Two uveitis treatment options yield similar success

Approximately two-thirds of adults with uveitis achieved inflammation control after 6 months on either methotrexate or mycophenolate alongside a reduction in corticosteroid use in an international, multicenter, open-label, randomized trial.

“The findings of this trial have implications for clinical practice because they provide scientific justification that mycophenolate mofetil is not more effective than methotrexate as a corticosteroid-sparing immunosuppressive therapy for uveitis,” wrote S.R. Rathinam, MD, PhD, of Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, India, and colleagues.

Although corticosteroid therapy is the first-line treatment for uveitis, adverse effects limit long-term use. Mycophenolate mofetil and methotrexate are options for corticosteroid-sparing immunosuppressive therapy for uveitis, but their effectiveness has not been compared until the current study, they said.

In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) trial published Sept. 10 in JAMA, the researchers randomized 216 adults with uveitis (a total of 407 eyes with uveitis) to 25 mg of weekly oral methotrexate or 1.5 g of twice-daily oral mycophenolate mofetil at nine referral eye care centers in India, the United States, Australia, Saudi Arabia, and Mexico; the investigators were masked to the treatment assignment.

Patients with treatment success continued taking their randomized medication for another 6 months. If treatment failed, patients switched to the other antimetabolite with another 6-month follow-up. Overall, 84%-93% in each group had bilateral uveitis. Forty-six patients (21%) had intermediate uveitis only or anterior uveitis and intermediate uveitis, and 170 patients (79%) had posterior uveitis or panuveitis. The median age of the patients was 36 years in the methotrexate group and 41 years in the mycophenolate group; other demographic characteristics were similar between the groups.

 

Overall, 64 patients given methotrexate (67%) and 56 of those given mycophenolate (57%) achieved treatment success at 6 months. Treatment success included inflammation control defined as “less than or equal to 0.5+ anterior chamber cells by Standardization of Uveitis Nomenclature criteria, less than or equal to 0.5+ vitreous haze clinical grading using the National Eye Institute scale, and no active retinal or choroidal lesions,” as well as needing no more than 7.5 mg of prednisone daily and two drops or less of prednisolone acetate 1% per day, and reporting no intolerability or safety concerns requiring study discontinuation.

Adverse events were similar between the groups. The most common nonserious adverse events were fatigue and headaches, and the most common nonserious laboratory adverse event was elevated liver enzymes. Fourteen serious adverse events occurred during the study period; three in the methotrexate group and two in the mycophenolate group were deemed drug related and all were elevated liver function tests.

The study findings had several limitations, including lack of masking of the patients to the medication and an inability to compare between types of uveitis, the researchers noted. Avenues for further research include whether one of the drugs is more effective based on the uveitis subtype, they added.

The study was supported in part by the National Eye Institute and study drugs were provided by the University of California San Francisco Pharmacy. Dr. Rathinam disclosed grants from Aravind Eye Hospital, and several coauthors disclosed relationships with AbbVie, Allergan, Novartis, Novotech, and Bayer.

SOURCE: Rathinam SR et al. JAMA. 2019;322(10):936-45. doi: 10.1001/jama.2019.12618.

Approximately two-thirds of adults with uveitis achieved inflammation control after 6 months on either methotrexate or mycophenolate alongside a reduction in corticosteroid use in an international, multicenter, open-label, randomized trial.

“The findings of this trial have implications for clinical practice because they provide scientific justification that mycophenolate mofetil is not more effective than methotrexate as a corticosteroid-sparing immunosuppressive therapy for uveitis,” wrote S.R. Rathinam, MD, PhD, of Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, India, and colleagues.

Although corticosteroid therapy is the first-line treatment for uveitis, adverse effects limit long-term use. Mycophenolate mofetil and methotrexate are options for corticosteroid-sparing immunosuppressive therapy for uveitis, but their effectiveness has not been compared until the current study, they said.

In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) trial published Sept. 10 in JAMA, the researchers randomized 216 adults with uveitis (a total of 407 eyes with uveitis) to 25 mg of weekly oral methotrexate or 1.5 g of twice-daily oral mycophenolate mofetil at nine referral eye care centers in India, the United States, Australia, Saudi Arabia, and Mexico; the investigators were masked to the treatment assignment.

Patients with treatment success continued taking their randomized medication for another 6 months. If treatment failed, patients switched to the other antimetabolite with another 6-month follow-up. Overall, 84%-93% in each group had bilateral uveitis. Forty-six patients (21%) had intermediate uveitis only or anterior uveitis and intermediate uveitis, and 170 patients (79%) had posterior uveitis or panuveitis. The median age of the patients was 36 years in the methotrexate group and 41 years in the mycophenolate group; other demographic characteristics were similar between the groups.

