Effect of Corticosteroid-Sparing Treatment with Mycophenolate Mofetil vs Methotrexate on Inflammation in Patients with Uveitis: A Randomized Clinical Trial

S. R. Rathinam, John A. Gonzales, Radhika Thundikandy, Anuradha Kanakath, S. Bala Murugan, R. Vedhanayaki, Lyndell L. Lim, Eric Suhler, Hassan A. Al-Dhibi, Thuy Doan, Jeremy D. Keenan, Maya M. Rao, Caleb D. Ebert, Hieu H. Nguyen, Eric Kim, Travis C. Porco, Nisha R. Acharya

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Importance: Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective. Objective: To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Design, Setting, and Participants: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018. Interventions: Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109). Main Outcomes and Measures: The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome. Results: Among 216 patients who were randomized (median age, 38 years; 135 (62.5%) women), 194 (89.8%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7%) patients in the methotrexate group vs 56 (57.1%) in the mycophenolate group (difference, 9.5% [95% CI, -5.3% to 21.8%]; odds ratio [OR], 1.50 [95% CI, 0.81 to 2.81]; P =.20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexate group vs 42 (55.3%) in the mycophenolate group (difference, 19.1% [95% CI, 3.6% to 30.6%]; OR, 2.35 [95% CI, 1.16 to 4.90]; P =.02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3%) in the methotrexate group vs 14 (63.6%) in the mycophenolate group (difference, -30.3% [95% CI, -51.6% to 1.1%]; OR, 0.29 [95% CI, 0.08 to 1.05]; P =.07; P for interaction =.004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexate group and 8 patients (7.4%) in the mycophenolate group. Conclusions and Relevance: Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis.

Original languageEnglish (US)
Pages (from-to)936-945
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume322
Issue number10
DOIs
StatePublished - Sep 10 2019

Fingerprint

Mycophenolic Acid
Uveitis
Methotrexate
Adrenal Cortex Hormones
Randomized Controlled Trials
Inflammation
Intermediate Uveitis
Panuveitis
Posterior Uveitis
Antimetabolites
Odds Ratio
Therapeutics
Immunomodulation
Saudi Arabia
Immunosuppressive Agents
Prednisone
Mexico
Treatment Failure
Pharmaceutical Preparations
Uncertainty

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of Corticosteroid-Sparing Treatment with Mycophenolate Mofetil vs Methotrexate on Inflammation in Patients with Uveitis : A Randomized Clinical Trial. / Rathinam, S. R.; Gonzales, John A.; Thundikandy, Radhika; Kanakath, Anuradha; Murugan, S. Bala; Vedhanayaki, R.; Lim, Lyndell L.; Suhler, Eric; Al-Dhibi, Hassan A.; Doan, Thuy; Keenan, Jeremy D.; Rao, Maya M.; Ebert, Caleb D.; Nguyen, Hieu H.; Kim, Eric; Porco, Travis C.; Acharya, Nisha R.

In: JAMA - Journal of the American Medical Association, Vol. 322, No. 10, 10.09.2019, p. 936-945.

Research output: Contribution to journalArticle

Rathinam, SR, Gonzales, JA, Thundikandy, R, Kanakath, A, Murugan, SB, Vedhanayaki, R, Lim, LL, Suhler, E, Al-Dhibi, HA, Doan, T, Keenan, JD, Rao, MM, Ebert, CD, Nguyen, HH, Kim, E, Porco, TC & Acharya, NR 2019, 'Effect of Corticosteroid-Sparing Treatment with Mycophenolate Mofetil vs Methotrexate on Inflammation in Patients with Uveitis: A Randomized Clinical Trial', JAMA - Journal of the American Medical Association, vol. 322, no. 10, pp. 936-945. https://doi.org/10.1001/jama.2019.12618
Rathinam, S. R. ; Gonzales, John A. ; Thundikandy, Radhika ; Kanakath, Anuradha ; Murugan, S. Bala ; Vedhanayaki, R. ; Lim, Lyndell L. ; Suhler, Eric ; Al-Dhibi, Hassan A. ; Doan, Thuy ; Keenan, Jeremy D. ; Rao, Maya M. ; Ebert, Caleb D. ; Nguyen, Hieu H. ; Kim, Eric ; Porco, Travis C. ; Acharya, Nisha R. / Effect of Corticosteroid-Sparing Treatment with Mycophenolate Mofetil vs Methotrexate on Inflammation in Patients with Uveitis : A Randomized Clinical Trial. In: JAMA - Journal of the American Medical Association. 2019 ; Vol. 322, No. 10. pp. 936-945.
@article{9ee702a6016043708661540a2ce3903c,
title = "Effect of Corticosteroid-Sparing Treatment with Mycophenolate Mofetil vs Methotrexate on Inflammation in Patients with Uveitis: A Randomized Clinical Trial",
abstract = "Importance: Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective. Objective: To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Design, Setting, and Participants: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018. Interventions: Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109). Main Outcomes and Measures: The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1{\%}, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome. Results: Among 216 patients who were randomized (median age, 38 years; 135 (62.5{\%}) women), 194 (89.8{\%}) completed follow-up through 6 months. Treatment success occurred in 64 (66.7{\%}) patients in the methotrexate group vs 56 (57.1{\%}) in the mycophenolate group (difference, 9.5{\%} [95{\%} CI, -5.3{\%} to 21.8{\%}]; odds ratio [OR], 1.50 [95{\%} CI, 0.81 to 2.81]; P =.20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4{\%}) in the methotrexate group vs 42 (55.3{\%}) in the mycophenolate group (difference, 19.1{\%} [95{\%} CI, 3.6{\%} to 30.6{\%}]; OR, 2.35 [95{\%} CI, 1.16 to 4.90]; P =.02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3{\%}) in the methotrexate group vs 14 (63.6{\%}) in the mycophenolate group (difference, -30.3{\%} [95{\%} CI, -51.6{\%} to 1.1{\%}]; OR, 0.29 [95{\%} CI, 0.08 to 1.05]; P =.07; P for interaction =.004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0{\%}) in the methotrexate group and 8 patients (7.4{\%}) in the mycophenolate group. Conclusions and Relevance: Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis.",
author = "Rathinam, {S. R.} and Gonzales, {John A.} and Radhika Thundikandy and Anuradha Kanakath and Murugan, {S. Bala} and R. Vedhanayaki and Lim, {Lyndell L.} and Eric Suhler and Al-Dhibi, {Hassan A.} and Thuy Doan and Keenan, {Jeremy D.} and Rao, {Maya M.} and Ebert, {Caleb D.} and Nguyen, {Hieu H.} and Eric Kim and Porco, {Travis C.} and Acharya, {Nisha R.}",
year = "2019",
month = "9",
day = "10",
doi = "10.1001/jama.2019.12618",
language = "English (US)",
volume = "322",
pages = "936--945",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "10",

