Clinical Epidemiology and First-Line Treatment in Immune Thrombocytopenia Adults. Results of the Carmen Prospective Cohort

Background: The clinical epidemiology of immune thrombocytopenia (ITP) is not well known. Some issues (bleeding events at diagnosis, association to other autoimmune diseases, rate of infection prior to ITP onset) are not well described in adults. Little is known as regards first-line treatment choice in the real-life practice.

Aim: The aims of this study were to assess i) the clinical epidemiology of incident ITP adults; ii) the use of first-line treatments in this population; and iii) the factors associated with the initial use of intravenous (IV) corticosteroids (CS) and of intravenous immunoglobulin (IVIg) in a real-life setting. This study was carried out on behalf of the French national center for autoimmune cytopenia and the French national center for rare diseases in immunohematology.

Methods: Study population was the patients included between June 2013 and December 2014 in the CARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) multicenter registry. This multicenter registry is carried out on behalf of the French national center for autoimmune cytopenia and the French national center for rare diseases in immunohematology. The originalities of this registry are: the prospective follow-up of newly diagnosed ITPs, aimed at completeness of recording in the French Midi-Pyrénées region, South of France (3 million inhabitants), and the detailed recording of ITP treatment exposures. All the physicians in charge of ITP patients in the region, belonging to the netwotk of the regional center for autoimmune cytopenia, prospectively follow every patient newly diagnosed for ITP during routine visit or hospital stay. ITP is defined in accordance with French guidelines: platelet count <150 x 10⁹/L and exclusion of other causes of thrombocytopenia. In this study, we assessed the clinical epidemiology at ITP onset, as well as ITP treatment use during the week following the diagnosis. Logistic regression models were performed to assess the factors associated with the use of IV CS and of IVIg. The following covariates were included: age, gender, Charlson's comorbidity score, secondary vs. primary ITP, bleeding score and platelet count.

Results: Out of 121 newly diagnosed ITP, 113 patients were followed in the region and gave informed consent. Median age was 65 years (range: 18-95). Half of the patients were female, 24 (21.3%) had a secondary ITP, 57 (50.4%) had a Charlson's score ≥1, median platelet count was 17 x10⁹/L (range: 1-126); 57 (50.9%) had bleeding symptoms, including 2 severe gastro-intestinal tract and 1 intracranial bleeding. Median Khellaf's bleeding score was 5 (range: 0-35). Twenty-five (21.4%) patients had another autoimmune disease (mostly: Hashimoto's thyroiditis, n=6, Sjögren syndrome, n=5, Evans syndrome, n=3) and 23 (20.3%) experienced an infection within the six weeks before ITP onset (including 8 influenza-like and 3 gastro-enteritis like syndromes, the others being various bacterial infections). Sixty-eight (60.2%) patients were treated during the week following the diagnosis. Among them, 66 (98.5%) received CS (median dose: 0.99 mg/kg/d), including 21 (31.3%) IV CS, 29 (43.3%) IVIg, 8 (11,9%) platelet transfusion, 2 romiplostim and 1 rituximab. The factors associated with the use of IV CS were secondary ITP (OR: 5.91; 95% CI: [1.78-19.71]) and Khellaf's bleeding score >8 (OR: 4.09; 95% CI [0.96-17.35]). Those associated with the use of IVIg were Khellaf's bleeding score >8 (OR: 7.30; 95% CI [1.36-32.27]) and platelet count <10 x 10⁹/L (OR: 3.95; 95% CI [1.77-13.29]).

Conclusions: This prospective cohort of newly diagnosed ITP adults confirms that severe bleeding is rare at ITP onset. Associated autoimmune diseases and recent infections are frequent. IVIg and IV CS were frequently used, particularly in case of severe bleeding.