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The addition of mycophenolate mofetil (MMF) to a glucocorticoid as a first-line treatment for immune thrombocytopenia (ITP) resulted in greater responses and a reduced risk of relapse or refractory disease, according to the results of a randomized controlled trial.

Patients treated with the MMF/glucocorticoid combination had half the number of treatment failures compared with patients who received glucocorticoids only (22% vs 44%, respectively; HR 0.41, 95% CI 0.21-0.80), reported Charlotte A. Bradbury, MD, PhD, of Bristol Hematology and Oncology Centre in England, and colleagues.

In addition, as shown in the team's study in the , patients treated with the combination achieved a greater response, with 91.5% having platelet counts over 100 × 10⁹/L compared with 63.9% of patients in the glucocorticoid-only group.

Physical function and fatigue, however, were worse for patients in the MMF group, the researchers reported.

In an , Paula H.B. Bolton-Maggs, DM, of the University of Manchester in England, and James N. George, MD, of the University of Oklahoma Health Sciences Center in Oklahoma City, said the quality-of-life findings should serve as "an important reminder that immune thrombocytopenia is not just about the platelet count and that randomized trials can produce unexpected findings that warrant further research."

James Bussel, MD, of Weill Cornell Medicine in New York City, who was not involved in the study, said he found MMF's impact on physical function and fatigue "a bit of a surprise."

"You would have thought the quality-of-life aspect would have been improved, theoretically, because people were doing better," he told 番茄社区.

The findings are nevertheless important, Bussel said, "and, hopefully, will lead to more studies to help determine what is the best thing to do upfront, especially if it reduces the amount of steroids, because that is the number one thing that patients object to."

Bradbury and colleagues noted that "the quality-of-life differences do not seem to be explained by specific side effects of mycophenolate mofetil, such as infection or diarrhea. Possible reasons include the length of treatment with mycophenolate mofetil, with a potential psychological effect related to treatment duration."

The group explained that the recommended first-line treatment for ITP has long been high-dose glucocorticoids, but there are serious drawbacks, including varying responses, high relapse rates, and side effects that can result in treatment disruption or discontinuation. MMF has been widely used in the U.K. as a second-line treatment for ITP, showing some efficacy in refractory disease.

For their study, Bradbury's team randomized 120 patients with ITP in a 1:1 fashion to receive MMF with a glucocorticoid or a glucocorticoid alone. The mean age of participants was 54 (range 17-87), 54% were male, and the mean pretreatment platelet count at baseline was 7 × 10⁹/L. The majority of patients in each group received prednisolone as the first-line glucocorticoid, while the remaining patients received dexamethasone.

MMF treatment began with a dose of 500 mg twice daily for 2 weeks, followed by 750 mg twice daily if the patient had no side effects. Four weeks after initiation of treatment, the dose was increased to 1 g twice daily if the patient had no side effects. After 6 months, the dose for all patients who had a complete response to MMF was reduced by 250 mg each month, while continuing with the lowest dose that achieved a hematologically safe platelet count.

The primary outcome was treatment failure (platelet count of less than 30 × 10⁹/L and initiation of a second-line treatment), while secondary outcomes included response rates, side effects, occurrence of bleeding, patient-reported quality-of-life measures, and serious adverse events.

Of the 40 treatment failures reported in the study, 13 were in the MMF group and 27 were in the glucocorticoid-only group. A sensitivity analysis controlling for age, sex, obesity, and type of ITP (i.e., primary or secondary) resulted in an adjusted HR of 0.40 (95% CI 0.20-0.78).

Other secondary outcomes were as follows, the investigators reported:

• 93.2% of MMF patients had platelet counts over 30 × 10⁹/L, compared with 75.4% in the glucocorticoid-only group

• 6.8% of patients in the MMF group had ITP that was refractory to treatment, compared with 24.6% of patients in the glucocorticoid-only group

• There were no differences between the groups in the occurrence of bleeding, rescue treatments, or side effects

Over 12 months of follow-up, patients in the MMF group reported worse fatigue and had lower scores regarding physical function.

A study limitation, the researchers said, was the open-label design.

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