Methotrexate and Mycophenolate Mofetil for UVEITIS

NCT01829295 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 11-082275U10EY021125
• Study Type: interventional
• Target: 216
• Locations: 5 countries
• Sites: 9

Brief Summary

In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial, the investigators propose to establish which immunosuppressive therapy, methotrexate or mycophenolate mofetil, is more effective as a first-line, corticosteroid-sparing agent for the treatment of non-infectious uveitis in a block-randomized, observer-masked, comparative effectiveness trial.

Conditions

Uveitis

Keywords

antimetabolite, noninfectious

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieving Treatment Success at 6 Months (Phase I, 0-6 Months)

  Controlled ocular inflammation (≤ 0.5+ anterior chamber cells, ≤ 0.5+ vitreous haze, no active retinal/choroidal lesions in both eyes) with 7.5 mg/day of oral prednisone and ≤ 2 drops/day of topical 1% prednisolone acetate.

  6 Months

Secondary Outcomes (2)

• Number of Participants Achieving Treatment Success at 12 Months on Same Medication (Phase I, 6-12 Months)

  12 Months

• Number of Participants Achieving Treatment Success After Switching to Other Medication (Phase II, 0-6 Months)

  6 Months

Study Arms (2)

Methotrexate

EXPERIMENTAL

oral methotrexate

Drug: Methotrexate; Drug: Prednisone

Mycophenolate Mofetil

EXPERIMENTAL

oral mycophenolate mofetil

Drug: Mycophenolate mofetil; Drug: Prednisone

Interventions

Mycophenolate mofetil DRUG

For the first two weeks, an introductory dose of 500 mg twice a day (BID) orally. After two weeks, the dose will be increased to 1.5 g BID.

Also known as: Cellcept

Mycophenolate Mofetil

Methotrexate DRUG

For the first two weeks, an introductory dose of 15 mg/week (7.5mg BID once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week)

Methotrexate

Prednisone DRUG

All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.

Methotrexate; Mycophenolate Mofetil

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All the following criteria must be met at enrollment:
• Historical non-infectious intermediate, anterior and intermediate, posterior or panuveitis in at least one eye
• Active inflammation within the last 180 days, defined by the presence of any of the following (in at least one eye) according to Standardization of Uveitis Nomenclature (SUN) criteria:
• ≥ 2+ anterior chamber cells
• ≥ 2+ vitreous haze
• active retinal or choroidal lesions
• Active inflammation at enrollment, defined by the presence of any of the following (in at least one eye) according to SUN criteria:
• ≥1+ anterior chamber cells and/or
• ≥1+ vitreous haze and/or
• active retinal/choroidal lesions
• At least one of the following criteria must be met before or at enrollment:
• Active inflammation after 4 weeks of high-dose (1mg/kg prednisone equivalent) corticosteroid treatment or 4 weeks following a regional corticosteroid injection
• Treatment with oral corticosteroids resulting in a reduction of inflammation, followed by an increase in inflammation (of at least 1 grade in anterior chamber cells or vitreous haze or a change of non-active to active lesions) when corticosteroid is tapered, in the 180 weeks prior to enrollment
• Active inflammation after long-acting corticosteroid injection 4 weeks to 180 days prior to enrollment
• Active inflammation after treatment with \>10mg/day oral prednisone for at least the past 90 days prior to enrollment

You may not qualify if:

• Any infectious cause of uveitis
• Prior immunosuppressive therapy other than corticosteroids in the past 12 months
• Prior intolerability or safety issues with methotrexate or mycophenolate mofetil
• Prior failure to control ocular or other inflammation using methotrexate or mycophenolate mofetil
• Prior biologic therapy at any time
• Media opacity (such as cataract and/or corneal scar) and/or extensive posterior synechiae such that examination of the posterior segment is not possible in both eyes
• Chronic hypotony (IOP \< 5 mm Hg for \> 3 months) in both eyes
• Periocular or intravitreal corticosteroid injection in the past 4 weeks
• Fluocinolone acetonide implant in either eye in \< 3 years
• Intraocular surgery in \< 30 days, or planning on getting surgery within the next 6 months
• Best spectacle-corrected visual acuity (BSCVA) of hand motions or worse in better eye
• \< 16 years of age at enrollment
• Planning to conceive during the study period, pregnant or breast-feeding (blood or urine pregnancy test for all females, excluding those who are post-menopausal is mandatory)\*
• Systemic autoimmune disease anticipated to dictate treatment course
• Abnormal Complete blood count (≤ 2,500 white blood cells and/or ≤ 75,000 platelets and/or ≤9 hemoglobin) within 4 weeks prior to enrollment\*

