Health-Related Quality of Life in Patients with Primary Immune Thrombocytopenia (pITP): Investigating Differences Amongst Newly Diagnosed, Persistent and Chronic Pitp Patients
Authors: Efficace Fabio , Fazi Paola , Santoro Cristina , Gaidano Gianluca , Cottone Francesco , Borchiellini Alessandra , Carpenedo Monica , Simula Maria Pina , Di Giacomo Valeria , Pierri Ivana , Nobile Francesco , Rodeghiero Francesco , Scaramucci Laura , Rambaldi Alessandro , Cascavilla Nicola , Forghieri Fabio , Petrungaro Annamaria , Ditonno Paolo , La Nasa Giorgio , Cirrincione Sonia , Mandelli Franco , Mazzucconi Maria Gabriella 
Published: October 2019

Abstract
Introduction:
Very little is known about health-related quality of life (HRQOL) of patients diagnosed with primary Immune Thrombocytopenia (pITP). Also, the paucity of available data mainly stems from patients enrolled in randomized controlled trials thus limiting generalizability of findings to patients routinely seen in real world practice.
Aim:
The main objective of this study is to compare HRQOL of pITP patients with that of their peers from the general population and to investigate whether HRQOL differences exist among those classified as (Rodeghiero et al, Blood. 2009 Mar 12;113(11):2386-93): newly diagnosed, persistent and chronic pITP patients.
Methods:
Adult patients with pITP were consecutively enrolled, regardless of therapy, in 25 centers. All patients were invited by their treating physicians in the hospital. Consenting patients were requested to complete a battery of patient-reported outcome (PRO) questionnaires. The primary HRQOL outcome measure was the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). It consists of 36 items covering eight generic health status/QoL domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH).
To minimize possible bias in comparisons of pITP patients HRQOL outcomes to general population norms, a propensity score matching approach plus further regression adjustment was adopted to select the best possible case-control pairs. The group of potential controls was a representative sample of 1997 adults without the disease from a previous study which provided SF-36 population norms. Controls from these data were matched to pITP patients by an optimal nearest-neighbour matching algorithm based on age, sex, education, and geographic area. Multiple linear regression analyses were performed on the matched dataset to compute adjusted mean differences (α=0.05), using selected a priori key HRQOL confounders as covariates: age, sex, education, geographic area, and marital status. Effect sizes were computed and clinical significance of mean scores SF-36 differences was also estimated.
Results:
Out of 424 patients invited to participate, 420 returned the questionnaires (99% compliance). At study participation, mean age of patients was 54 years (range 18-89) with the majority being women (N=264, 64%). The mean platelet count at diagnosis was 27.6 x109/L and the mean platelet count at last medical visit, before the HRQOL assessment, was 119 x109/L. Two-hundred twenty patients (50%) had at least 1 comorbidity. At the time of HRQOL assessment there were 82%, 64% and 44% of patients receiving active treatments, respectively in the newly diagnosed, persistent and chronic pITP group. Splenectomy was performed in 8% and 22% of the persistent and chronic pITP patients, respectively. No statistically significant differences existed among the three disease groups with regard to age, gender and presence of comorbidity. When compared with their peers in the general population, worse statistically significant outcomes (P<0.05) were found for five out of the eight SF-36 scales. The largest clinically meaningful difference (Δ=16 points) was found for the RE scale. Comparison by disease group (each of which versus their respective peers in the general population), revealed greater HRQOL impairments in persistent pITP patients across all physical and mental health HRQOL domains. Differences between newly diagnosed and chronic pITP patients with their peers in the general populations were marginal. However, for persistent pITP patients medium to large impairments were found when compared with their peers in the following domains: PF (ES=0.87, P=0.001), RP (ES=0.93, P<0.001), and SF (ES=0.78, P=0.004), RE (ES=0.74, P=0.004), and MH (ES=0.55, P=0.026).
Conclusions:
Persistent pITP patients are those experiencing the most important limitations in both physical and mental HRQOL domains with respect to their peers from the general population. This information can help physicians to pay special attention to this patient group in their daily clinical practice.

Disclosures
Gaidano: Celgene: Research Funding; MorphoSys; Roche; Novartis; GlaxoSmithKline; Amgen; Janssen; Karyopharm: Honoraria, Other: Advisory boards. Rodeghiero:Celgene Corporation: Honoraria, Research Funding.