, the incidence of hepatic TEAEs with bimekizumab use appeared to be lower at year 2 than at year 1; hepatic TEAEs often resolved with continued treatment or soon after discontinuation of therapy. Patients with PsO often have comorbidities (eg, alcohol consumption, nonal­coholic fatty liver disease, hepatitis C infection) that can contribute to elevated serum transaminase levels; therefore, practitioners should perform laboratory monitoring at an appropriate frequency based upon the patient’s risk factors. An LFT measurement at baseline and 3 months after starting bimekizumab can be beneficial in identifying any abnormalities, and LFTs obtained every 6 months thereafter may be particularly beneficial for patients with chronic liver disease. However, LFTs performed annually may be adequate for some patients without identified liver function abnormalities.

Psychiatric Comorbidities

Depression and suicidality are known comorbidities of PsO. A system­atic review and meta-analysis found that suicidal ideation, suicide attempts, and completion of suicide occurred more frequently among patients with PsO.9 Additionally, a higher rate of suicidal ideation wasreported with bimekizumab use in the 16-week, placebo-controlled period of the BE READY and BE VIVID trials.1 In the open-label extension study, 1 completed suicide by a participant receiving bime­kizumab occurred after 2 years, and there were 3 attempted suicides among patients receiving bimekizumab and having a history of neuropsychiatric comorbidities.1

The prescribing information for bimekizumab states that prescribers should consider the risks and benefits before prescribing the drug for patients with a history of severe depression or suicidal ideation and behavior.1 However, the overall rate of suicidal ideation and behavior with bimekizumab across the clinical trial program was 0.13 per 100 patient-years, which falls within the reported background rates in patients with PsO (0.09-0.54 per 100 patient-years). Because depres­sion is such a common comorbidity that can be severe in patients with PsO, practitioners should address the patient’s overall mental and emotional health early in the treatment process regardless of the medication prescribed. A patient’s quality of life—and in turn, mental and emotional health—could also improve if bimekizumab (or another biologic) improves the patient’s skin appearance.

Similarly, a risk for suicidal ideation and completed suicide has been observed with brodalumab treatment. The brodalumab Risk Evalua­tion and Mitigation Strategy was developed as a safety program to ensure that the benefits received by this therapy outweigh its risks. The program educates patients and providers on suicide and when patients should seek help.

Take-Home Messages

In general, biologic therapies are safe to use in most patients with moderate to severe PsO. IL-17 and IL-23 inhibitors are preferred for use in patients with a history of malignancy, because their use has not been associated with an increased risk for cancers. Awareness of the potential risk for IBD with IL-17 inhibitors is important, although the risk of new-onset IBD with IL-17 inhibition is likely low. For LFT abnormalities associated with bimekizumab use, an adequate laboratory monitoring schedule may involve tests at baseline and then 3 months after starting bimekizumab and every 6 to 12 months thereafter depending on the patient’s liver health. Finally, a patient’s history of depression and suicidal ideation should be addressed early in the treatment process.

Faculty presenter: Jennifer Soung, MD. This article was reviewed, edited, and approved by Dr Soung and Dr Stein Gold.

References

  1. Bimzelx. Prescribing information. UCB. Updated October 2023. Accessed December 28, 2023. https://www.bimzelx.com/prescribing-information.pdf
  2. Burisch J, Eigner W, Schreiber S, et al. Risk for development of inflammatory bowel disease under inhibition of interleukin 17: a systematic review and meta-analysis. PLoS One. 2020;15(5):e0233781. doi:10.1371/journal.pone.0233781
  3. Penso L, Bergqvist C, Meyer A, et al. Risk of inflammatory bowel disease in patients with psoriasis and psoriatic arthritis/ankylosing spondylitis initiating interleukin-17 inhibitors: a nationwide population-based study using the French National Health Data System. Arthritis Rheumatol. 2022;74(2):244-252. doi:10.1002/art.41923
  4. Wright S, Alloo A, Strunk A, Garg A. Real-world risk of new-onset inflammatory bowel disease among patients with psoriasis exposed to interleukin 17 inhibitors. J Am Acad Dermatol. 2020;83(2):382-387. doi:10.1016/j.jaad.2020.04.010
  5. Deng Z, Wang S, Wu C, Wang C. IL-17 inhibitor-associated inflammatory bowel disease: a study based on literature and database analysis. Front Pharmacol. 2023;14:1124628. doi:10.3389/fphar.2023.1124628
  6. Vaengebjerg S, Skov L, Egeberg A, Loft ND. Prevalence, incidence, and risk of cancer in patients
    with psoriasis and psoriatic arthritis: a systematic review and meta-analysis. JAMA Dermatol. 2020;156(4):421-429. doi:10.1001/jamadermatol.2020.0024
  7. Fiorentino D, Ho V, Lebwohl MG, et al. Risk of malignancy with systemic psoriasis treatment in the
    Psoriasis Longitudinal Assessment Registry. J Am Acad Dermatol. 2017;77(5):845-854.e5. doi:10.1016/j.jaad.2017.07.013
  8. UCB announces US availability of Bimzelx for the treatment of adults with moderate-to-severe plaque
    psoriasis. Press release. PR Newswire. November 14, 2023. Accessed December 28, 2023. https://
    www.prnewswire.com/news-releases/ucb-announces-us-availability-of-bimzelx-for-the-treatment-ofadults-
    with-moderate-to-severe-plaque-psoriasis-301986731.html.
  9. Singh S, Taylor C, Kornmehl H, Armstrong AW. Psoriasis and suicidality: a systematic review and metaanalysis.
    J Am Acad Dermatol. 2017;77(3):425-440.e2. doi:10.1016/j.jaad.2017.05.019
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