Sponsors & Collaborators

• University of California, San Francisco: lead
• Aravind Eye Hospitals, India: collaborator
• Oregon Health and Science University: collaborator
• Asociación para Evitar la Ceguera en México: collaborator
• Royal Victoria Eye and Ear Hospital: collaborator
• Northwestern University: collaborator
• National Eye Institute (NEI): collaborator
• King Khaled Eye Specialist Hospital: collaborator

Study Sites (9)

Francis I Proctor Foundation

San Francisco, California, 94143, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Oregon Health and Science University - Casey Eye Institute

Portland, Oregon, 97239, United States

Location

Royal Victorian Eye and Ear Hospital

Melbourne, Victoria, 3002, Australia

Location

Aravind Eye Hospital

Coimbatore, Tamil Nadu, India

Location

Aravind Eye Hospital

Madurai, Tamil Nadu, India

Location

Aravind Eye Hospital

Pondicherry, Tamil Nadu, India

Location

Asociacion Para Evita La Ceguera en Mexico

Mexico City, Mexico City, 04030, Mexico

Location

King Khaled Eye Specialist Hospital

Riyadh, Saudi Arabia

Location

Related Publications (27)

• Galor A, Jabs DA, Leder HA, Kedhar SR, Dunn JP, Peters GB 3rd, Thorne JE. Comparison of antimetabolite drugs as corticosteroid-sparing therapy for noninfectious ocular inflammation. Ophthalmology. 2008 Oct;115(10):1826-32. doi: 10.1016/j.ophtha.2008.04.026. Epub 2008 Jun 25.

  PMID: 18579209 BACKGROUND

• Siepmann K, Huber M, Stubiger N, Deuter C, Zierhut M. Mycophenolate mofetil is a highly effective and safe immunosuppressive agent for the treatment of uveitis : a retrospective analysis of 106 patients. Graefes Arch Clin Exp Ophthalmol. 2006 Jul;244(7):788-94. doi: 10.1007/s00417-005-0066-8. Epub 2005 Sep 15.

  PMID: 16163494 BACKGROUND

• Teoh SC, Hogan AC, Dick AD, Lee RW. Mycophenolate mofetil for the treatment of uveitis. Am J Ophthalmol. 2008 Nov;146(5):752-60, 760.e1-3. doi: 10.1016/j.ajo.2008.03.004. Epub 2008 May 2.

  PMID: 18455143 BACKGROUND

• Thorne JE, Jabs DA, Qazi FA, Nguyen QD, Kempen JH, Dunn JP. Mycophenolate mofetil therapy for inflammatory eye disease. Ophthalmology. 2005 Aug;112(8):1472-7. doi: 10.1016/j.ophtha.2005.02.020.

  PMID: 16061096 BACKGROUND

• Larkin G, Lightman S. Mycophenolate mofetil. A useful immunosuppressive in inflammatory eye disease. Ophthalmology. 1999 Feb;106(2):370-4. doi: 10.1016/S0161-6420(99)90078-7.

  PMID: 9951492 BACKGROUND

• Baltatzis S, Tufail F, Yu EN, Vredeveld CM, Foster CS. Mycophenolate mofetil as an immunomodulatory agent in the treatment of chronic ocular inflammatory disorders. Ophthalmology. 2003 May;110(5):1061-5. doi: 10.1016/S0161-6420(03)00092-7.

  PMID: 12750115 BACKGROUND

• Choudhary A, Harding SP, Bucknall RC, Pearce IA. Mycophenolate mofetil as an immunosuppressive agent in refractory inflammatory eye disease. J Ocul Pharmacol Ther. 2006 Jun;22(3):168-75. doi: 10.1089/jop.2006.22.168.

  PMID: 16808677 BACKGROUND

• Bom S, Zamiri P, Lightman S. Use of methotrexate in the management of sight-threatening uveitis. Ocul Immunol Inflamm. 2001 Mar;9(1):35-40. doi: 10.1076/ocii.9.1.35.3983.

  PMID: 11262666 BACKGROUND

• Dev S, McCallum RM, Jaffe GJ. Methotrexate treatment for sarcoid-associated panuveitis. Ophthalmology. 1999 Jan;106(1):111-8. doi: 10.1016/S0161-6420(99)90011-8.

  PMID: 9917790 BACKGROUND

• Foeldvari I, Wierk A. Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis. J Rheumatol. 2005 Feb;32(2):362-5.

