Combined treatment with mycophenolate improves response in Graves' orbitopathy
In patients with Graves’ orbitopathy, adding the immunosuppressant drug mycophenolate to glucocorticoid therapy appeared to improve treatment response compared with methylprednisolone alone, according to results of a randomized clinical trial.
“The 2016 European Thyroid Association guidelines recommend intravenous methylprednisolone pulse therapy as first-line treatment for active and severe Graves’ orbitopathy,” George J. Kahaly, MD, PhD, of Johannes Gutenberg University Medical Center, Mainz, Germany, and colleagues wrote. “However, some patients do not respond or relapse after completion of steroid treatment. There is therefore a need to identify new therapeutic strategies, including combination therapies.”
Kahaly and colleagues performed an observer-masked, block-randomized, center-stratified trial of 164 patients with moderate to severe Graves’ orbitopathy at two centers in Germany and two in Italy. Patients were randomly assigned to a course of methylprednisolone (500 mg per week for 6 weeks followed by 250 mg per week for another 6 weeks) alone (n = 81) or with 360 mg of oral mycophenolate twice daily for 24 weeks (n = 83). The main outcomes were rate of response at 12 weeks and rate of relapse at 24 and 36 weeks. The researchers evaluated response at weeks 24 and 36 in post-hoc analyses.
At 12 weeks, 36 of 73 (49%) patients in the monotherapy group showed a response to treatment, compared with 48 of 76 (63%) in the combination therapy group, Kahaly and colleagues reported (OR = 1.76; 95% CI, 0.92-3.39). At 24 weeks, more than half of the monotherapy group responded to treatment (53%; n = 38 of 72 remaining patients), along with nearly three-quarters of the combination therapy group (71%; n = 53 of 75 remaining patients).
However, four patients in the monotherapy group (11%) and four in the combination therapy group (8%) relapsed at 24 weeks (OR = 0. 71; 95% CI, 0.17-3.03). Further, another three patients in the monotherapy group (8%) and two in the combination group (4%) relapsed at week 36 (OR = 0.65; 95% CI, 0.12-3.44).
More than 40% of patients assigned to monotherapy (n = 31 of 68 remaining patients; 46%) and more than half in the combination group (n = 49 of 73 remaining patients; 67%) demonstrated a sustained response at week 36 (OR = 2.44; 95% CI, 1.23-4.82).
The researchers reported 24 serious adverse events in 23 different patients. Of these, 11 occurred among 10 patients assigned to combination therapy and 13 events among 13 patients assigned to monotherapy. Twenty percent of patients in the monotherapy group experienced mild to moderate adverse events, compared with 25% in the combination therapy group.
“The addition of a moderate daily oral dose of mycophenolate to an established moderate dose of intravenous methylprednisolone did not significantly affect the rate of response at 12 weeks or rate of relapse at 24 and 36 weeks,” the researchers wrote. “However, this add-on mycophenolate did lead to significant improvements in patients’ quality of life and, in our post-hoc analysis, ophthalmic symptoms and signs.” – by Andy Polhamus
Disclosures: Kahaly reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.