Individuals with moderate to severe Graves’ orbitopathy may have an improved response to therapy at 24 and 36 weeks when treated with both methylprednisolone and mycophenolate compared with those treated with methylprednisolone alone, according to a study published in Lancet Diabetes & Endocrinology.
Researchers recruited a total of 154 individuals from a 4 centers (2 in Germany and 2 in Italy) and conducted an observer-masked, multicenter, block-randomized, center-stratified trial to compare the safety and efficacy of adding mycophenolate to the standard treatment of intravenous methylprednisolone in the treatment of moderate to severe Graves’ orbitopathy.
Individuals were randomly assigned 1:1 to 2 treatment groups: one group (n=75) received methylprednisolone alone (500 mg once per week for 6 weeks followed by 250 mg per week for 6 weeks), and the other (n=79) received methylprednisolone with mycophenolate (one 360 mg tablet twice per day for 24 weeks). The purpose of the study was to examine the response rate at week 12 of therapy and the relapse rates at 24 and 36 weeks, with a post-hoc response to therapy examined at week 24.
At week 12, individuals in the methylprednisolone plus mycophenolate and the methylprednisolone alone groups had response rates of 48/76 (63%) and 36/73 (49%), respectively (OR 1.76; 95% CI, 0.92-3.39, P =.089). Post hoc analysis at week 24 was 53/75 (71%) and 38/72 (53%), respectively (OR 2.16; 95% CI, 1.09-4.25, P =.026), and at week 36 was 49/73 (67%) and 31/68 (46%), respectively (OR 2.44, 1.23-4.28, P =.011).
Overall, ophthalmic improvements were seen in both treatment groups at weeks 12, 24, and 36, with a higher number of individuals in the methylprednisolone plus mycophenolate group experiencing improvements. Statistically significant improvements were noted only at weeks 24 and 36 in the post hoc analysis for those in the methylprednisolone plus mycophenolate group. In total, 90/147 (61%) individuals experienced a response to monotherapy or combination therapy when assessed at week 36.
Relapse rates for methylprednisolone alone and methylprednisolone plus mycophenolate at week 24 were found to be 4/38 (11%) and 4/53 (8%), respectively (OR 0.71; 95% CI 0.17-3.03, P =.72); and in 3 (8%) and 2 (4%) more patients, respectively, at week 36 (OR 0.65; 95% CI 0.12-3.44, P =.61). Quality of life scores improved significantly in both treatment groups.
Researchers concluded that while there were no statistically significant differences between treatment groups noted at week 12 of therapy or in the relapse rates at 24 and 36 weeks, the post hoc analysis at weeks 24 and 36 revealed a statistically significant improvement in ophthalmic signs and symptoms in the combined therapy group. Relapse rate and safety profile were similar for both treatment groups. Therefore, clinicians may consider the use of the combined therapy of methylprednisolone plus mycophenolate as an effective treatment option in individuals with active moderate to severe Graves’ orbitopathy and no contraindications for mycophenolate sodium.
Disclosure: This study was funded by Novartis.
Kahaly GJ, Riedl M, König J, et al; European Group on Graves’ Orbitopathy (EUGOGO). Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves’ orbitopathy (MINGO): a randomised, observer-masked, multicentre trial [published online January 30, 2018]. Lancet Diabetes Endocrinol. doi: 10.1016/S2213-8587(18)30020-2