  PMID: 15693100 BACKGROUND

• Gangaputra S, Newcomb CW, Liesegang TL, Kacmaz RO, Jabs DA, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT, Suhler EB, Thorne JE, Foster CS, Kempen JH; Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Methotrexate for ocular inflammatory diseases. Ophthalmology. 2009 Nov;116(11):2188-98.e1. doi: 10.1016/j.ophtha.2009.04.020. Epub 2009 Sep 12.

  PMID: 19748676 BACKGROUND

• Holz FG, Krastel H, Breitbart A, Schwarz-Eywill M, Pezzutto A, Volcker HE. Low-dose methotrexate treatment in noninfectious uveitis resistant to corticosteroids. Ger J Ophthalmol. 1992;1(3-4):142-4.

  PMID: 1483126 BACKGROUND

• Shah SS, Lowder CY, Schmitt MA, Wilke WS, Kosmorsky GS, Meisler DM. Low-dose methotrexate therapy for ocular inflammatory disease. Ophthalmology. 1992 Sep;99(9):1419-23. doi: 10.1016/s0161-6420(92)31790-7.

  PMID: 1407973 BACKGROUND

• Taylor SR, Habot-Wilner Z, Pacheco P, Lightman SL. Intraocular methotrexate in the treatment of uveitis and uveitic cystoid macular edema. Ophthalmology. 2009 Apr;116(4):797-801. doi: 10.1016/j.ophtha.2008.10.033.

  PMID: 19344827 BACKGROUND

• Daniel E, Thorne JE, Newcomb CW, Pujari SS, Kacmaz RO, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT, Suhler EB, Foster CS, Jabs DA, Kempen JH. Mycophenolate mofetil for ocular inflammation. Am J Ophthalmol. 2010 Mar;149(3):423-32.e1-2. doi: 10.1016/j.ajo.2009.09.026. Epub 2009 Dec 30.

  PMID: 20042178 BACKGROUND

• Sobrin L, Christen W, Foster CS. Mycophenolate mofetil after methotrexate failure or intolerance in the treatment of scleritis and uveitis. Ophthalmology. 2008 Aug;115(8):1416-21, 1421.e1. doi: 10.1016/j.ophtha.2007.12.011. Epub 2008 Jan 25.

  PMID: 18221998 BACKGROUND

• Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005 Sep;140(3):509-16. doi: 10.1016/j.ajo.2005.03.057.

  PMID: 16196117 BACKGROUND

• Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS, Nussenblatt RB, Stiehm ER, Tessler H, Van Gelder RN, Whitcup SM, Yocum D. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol. 2000 Oct;130(4):492-513. doi: 10.1016/s0002-9394(00)00659-0.

  PMID: 11024423 BACKGROUND

• Reddy AK, Miller DC, Sura AA, Rathinam SR, Gonzales JA, Thundikandy R, Kanakath A, Murugan B, Vedhanayaki R, Lim LL, Suhler EB, Doan T, Al-Dhibi HA, Goldstein DA, Arellanes-Garcia L, Acharya NR. Risk of failing both methotrexate and mycophenolate mofetil from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial. J Ophthalmic Inflamm Infect. 2023 Jun 9;13(1):29. doi: 10.1186/s12348-023-00350-5.

  PMID: 37294447 RESULT

• Chattopadhyay A, Rathinam SR, Gonzales JA, Kelly NK, Thundikandy R, Kanakath A, Murugan SB, Vedhanayaki R, Lim LL, Suhler EB, Al-Dhibi HA, Doan T, Ebert CD, Porco TC, Acharya NR; FAST Research Group. Association between Quality of Life and Visual Acuity in a Randomized Clinical Trial of Patients with Uveitis Taking Antimetabolites. Ocul Immunol Inflamm. 2024 Apr;32(3):301-309. doi: 10.1080/09273948.2023.2169714. Epub 2023 Feb 7.

  PMID: 36749914 RESULT

• Sura AA, Sun Y, Reddy AK, Rathinam SR, Gonzales JA, Thundikandy R, Vedhanayaki R, Kanakath A, Murugan B, Doan TA, Lim LL, Suhler EB, Al-Dhibi HA, Acharya NR; FAST Research Group. Reduced Dose Methotrexate and Mycophenolate Mofetil in Noninfectious Uveitis: A Sub-Analysis from the First-Line Antimetabolites as Steroid Sparing Therapy (FAST) Trial. Ocul Immunol Inflamm. 2024 Aug;32(6):955-960. doi: 10.1080/09273948.2023.2165949. Epub 2023 Jan 26.

