Ipilimumab and serous retinal detachment

Treatment with ipilimumab has been linked to the rare yet serious adverse event of serous retinal detachment. The amount of photoreceptor degeneration and loss of vision can be minimised by early diagnosis and treatment.

Ipilimumab is a human monoclonal antibody that binds to the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and boosts the response of the immune system to cancer cells. It is marketed in Australia as Yervoy.

Ipilimumab is indicated as monotherapy for the treatment of patients with melanoma; in combination with nivolumab for the treatment of melanoma, renal cell carcinoma and malignant pleural mesothelioma; and in combination with nivolumab and 2 cycles of platinum doublet chemotherapy for the treatment of non-small cell lung cancer.

As ipilimumab upregulates the immune system, autoimmune-like side effects may result in ocular changes that include serous retinal detachment. Visual acuity may decrease when the macula becomes detached, and consequently the patient may notice a distortion of images. Without prompt treatment, total retinal detachment and blindness may occur.

Warnings about serous retinal detachment and transient vision loss have been incorporated in Section 4.4 of the PI for ipilimumab as follows (new text underlined):

• 'In the post-marketing setting, cases of Vogt-Koyanagi-Harada syndrome and serous retinal detachment have been reported (see Section 4.8 Adverse effects).

  For ipilimumab-related uveitis, iritis, serous retinal detachment or episcleritis, topical corticosteroid eye drops should be considered as medically indicated. Transient vision loss has been reported in patients with ipilimumab-related ocular inflammations.

  Other clinically significant immune-related adverse reactions, including some with fatal outcome, have been observed across clinical trials of ipilimumab in combination with nivolumab investigating various doses across tumour types (see Section 4.8 Adverse effects). These include rare cases of myotoxicity. Cases of Vogt-Koyanagi-Harada syndrome and serous retinal detachment have been reported post-marketing (see Section 4.8 Adverse effects). Transient vision loss has been reported in patients with ipilimumab-related ocular inflammations. Refer to the Product information for nivolumab.'

The following has been added to Section 4.8 of the PI in Post-marketing experience:

• 'Eye disorders: Serous retinal detachment'.

Information for health professionals

No cases of retinal detachment have been reported post-marketing in Australia.

The decision to add these warnings was based on evidence published in the literature and the seriousness of the adverse reaction.^[1-3]

It is important for physicians, ophthalmologists and patients to be aware of this possible adverse reaction because without appropriate treatment, many retinal detachments progress to involve the central retina and may lead to loss of vision.

What to report? You don't need to be certain, just suspicious!

The TGA encourages the reporting of all suspected adverse reactions to medicines, including vaccines, over-the-counter medicines, herbal, traditional or alternative remedies.

We particularly request reports of:

• all suspected reactions to new medicines (look for the Black Triangle in PI and CMI documents - this symbol identifies medicines that are new or being used differently)
• all suspected medicines interactions
• suspected reactions causing death, admission to hospital or prolongation of hospitalisation, increased investigations or treatment, or birth defects.

Reports may be submitted:

• online at www.tga.gov.au
• by fax to 02 6232 8392
• by email to ADR.Reports@tga.gov.au

For more information about reporting, visit www.tga.gov.au or contact the TGA's Pharmacovigilance and Special Access Branch ADR.Reports@tga.gov.au.

Disclaimer

Medicines Safety Update is aimed at health professionals. It is intended to provide practical information to health professionals on medicine safety, including emerging safety issues. The information in Medicines Safety Update is necessarily general and is not intended to be a substitute for a health professional's judgment in each case, taking into account the individual circumstances of their patients. Reasonable care has been taken to ensure that the information is accurate and complete at the time of publication. The Australian Government gives no warranty that the information in this document is accurate or complete, and shall not be liable for any loss whatsoever due to negligence or otherwise arising from the use of or reliance on this document.

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Medicines Safety Update is written by staff from the Pharmacovigilance and Special Access Branch.

Acting Editor: Dr Catherine Brogan

Deputy Editor: Mr Michael Pittman

Contributor: Ms Tara Banks, Ms Renae Mura