 

Overall, 64 patients given methotrexate (67%) and 56 of those given mycophenolate (57%) achieved treatment success at 6 months. Treatment success included inflammation control defined as “less than or equal to 0.5+ anterior chamber cells by Standardization of Uveitis Nomenclature criteria, less than or equal to 0.5+ vitreous haze clinical grading using the National Eye Institute scale, and no active retinal or choroidal lesions,” as well as needing no more than 7.5 mg of prednisone daily and two drops or less of prednisolone acetate 1% per day, and reporting no intolerability or safety concerns requiring study discontinuation.

Adverse events were similar between the groups. The most common nonserious adverse events were fatigue and headaches, and the most common nonserious laboratory adverse event was elevated liver enzymes. Fourteen serious adverse events occurred during the study period; three in the methotrexate group and two in the mycophenolate group were deemed drug related and all were elevated liver function tests.

The study findings had several limitations, including lack of masking of the patients to the medication and an inability to compare between types of uveitis, the researchers noted. Avenues for further research include whether one of the drugs is more effective based on the uveitis subtype, they added.

The study was supported in part by the National Eye Institute and study drugs were provided by the University of California San Francisco Pharmacy. Dr. Rathinam disclosed grants from Aravind Eye Hospital, and several coauthors disclosed relationships with AbbVie, Allergan, Novartis, Novotech, and Bayer.

SOURCE: Rathinam SR et al. JAMA. 2019;322(10):936-45. doi: 10.1001/jama.2019.12618.

Approximately two-thirds of adults with uveitis achieved inflammation control after 6 months on either methotrexate or mycophenolate alongside a reduction in corticosteroid use in an international, multicenter, open-label, randomized trial.

“The findings of this trial have implications for clinical practice because they provide scientific justification that mycophenolate mofetil is not more effective than methotrexate as a corticosteroid-sparing immunosuppressive therapy for uveitis,” wrote S.R. Rathinam, MD, PhD, of Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, India, and colleagues.

Although corticosteroid therapy is the first-line treatment for uveitis, adverse effects limit long-term use. Mycophenolate mofetil and methotrexate are options for corticosteroid-sparing immunosuppressive therapy for uveitis, but their effectiveness has not been compared until the current study, they said.

In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) trial published Sept. 10 in JAMA, the researchers randomized 216 adults with uveitis (a total of 407 eyes with uveitis) to 25 mg of weekly oral methotrexate or 1.5 g of twice-daily oral mycophenolate mofetil at nine referral eye care centers in India, the United States, Australia, Saudi Arabia, and Mexico; the investigators were masked to the treatment assignment.

Patients with treatment success continued taking their randomized medication for another 6 months. If treatment failed, patients switched to the other antimetabolite with another 6-month follow-up. Overall, 84%-93% in each group had bilateral uveitis. Forty-six patients (21%) had intermediate uveitis only or anterior uveitis and intermediate uveitis, and 170 patients (79%) had posterior uveitis or panuveitis. The median age of the patients was 36 years in the methotrexate group and 41 years in the mycophenolate group; other demographic characteristics were similar between the groups.

 

Overall, 64 patients given methotrexate (67%) and 56 of those given mycophenolate (57%) achieved treatment success at 6 months. Treatment success included inflammation control defined as “less than or equal to 0.5+ anterior chamber cells by Standardization of Uveitis Nomenclature criteria, less than or equal to 0.5+ vitreous haze clinical grading using the National Eye Institute scale, and no active retinal or choroidal lesions,” as well as needing no more than 7.5 mg of prednisone daily and two drops or less of prednisolone acetate 1% per day, and reporting no intolerability or safety concerns requiring study discontinuation.

Adverse events were similar between the groups. The most common nonserious adverse events were fatigue and headaches, and the most common nonserious laboratory adverse event was elevated liver enzymes. Fourteen serious adverse events occurred during the study period; three in the methotrexate group and two in the mycophenolate group were deemed drug related and all were elevated liver function tests.

The study findings had several limitations, including lack of masking of the patients to the medication and an inability to compare between types of uveitis, the researchers noted. Avenues for further research include whether one of the drugs is more effective based on the uveitis subtype, they added.

The study was supported in part by the National Eye Institute and study drugs were provided by the University of California San Francisco Pharmacy. Dr. Rathinam disclosed grants from Aravind Eye Hospital, and several coauthors disclosed relationships with AbbVie, Allergan, Novartis, Novotech, and Bayer.

SOURCE: Rathinam SR et al. JAMA. 2019;322(10):936-45. doi: 10.1001/jama.2019.12618.