Tofacitinib for Inflammatory Eye Disease

Tofacitinib for the Treatment of Inflammatory Eye Disease

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Uveitis; Scleritis
• Intervention / Treatment: Drug: tofacitinib

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in Saint Louis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tofacitinib Treatment; 11mg extended-release tofacitinib, once daily, oral	Drug: tofacitinib; tofacitinib extended release, 11mg, daily, oral; Other Names: TOFA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Failure (Composite Outcome)	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	180 days

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Lynn M Hassman, MD PhD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2019
• Primary Completion (Actual): December 1, 2019
• Study Completion (Anticipated): April 4, 2021

Study Registration Dates

• First Submitted: June 26, 2018
• First Submitted That Met QC Criteria: June 26, 2018
• First Posted (Actual): July 9, 2018

Study Record Updates

• Last Update Posted (Actual): February 1, 2021
• Last Update Submitted That Met QC Criteria: January 7, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Uveal Diseases; Scleral Diseases; Eye Diseases; Uveitis; Scleritis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: tofacitinib_eye_disease

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No