Mycophenolate plus steroids: A new therapy for immune thrombocytopenia?

In patients newly diagnosed with immune thrombocytopenia (ITP), the first-line combination treatment of mycophenolate and corticosteroids was effective and well tolerated compared with corticosteroids alone, results of the UK-based Flight* trial showed.

“The standard-of-care (SoC) of corticosteroid alone has several downsides,” said study author Dr Charlotte Bradbury from the University of Bristol, Bristol, UK. “Not only do most patients have side effects from steroids, but there is also a heterogeneity of responses, with about 30 percent of patients not responding at all and the other patients most likely to relapse at some point in the future [with] only about 20 percent staying well in the long-term with this approach.”

Mycophenolate is frequently utilized in the UK as a second-line treatment for this condition. As such, the trial was conducted to assess if earlier initiation of mycophenolate could help prevent treatment failure, she said.

Participants in this multicentre, open-label trial were 120 patients aged >16 years (27.5 percent aged >70 years; mean age 54 years, 52.4 percent male) newly diagnosed with ITP (baseline platelet count <30 x10⁹/L; mean 7.2x10⁹/L). They were randomized 1:1 to receive SoC corticosteroid alone or in addition to mycophenolate. The mycophenolate dosing strategy was designed to be tapered and ceased 6 months following treatment initiation. The strategy for corticosteroid dosing followed international guidelines ie, dexamethasone pulses or prednisolone initial daily dose of 1 mg/kg then tapered. Patients were followed up for a mean 18 months.

Treatment failure, defined as a platelet count <30x10⁹/L and clinical need for second-line treatment (including relapsed and refractory ITP), was less common among patients who received corticosteroids plus mycophenolate compared with corticosteroids alone (22 percent vs 44 percent; adjusted hazard ratio [adjHR], 0.41, 95 percent confidence interval [CI], 0.21–0.80; p=0.0064). [ASH 2020, abstract LBA-2]

The results were consistent after excluding patients with secondary ITP from the analysis (adjHR, 0.37, 95 percent CI, 0.19–0.71; p=0.0029).

Bleeding events occurred at a similar rate between mycophenolate and corticosteroid-only recipients (22.0 percent vs 24.6 percent; p=0.83), as did gastrointestinal side effects (33.9 percent vs 24.6 percent; p=0.32) and hospital admission (11 vs 9 patients; p=0.63).

Fourteen patients in each group experienced infection and four patients in the corticosteroid-only group experienced neutropenia. Weight gain occurred in 28.8 and 34.4 percent of patients in the mycophenolate and corticosteroid-only groups, respectively, mood change or psychiatric disorders in 30.5 and 34.4 percent, respectively, and sleeping difficulties in 35.6 and 27.9 percent, respectively.

The side effects were predominantly related to corticosteroids, noted Bradbury. “It didn’t seem like mycophenolate was adding much in the way of side effects.”

Three patients in the mycophenolate and one in the corticosteroid-only group received blood transfusions, and two mycophenolate recipients received platelet transfusions. Five and six patients, respectively, received tranexamic acid, and eight and ten, respectively, received intravenous immunoglobulin.

A new treatment measure?

“[This, the first randomized trial assessing mycophenolate treatment in ITP showed that] mycophenolate may be considered an effective, well-tolerated first-line treatment option, alongside a short course of steroids, for some patients with ITP, approximately halving the risk of refractory or relapsed ITP,” said Bradbury and co-authors.

However, certain quality of life (QoL) outcomes, such as physical role or function and fatigue, were worse in the mycophenolate than the corticosteroid-only group. “This is an important reminder that disease response and patient experience may not correlate and emphasizes the importance of including patient-reported outcomes within trials,” they added.

Nonetheless, Bradbury stopped short of recommending the mycophenolate-corticosteroid combo as a first-line SoC, and not just because of the QoL outcomes. “[O]ver half of the patients treated with corticosteroids alone remained in first remission at follow-up, so potentially had they received mycophenolate, over half may have been overtreated.”

“The key would be to try and better stratify patients at diagnosis and try and target mycophenolate for those who would be expected to do poorly on corticosteroids alone,” she concluded.