  PMID: 36701644 RESULT

• Tsui E, Rathinam SR, Gonzales JA, Thundikandy R, Kanakath A, Balamurugan S, Vedhanayaki R, Lim LL, Suhler EB, Al-Dhibi HA, Doan T, Keenan J, Ebert CD, Kim E, Madow B, Porco TC, Acharya NR; FAST Research Group. Outcomes of Uveitic Macular Edema in the First-line Antimetabolites as Steroid-Sparing Treatment Uveitis Trial. Ophthalmology. 2022 Jun;129(6):661-667. doi: 10.1016/j.ophtha.2022.02.002. Epub 2022 Feb 8.

  PMID: 35143800 RESULT

• Kelly NK, Chattopadhyay A, Rathinam SR, Gonzales JA, Thundikandy R, Kanakath A, Murugan SB, Vedhanayaki R, Cugley D, Lim LL, Suhler EB, Al-Dhibi HA, Ebert CD, Berlinberg EJ, Porco TC, Acharya NR; FAST Research Group. Health- and Vision-Related Quality of Life in a Randomized Controlled Trial Comparing Methotrexate and Mycophenolate Mofetil for Uveitis. Ophthalmology. 2021 Sep;128(9):1337-1345. doi: 10.1016/j.ophtha.2021.02.024. Epub 2021 Mar 4.

  PMID: 33675850 RESULT

• Kong CL, Kelly NK, Sundararajan M, Rathinam SR, Gonzales JA, Thundikandy R, Vedhanayaki R, Kanakath A, Murugan B, Doan T, Goldstein D, Al-Dhibi HA, Acharya NR. Comparison of CD4 Counts with Mycophenolate Mofetil versus Methotrexate from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial. Ocul Immunol Inflamm. 2022 Jan 2;30(1):198-202. doi: 10.1080/09273948.2020.1774906. Epub 2020 Aug 11.

  PMID: 32779952 RESULT

• Rathinam SR, Gonzales JA, Thundikandy R, Kanakath A, Murugan SB, Vedhanayaki R, Lim LL, Suhler EB, Al-Dhibi HA, Doan T, Keenan JD, Rao MM, Ebert CD, Nguyen HH, Kim E, Porco TC, Acharya NR; FAST Research Group. Effect of Corticosteroid-Sparing Treatment With Mycophenolate Mofetil vs Methotrexate on Inflammation in Patients With Uveitis: A Randomized Clinical Trial. JAMA. 2019 Sep 10;322(10):936-945. doi: 10.1001/jama.2019.12618.

  PMID: 31503307 RESULT

• Bui AD, Kong CL, Kelly NK, Rathinam SR, Gonzales JA, Thundikandy R, Kanakath A, Murugan B, Vedhanayaki R, Lim LL, Suhler EB, Al-Dhibi HA, Doan T, Acharya NR; First-Line Antimetabolites as Steroid-Sparing Treatment Research Group. Time to Uveitis Control with Methotrexate and Mycophenolate Mofetil. Ophthalmology. 2022 Jun;129(6):721-723. doi: 10.1016/j.ophtha.2022.01.020. Epub 2022 Jan 25. No abstract available.

  PMID: 35085661 RESULT

• Sundararajan M, Rathinam SR, Thundikandy R, Kanakath A, Balamurugan S, Vedhanayaki R, Miller DC, Lim LL, Suhler EB, Al-Dhibi HA, Arellanes-Garcia L, Reddy AK, Feng S, Doan T, Porco TC, Shantha JG, Acharya NR, Gonzales JA. Association Between Baseline Macular Morphologic Features on Optical Coherence Tomography and Visual Outcomes in Patients with Vogt-Koyanagi-Harada Disease. Ocul Immunol Inflamm. 2025 Feb;33(2):263-270. doi: 10.1080/09273948.2024.2391420. Epub 2024 Aug 27.

  PMID: 39190826 DERIVED

MeSH Terms

Conditions

Uveitis

Interventions

Mycophenolic Acid; Methotrexate; Prednisone

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Nisha Acharya
• Organization: F.I. Proctor Foundation, UCSF

Nisha.Acharya@ucsf.edu

4154768131

Study Officials

• Nisha Acharya, MD, MS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2013
• First Posted: April 11, 2013
• Study Start: August 1, 2013
• Primary Completion: February 21, 2018
• Study Completion: August 9, 2018
• Last Updated: April 2, 2024
• Results First Posted: April 26, 2019

Record last verified: 2024-03

Locations

US (3); IN (3); AU (1); SA (1); ME (1)