}

TY - JOUR

T1 - Effect of Corticosteroid-Sparing Treatment with Mycophenolate Mofetil vs Methotrexate on Inflammation in Patients with Uveitis

T2 - A Randomized Clinical Trial

AU - Rathinam, S. R.

AU - Gonzales, John A.

AU - Thundikandy, Radhika

AU - Kanakath, Anuradha

AU - Murugan, S. Bala

AU - Vedhanayaki, R.

AU - Lim, Lyndell L.

AU - Suhler, Eric

AU - Al-Dhibi, Hassan A.

AU - Doan, Thuy

AU - Keenan, Jeremy D.

AU - Rao, Maya M.

AU - Ebert, Caleb D.

AU - Nguyen, Hieu H.

AU - Kim, Eric

AU - Porco, Travis C.

AU - Acharya, Nisha R.

PY - 2019/9/10

Y1 - 2019/9/10

N2 - Importance: Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective. Objective: To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Design, Setting, and Participants: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018. Interventions: Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109). Main Outcomes and Measures: The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome. Results: Among 216 patients who were randomized (median age, 38 years; 135 (62.5%) women), 194 (89.8%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7%) patients in the methotrexate group vs 56 (57.1%) in the mycophenolate group (difference, 9.5% [95% CI, -5.3% to 21.8%]; odds ratio [OR], 1.50 [95% CI, 0.81 to 2.81]; P =.20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexate group vs 42 (55.3%) in the mycophenolate group (difference, 19.1% [95% CI, 3.6% to 30.6%]; OR, 2.35 [95% CI, 1.16 to 4.90]; P =.02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3%) in the methotrexate group vs 14 (63.6%) in the mycophenolate group (difference, -30.3% [95% CI, -51.6% to 1.1%]; OR, 0.29 [95% CI, 0.08 to 1.05]; P =.07; P for interaction =.004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexate group and 8 patients (7.4%) in the mycophenolate group. Conclusions and Relevance: Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis.

AB - Importance: Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective. Objective: To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Design, Setting, and Participants: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018. Interventions: Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109). Main Outcomes and Measures: The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome. Results: Among 216 patients who were randomized (median age, 38 years; 135 (62.5%) women), 194 (89.8%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7%) patients in the methotrexate group vs 56 (57.1%) in the mycophenolate group (difference, 9.5% [95% CI, -5.3% to 21.8%]; odds ratio [OR], 1.50 [95% CI, 0.81 to 2.81]; P =.20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexate group vs 42 (55.3%) in the mycophenolate group (difference, 19.1% [95% CI, 3.6% to 30.6%]; OR, 2.35 [95% CI, 1.16 to 4.90]; P =.02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3%) in the methotrexate group vs 14 (63.6%) in the mycophenolate group (difference, -30.3% [95% CI, -51.6% to 1.1%]; OR, 0.29 [95% CI, 0.08 to 1.05]; P =.07; P for interaction =.004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexate group and 8 patients (7.4%) in the mycophenolate group. Conclusions and Relevance: Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis.

UR - http://www.scopus.com/inward/record.url?scp=85071985058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071985058&partnerID=8YFLogxK

U2 - 10.1001/jama.2019.12618

DO - 10.1001/jama.2019.12618

M3 - Article

C2 - 31503307

AN - SCOPUS:85071985058

VL - 322

SP - 936

EP - 945

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

IS - 10

ER -