Belimumab (Benlysta▼): increased risk of serious psychiatric events seen in clinical trials

Clinical trials, including interim findings from a randomised trial, show an increased risk of depression, suicidal ideation or behaviour, or self-injury in patients with systemic lupus erythematosus receiving belimumab compared with those receiving placebo in addition to standard therapy. Assess patients for these risks before the start of treatment with belimumab and advise them to promptly seek medical attention if they develop new or worsening depression, suicidal ideation or thoughts about injuring themselves.

• From: Medicines and Healthcare products Regulatory Agency
• Published: 16 April 2019

• Therapeutic area: Dermatology, Psychiatry, Rheumatology, Urology and nephrology

Advice for healthcare professionals:

• an increased risk for serious psychiatric events (depression, suicidal ideation or behaviour [including death by suicide], or self-injury) has been observed in patients receiving belimumab from clinical trials, including recent interim findings from a randomised trial

• carefully assess the risk of depression and suicide, considering the patient’s medical history and current psychiatric status, before belimumab is started

• monitor all patients for new or worsening signs of these risks during treatment

• in patients with new psychiatric symptoms or if existing psychiatric symptoms worsen, assess the benefits and risks of continuing treatment
• report any suspected adverse reactions, including alterations of mood, associated with belimumab to the Yellow Card Scheme

Advice to give to patients (and caregivers if appropriate):

• people taking belimumab may experience changes in their mood or behaviour, and should promptly seek medical attention if they experience new or worsening depression, suicidal ideation, or thoughts about injuring themselves
• patients may wish to let family and friends know they are taking belimumab so they can look out for any changes in mood

Risk of suicidal thoughts and behaviour

An imbalance in rates of psychiatric events was observed in the clinical studies that led to the approval of belimumab. Assessment found the benefits of belimumab to outweigh the risks. However, as a condition of its licence, the marketing authorisation holder for belimumab was requested by regulators to conduct a randomised, placebo-controlled clinical trial (BEL115467) to evaluate all-cause mortality and pre-specified adverse events of special interest, including selected serious psychiatric events. The study is global and currently ongoing.

1-year data from this study show that, compared with patients who received placebo plus standard therapy, more patients who received belimumab plus standard therapy reported events of serious depression and suicidal ideation or behaviour or self-injury (see table).

Prescribers are therefore advised to carefully assess the risk of depression and suicide, considering the patient’s medical history and current psychiatric status, before belimumab is started and to advise patients to seek medical attention if they experience new or worsening psychiatric symptoms.

Table: Patients reporting serious depression or suicidality (as-treated population, study BEL115467)

• Group: Number of patients reporting serious depression (as per study investigator report)
  • Placebo (N=2001): 1 (<0.1%)
  • Belimumab IV 10 mg/kg (N=2002): 7 (0.3%)
• Group: Number of patients reporting suicidal ideation or behaviour or self-injury* (as per study investigator report)
  • Placebo (N=2001): 5 (0.2%)
  • Belimumab IV 10 mg/kg (N=2002): 15 (0.7%)

About belimumab

Belimumab is a human IgG1λ monoclonal antibody, specific for soluble human B-lymphocyte stimulator protein. Belimumab is authorised for the treatment, as add-on therapy, of adults with active, autoantibody-positive systemic lupus erythematosus with a high degree of disease activity (for example, positive anti-dsDNA and low complement) despite standard therapy. In 2018 the UK estimated exposure to belimumab was 102 patient-years. ^{[footnote 1]}

Report suspected adverse drug reactions via the Yellow Card scheme

As for all medicines, MHRA will continue to monitor the benefit and risks of belimumab. Please continue to report any suspected adverse drug reaction via the Yellow Card Scheme. Remember only a suspicion is needed to report – if in doubt, please complete a Yellow Card.

Healthcare professionals, patients, and caregivers can report suspected side effects via the Yellow Card website or via the Yellow Card app. Download the app today via iTunes Yellow Card for iOS devices or via PlayStore Yellow Card for Android devices.

You can also use the app to access the latest safety information from the MHRA about medicines and medical devices on the Newsfeed. Search for medicines to see details of Yellow Card reports others have made. Medicines of interest can also be added to a Watch List to receive news and alerts about new side effects and safety advice as it emerges.

Further information

Letter to healthcare professionals, March 2019.

Article citation: Drug Safety Update volume 12, issue 9: April 2019: 3.

1. Data derived by MHRA, in March 2019, from IQVIA MIDAS 2018. Patient-years estimated by using defined daily doses (DDD) as provided by WHO. ↩

Published 16 April 2019