Physician decision making in selection of second‐line treatments in immune thrombocytopenia in children

Abstract

Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which presents with isolated thrombocytopenia and risk of hemorrhage. While most children with ITP promptly recover with or without drug therapy, ITP is persistent or chronic in others. When needed, how to select second-line therapies is not clear. ICON1, conducted within the Pediatric ITP Consortium of North America (ICON), is a prospective, observational, longitudinal cohort study of 120 children from 21 centers starting second-line treatments for ITP which examined treatment decisions. Treating physicians reported reasons for selecting therapies, ranking the top three. In a propensity weighted model, the most important factors were patient/parental preference (53%) and treatment-related factors: side effect profile (58%), long-term toxicity (54%), ease of administration (46%), possibility of remission (45%), and perceived efficacy (30%). Physician, health system, and clinical factors rarely influenced decision-making. Patient/parent preferences were selected as reasons more often in chronic ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003). Splenectomy and rituximab were chosen for the possibility of inducing long-term remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants, were chosen for ease of administration and expected adherence (P < .001). Physicians chose rituximab in patients with lower expected adherence (P = .017). Treatment choice showed some physician and treatment center bias. This study illustrates the complexity and many factors involved in decision-making in selecting second-line ITP treatments, given the absence of comparative trials. It highlights shared decision-making and the need for well-conducted, comparative effectiveness studies to allow for informed discussion between patients and clinicians.

Second‐line treatments in children with immune thrombocytopenia: Effect on platelet count and patient‐centered outcomes

“…Though splenectomy can offer a durable response rate of approximately 70%, the response cannot be predicted in a given patient, and there are associated risks . Providers enrolling in the ICON1 study reported that they chose splenectomy for its curative potential; however, very few were performed during the several years of this study . Splenectomy rates have been consistently declining over time with the increased use of pharmacologic therapies .…”

“…The mechanisms of action and the routes of administration are also considerations in the selection of these agents. Specific treatments are often selected by parent and/or patient preference which may be why patients showed an increase in HRQoL across treatments . If patients and families engage in the selection of their treatment, it will increase the likelihood that the therapy will match their lifestyles and goals, ultimately increasing HRQoL.…”

“…ICON1 is a longitudinal observational cohort of 120 children with ITP requiring second‐line treatments . Participants were enrolled at 21 centers in the United States and Canada between September 2013 and December 2015, following local institutional review board/research ethics board approval.…”

Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo‐controlled trials

“…Those who do not improve often cycle endlessly through the various treatment options. Despite the multiple agents available, there is an unmet medical need for patients with ITP …”

Association of a positive direct antiglobulin test with chronic immune thrombocytopenia and use of second line therapies in children: A multi‐institutional review

“…The results of DAT testing should become a part of discussions with families regarding the likelihood of their child's disease becoming chronic or needing second line agents; however, further study of DAT prognostic implications are needed. Management strategies for ITP vary greatly and are impacted by parent/patient preference, risk‐benefit assessment of individual therapies, physician preference and institutional standards of therapy . A positive DAT at baseline may be associated with development of chronic disease.…”