Tofacitinib for Inflammatory Eye Disease

Phase 2

Conditions: Uveitis
Scleritis

Interventions: Drug: tofacitinib

Registration Number: NCT03580343

Lead Sponsor: Washington University School of Medicine

Brief Summary: Non-infectious inflammatory eye disease, such as uveitis and scleritis, is a chronic, auto-immune process that leads to vision loss. While steroids are effective in the short term, the side-effect profile of chronic steroid use necessitates the identification of effective steroid-sparing therapies. Tofacitinib is a small molecule that inhibits the signaling pathways of multiple inflammatory cytokines. The investigators plan to evaluate whether tofacitinib may have efficacy for patients with uveitis and / or scleritis.

Detailed Description: This study is a prospective, single-site, open-label investigation of tofacitinib for refractory uveitis. The study will be for 24 weeks, with potential 1-year extension for treatment responders. The patients will self-administer the medication.

Eligible patients would be those patients with a diagnosis of uveitis who meet the following criteria:

1. Disease sufficiently severe to require treatment with systemic corticosteroids, and

2. Referred from Ophthalmology to Rheumatology or Uveitis specialist for a steroid-sparing agent

For patients naive to oral steroid-sparing therapy (e.g., methotrexate, azathioprine, or mycophenolate), tofacitinib will be initiated as monotherapy. For patients who have failed or had only a partial response to oral steroid-sparing therapy, tofacitinib will be initiated as an add-on therapy. For patients intolerant to a conventional agent, tofacitinib will be initiated as replacement monotherapy. For patients who have failed biologic therapy (e.g. adalimumab), biologic therapy will be discontinued and tofacitinib will be initiated as replacement therapy without change to concurrent conventional steroid-sparing agents. Study visits will occur at baseline/enrollment, and weeks 4, 8, 12, 16, \& 24 (+/- 2 weeks). Clinic visits may occur more frequently as determined by the treating physician. Laboratory monitoring (Table 1) will be obtained according to standard of care for drug toxicity monitoring. Clinical responses will be evaluated at 24 weeks, with the primary outcome defined as treatment failure.

All patients will undergo a predetermined oral steroid taper starting at 60mg of prednisone (or equivalent) and tapering over 14 weeks (Table 2). All patients will undergo a predetermined topical steroid drop taper starting at their current dose (Table 3).

Patients will have an ophthalmological evaluation by their treating ophthalmologist at Washington University. Steroid sparing therapy will be managed by rheumatologists or uveitis specialists at Washington University. All patients will be evaluated for an associated systemic rheumatologic condition.

Recruitment & Eligibility

Status: UNKNOWN

Sex: All

Target Recruitment: 5

Inclusion Criteria

diagnosis of uveitis
a clinical response to steroids
active disease requiring at least 10mg of prednisone daily (or steroid equivalent)

Exclusion Criteria

suspected or confirmed ocular infection
chronic or recurring infections, such as HIV
renal insufficiency that would preclude safe administration of tofacitinib

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tofacitinib Treatment	tofacitinib	11mg extended-release tofacitinib, once daily, oral

Primary Outcome Measures

Name	Time	Method
Treatment Failure (Composite Outcome)	180 days	new inflammatory lesions relative to baseline OR 2-step increase in anterior chamber cell or vitreous haze OR worsening of visual acuity by two or more rows on ETDRS chart

Secondary Outcome Measures