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E. Lucchini et al.
heterogeneous criteria for response were adopted across different studies (according to older or updated criteria); moreover, older studies included mostly chronic, pluri- refractory patients, while in the more recent studies patients with newly diagnosed/persistent ITP were also included. Finally, the ability to compare studies is often only partial because of different follow-up periods.
The data from placebo-controlled studies seem discour- aging, but some considerations should be made: in the experimental treatment and placebo arms, patients were allowed to continue corticosteroid therapy, which could have biased the results: in the placebo arms the ORR were 67% (39% CR)48 and 73% (46% CR).47 Probably a more meaningful observation is that the median time to relapse in patients who achieved an overall response was 36 weeks in the rituximab group and 7 weeks in the placebo group.48
The main criticism that only 20% to 30% of patients achieve long-term remission for more than 3-5 years deserves further consideration. The main “error” was probably the mistaken belief that rituximab could repre- sent the medical substitute of splenectomy: a single treat- ment administered once in a lifetime that could definitive- ly cure many or even most patients with ITP. In some groups of patients, it is worth considering that even a sus- tained response of 12-18 months can have a significant, positive effect on a patient’s quality of life: during this period of time, they do not have to take any ITP medica- tion and can avoid frequent hospital checks.
Furthermore, several clinical studies found that in young women a course of rituximab administered before the chronic phase (ITP duration <12 months) can lead to response rates and at least mid-term remission rates com- parable to those obtained with splenectomy. This finding suggests that at least in some selected patients the treat- ment outcome may be much better.
Retreatment with rituximab is effective in most cases, especially in patients who maintained the preceding remission for more than 12 months.
Biomarkers predictive of response, including the contro- versial role of anti-platelet antibody testing, are still lack- ing and further studies are needed for their establishment and subsequent application in clinical practice.
The efficacy and safety of combinations of treatment with rituximab and other agents, such as thromboietin- receptor agonists, immunosuppressive agents, agents tar- geting plasma cells or yet others, need to be better evalu- ated and proven in comparison studies with rituximab monotherapy.
As far as concerns different rituximab doses, compar- isons between the “standard dose” and “rheumatoid arthritis dose” did not reveal different results in terms of efficacy and toxicity. Low-dose rituximab could be equal- ly effective, although prospective studies comparing the standard dose and low doses are lacking.
Rituximab is a well-tolerated drug; serious side effects are extremely rare and life-threatening infectious compli- cations are usually only seen in patients with other con- comitant causes of immunodeficiency.
Conclusions
In conclusion, based on what has been published in the last 20 years, it is still difficult to give clear indications on when, to whom and how rituximab should be adminis- tered. In 2019, the choice of rituximab over other treat- ment options has to be weighed considering the individ- ual patient’s features and expectations, the disease’s char- acteristics, the availability of the drug and the single cen- ter’s experience.
The authors of this review think that rituximab still rep- resents a valuable therapeutic option for patients with ITP and, based on current knowledge, believe that it should be considered especially (although not exclusively) at an early stage of the disease, as second- or third-line therapy, in young patients (particularly young women) and in patients treated with curative purposes.
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