How Effective Are the Immunosuppressive Therapies Rituximab and Mycophenolate Mofetil in Immune Thrombocytopenia? Real World Evidence from the UK ITP Registry

Immune thrombocytopenia (ITP) is a rare condition characterised by thrombocytopenia and variable bleeding severity. After acute management with steroids and intravenous immunoglobulin (IVIG), next line therapies include medical treatments: immunosuppressive therapy such as rituximab,
mycophenolate mofetil (MMF), thrombopoietin receptor agonists
or surgical treatments. The choice of therapy depends on the time course of the disease, severity, patient choice and comorbidities. The evidence for comparative efficacy between different treatment modalities is lacking in the literature, in particular the immunosuppressive therapies MMF and rituximab.
The UK ITP registry is a national registry of primary ITP, capturing demographics, clinical features, treatments and comorbidities. As of July 2021, it has 4402 participants from 90 acute NHS Trusts across the UK. We analysed data from the UK adult ITP registry to assess responses to rituximab and MMF therapy. All patients entered into the registry from 1st January 2010 were included in this analysis. Internationally recognised definitions of response based on platelet count were used: partial response (PR) platelets >30 x109/L and double
baseline, complete response (CR) platelets >100 x109/L; No response – absence of CR and PR. In addition, we reviewed use of rescue therapy and use of additional therapies following treatment.

A total of 844 patients were included in the analysis, of these 486 had received rituximab and 358 had received MMF since 2010. The median follow up before treatment was 230.5 weeks for rituximab and 195 weeks for MMF. At the time of commencing rituximab (and within 4 weeks of starting), 26.1% patients were receiving prednisolone, 10% IVIG, 3% dexamethasone, 3.2% MMF, 2.95% romiplostim and 2.36% eltrombopag. At the time of commencing MMF (and within 4 weeks of starting), 39.2% patients were receiving prednisolone, 12.74 IVIG, 3.86% dexamethasone, 3.6 rituximab, 5.6% romiplostim and 3.86%
eltrombopag.

The total number of patients achieving platelet response at each time response are listed in
table 1. Of those receiving rituximab with baseline platelets <30 x109/L at starting therapy, 40% had at least PR by 4 weeks, 50% at 12 weeks and 30% at 12 months. For MMF, these percentages were 30%, 30% and 18% respectively, however, the numbers of patients in the MMF group were lower.
The median duration of response was 44 weeks for rituximab and 27 weeks for MMF. Where new therapies were required, the median number of weeks until therapy was switched was 18 weeks for rituximab and 15 weeks for MMF. 77% patients and 80.7% patients who received rituximab and MMF respectively changed treatment during their follow up. Overall 284 (58.4%) patients received rescue medication during follow up, of those that received MMF 234 (65.36%) received rescue medication. The main rescue therapies were prednisolone (589
episodes in rituximab group and 520 in MMF group) and IVIG (482 in rituximab group and 321 in MMF group).

In conclusion, this is one of the first studies, using real world data and long term follow up, to compare outcomes after immunosuppression. Both rituximab and MMF are often administered with additional therapies at the outset, predominantly steroids and IVIG, but also other therapies such as the thrombopoietin receptor agonists. The use of rescue therapies during follow up, suggesting treatment failure or a need to augment the response,
is common with most patients in both groups ultimately having treatment change during follow up. Extension of this study to include other therapies and identifying groups most likely to respond will support optimisation of treatment for patients with ITP.