Infliximab to Improve Retention of the Boston Keratoprosthesis in Patients After Stevens Johnson Syndrome/ Toxic Epidermal Necrolysis (SJS/TENS)

The closely related disorders, Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis
Syndrome (TENS), represent rare but severe hypersensitivity responses to a systemic
medication, and cause severe sloughing of the skin and mucous membranes. Approximately half
of affected patients experience ocular involvement, which can lead to corneal opacity and
vascularization, and in some patients, blindness. Corneal transplantation (corneal
allograft) is typically unsuccessful in SJS/TENS, because of chronic inflammation at the
ocular surface, leading to corneal neovascularization and opacity, tissue melt, ulceration,
and perforation.

The Boston keratoprosthesis, an artificial cornea developed at the Massachusetts Eye and Ear
Infirmary (MEEI) over the last 40 years, is an FDA approved device for patients with corneal
blindness not amenable to corneal transplantation, and has restored the sight of thousands
of such patients, but in SJS/TENS patients remains associated with tissue melts (tissue
ulceration), perforation, and ultimately in some, loss of the eye. K-Pro surgery is
currently the best option for patients with SJS or TENS and corneal blindness, but these
patients also have the worst prognosis after surgery. While the outcomes of these surgeries
for patients with SJS or TENS have improved dramatically in the past ten years, they are
still unsatisfactory. Remicade® has been used in a small group of patients with SJS or TENS
undergoing K-Pro surgery, with one remarkable success. The purpose of this study is to
explore this treatment more fully.

For a case report detailing the use of infliximab in one patient, see the following article:
Dohlman JG, Foster CS, Dohlman CH. "Boston Keratoprosthesis in Stevens-Johnson Syndrome: A
case of using infliximab to prevent tissue necrosis." Digital Journal of Ophthalmology.
2009, Volume 15, Number 1.

Recently developed biologics have dramatically improved functional outcomes and quality of
life in patients with autoimmune diseases. One such agent, infliximab, acts by blocking TNF
alpha, a protein associated with tissue melting in the cornea, and is increasingly being
used for autoimmune eye conditions, in addition to its FDA approved indication for
recalcitrant rheumatoid arthritis.

The proposed study will determine the feasibility of combining infliximab with
keratoprosthesis surgery, and will closely monitor patients for episodes of corneal melting:
the primary outcome of the study.

Inclusion Criteria:

- History of biopsy proven SJS/TENS with corneal opacity and neovascularization

- Bilateral legal blindness (<20/200 in better eye)

- 18 years of age or older

- Able to provide informed consent

- Sufficiently healthy to undergo infliximab infusions, surgery, and a vigorous
postoperative follow-up course

- Able to administer eye medications or have a care giver able and willing to do same

- Are considered eligible according to the following tuberculosis (TB) screening
criteria:

- Have no history of latent or active TB prior to screening.

- Have no signs or symptoms suggestive of active TB upon medical history and/or
physical examination.

- Have had no recent close contact with a person with active TB.

- Within 6 weeks prior to the first administration of study agent, have a negative
QuantiFERON-TB Gold test result (see Attachment A). Indeterminate results should
be handled as outlined in the Screening Visit Section. A negative tuberculin
skin test is considered acceptable if the QuantiFERON- TB Gold test is not
acceptable in that country.

- Have a chest radiograph (posterior-anterior view) taken within 3 months prior to
the first administration of study agent and read by a qualified radiologist,
with no evidence of current, active TB or old, inactive TB.

Exclusion Criteria:

- Visual acuity >20/200 in better eye

- Corneal blindness not due to effects of SJS/TENS

- Hypersensitivity to infliximab or chemically related medication

- Pregnant or lactating

- Have a history of latent or active granulomatous infection, including histoplasmosis
or coccidioidomycosis, prior to screening. Refer to inclusion criteria for
information regarding eligibility with a history of latent TB.

- Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening.

- Have a chest radiograph within 3 months prior to the first administration of study
agent that shows an abnormality suggestive of a malignancy or current active
infection, including TB.

- Have had a nontuberculous mycobacterial infection or opportunistic infection (eg,
cytomegalovirus, pneumocystosis, aspergillosis) within 6 months prior to screening.

- Have indeterminate initial and repeat QuantiFERON-TB Gold test results.

- History or current diagnosis of diabetes mellitus

- History of immune system problem other than Stevens Johnson Syndrome

- History of recurrent infections

- History or current diagnosis of cancer

- Active psoriasis

- History of heart failure

- History of hepatitis B virus

- MRSA or VRE infection

- Nervous system disorders such as multiple sclerosis or Guillain-Barre syndrome

- Scheduled to receive a live vaccine at any time point during study participation

- Currently receiving treatments of Kineret (Anakinra)

- Unable to attend postoperative visits or administer medications, or no care giver
available and willing to assist with same