Biologics are an effective

Novel therapy for severe disease

Biologics effective fall-back option in severe corneal disease. Dermot McGrath reports

Biologics are an effective therapeutic option worth considering in cases of severe corneal and external eye diseases refractory to systemic steroids and conventional immunosuppressive drugs, according to Omar Elhaddad MB BCh, MSc, MRCS (Ophth), FRCOphth.

“In our experience biologic agents show a very early response to disease activity, usually within two weeks, and particularly with infliximab. They are effective in treating severe cases such as peripheral ulcerative keratitis (PUK) and mucous membrane pemphigoid (MMP) that failed to respond to more conventional treatments such as prednisolone or mycophenolate mofetil,” he said.

Biologic drugs include a wide variety of products derived from human, animal, or microorganisms and are usually administered as a drip infusion or an injection, said Dr Elhaddad. He noted that two broad categories of biologics are used at the Bristol Eye Hospital – anti-TNF alpha agents such as infliximab and adalimumab and non-antiTNF drugs such as rituximab.

Dr Elhaddad presented a selection of case studies to illustrate the utility of biologics in a real-world clinical setting. The first example was two patients, both in their 60s, who presented with no symptoms apart from bilateral corneal thinning and extensive inflammation.

Both had been on long-term oral steroids for at least three months before referral. They were administered prednisolone and mycophenolate mofetil, but showed no improvement over four to six weeks. Methotrexate was also tried in one patient without any positive impact. After they were switched to infliximab, both patients showed rapid improvement, with complete control of disease activity and conjunctivalisation of the ulcerated cornea after two to three weeks.

The second clinical scenario presented by Dr Elhaddad concerned a patient who presented with ocular manifestations of mucous membrane pemphigoid, including fibrosis, limbitis, and diffuse conjunctival hyperaemia in all four quadrants. Again, various drugs such as prednisolone, mycophenolate mofetil and cyclophosphamide were ineffective. He was then treated with a rituximab infusion which resolved the limbitis and calmed the inflammation.

Before starting patients on biologics, it is important to screen patients for malignancies and infectious diseases such as tuberculosis, as well as hepatitis B and C, said Dr Elhaddad.

In terms of outcomes, Dr Elhaddad said that all patients treated at Bristol Eye Hospital showed a very early response. Patients were switched to different anti-TNF agents in about 67% of cases and standard immunosuppression drugs were also continued for all patients while on biologics. All patients achieved good preservation of visual acuity. There was one death of unknown cause of a patient on rituximab.

Dr Elhaddad added that the experience of the clinic in Bristol Eye Hospital accorded with the limited studies in the scientific literature concerning the use of biologics in severe cases of corneal disease.