ALBERT

Description: Background: In preclinical studies, eltrombopag has been associated to an increased incidence of cataract in mice and rats. No increased risk has been observed in randomized controlled trials in immune thrombocytopenia (ITP) patients. During the eltrombopag extension study EXTEND, 28/302 patients developed or worsened cataract, i.e. 9.3% of the patients over a median duration of exposure of 2.4 years. Of note, 79% of these 28 patients had at least another risk factor of cataract. Real-life studies assessing the risk of cataract in ITP adult patients exposed to eltrombopag are lacking. Aim: To assess the risk of cataract with eltrombopag in a nationwide cohort of primary ITP adults. Methods: The population was the cohort of all incident primary ITP adult patients (≥18 years) in France from June 2010 (date of eltrombopag marketing in France) to June 2017. This cohort was identified within the national health insurance database using a validated algorithm combining drug exposures and international classification of diseases, version 10 (ICD-10) diagnosis codes (FAITH cohort; NCT03429660). A nested case-control study was conducted within the cohort. Cases were patients who had a surgery for cataract after ITP onset, identified using appropriate codes. Up to five controls for each case were matched on age and sex. Index date was the date of cataract surgery for cases, and the date of cataract surgery of the corresponding case for controls. Two analyses were conducted: one considering the exposure to eltrombopag as ever vs. never exposed; another considering the cumulative exposure to eltrombopag, categorized by never exposed, a 1-365 Defined Daily Dose (DDD) exposure, and a ≥365 DDD exposure. Covariables were the presence of diabetes mellitus, cumulative exposure to corticosteroids considered in prednisone equivalence dosage (by quartiles), and the presence of ophthalmological risk factors of cataract (including previous ophthalmological surgery, glaucoma and other anterior chamber risk factors). Conditional logistic regression models were used to compute adjusted odds ratios (aOR) and their 95% confidence intervals (CI). Results: The cohort included 8,502 incident primary ITP adults. During the follow-up (31,590 patient-years in total; mean follow-up: 44.4 months), 1,097 patients were exposed to eltrombopag, including 310 with a cumulative exposure ≥365 DDDs. Overall, 573 patients had a surgery of cataract; incidence: 1.90/100 person-years (95% CI: 1.75-2.06). Fifty-seven cases occurred in patients ever exposed to eltrombopag; incidence: 1.50/100 person-years (95%CI: 1.15-1.94) in this subgroup. The nested case-control study included the 573 cases and 2699 controls. Median age was 75 years and 50% were women; the median duration of disease was 24.8 months in cases and 24.2 months in controls; 57 (9.9%) cases and 314 (11.6%) controls were exposed to eltrombopag before the index date; 14 (2.4%) and 68 (2.5%) patients had cumulative exposure to eltrombopag ≥365 DDDs, respectively. Cases were more frequently exposed to corticosteroids (83.4% vs. 75.7%), with a higher cumulative exposure to corticosteroids (median: 2800 vs. 2188 mg prednisone equivalent). Diabetes mellitus was present in 25.7% of cases vs. 25.1% of controls while ophthalmological risk factors were present in 5.4% and 2.8%, respectively. In the ever/never exposed analysis, the aOR for eltrombopag was 0.79 (95% CI: 0.58-1.07). In the cumulative exposure analysis, the aOR was 0.76 (95% CI: 0.54-1.08) in the 1-365 DDD group as compared with the never exposed group, and 0.88 (95% CI: 0.49-1.59) in the ≥365 DDD group as compared with the never exposed group. Conclusions: This nationwide pharmacoepidemiological study did not identify an increased risk of cataract in primary ITP adult patients exposed to eltrombopag. Disclosures Moulis: Novartis pharma: Research Funding, Speakers Bureau; Amgen pharma: Research Funding, Speakers Bureau; CSL Behring: Research Funding.

Description: Background: No study has specifically assessed the risk factors of infection in immune thrombocytopenia (ITP) patients in the era of rituximab therapy. Similarly, the protective effect of pneumococcal and influenza vaccines is unknown in real-life settings. Aim: The objective of this study was to assess the risk factors of serious infection (SI) and non-serious infection (NSI) in non-splenectomized adults treated for persistent or chronic primary ITP, including baseline characteristics, ITP treatments as well as pneumococcal and influenza vaccines. Methods: The population was the 2009-2012 FAITH cohort, which is the cohort of all incident primary ITP adults persistently treated in France built in the national health insurance database (SNIIRAM). The FAITH study is registered ENCePP n°4574. SIs were hospitalizations with infection as primary diagnosis code (predictive positive value: 97%). NSIs were identified using out-hospital antibiotic dispensing. Cox models were performed to assess separately the risk of SIs and of NSIs. The index date was the date of first ITP treatment exposure (date of entry in the FAITH cohort). Follow-up was censored at a first infection, splenectomy, death or end of follow-up (December, 31 2012). The following covariates were included: age, gender, mucosal bleeding at ITP onset, diabetes mellitus, chronic pulmonary, heart and kidney diseases. Exposure to ITP treatments was considered as time-varying covariates. Exposure to rituximab was defined as the 6 months period following dispensing and exposure to vaccine occurring in that period was considered as null. Results: The cohort included 1805 patients. Mean age was 57.6 ± 21.3 years and 58.9% were females. With a mean follow-up of 18.5 ± 6.8 months, 681 patients were exposed to rituximab, 1035 to IVIg, 90 to other immunosuppressants (azathioprine, mycophenolate); 161 (9.1%) patients experienced SIs (39.7% respiratory) and 1227 (68.0%) NSIs. The respective incidences were 6.3/100 patients-years and 8.4/100 patients-months. In multivariate analyses, increasing age and chronic pulmonary disease were associated with both SI and NSI occurrence. Mucosal bleeding at ITP onset, male gender and chronic kidney disease were also associated with SI occurrence. The hazard ratios (HRs) for corticosteroids were 3.83, 95% confidence interval - 95% CI [2.76-5.31] (p

Description: Background: Thrombosis during immune thrombocytopenia (ITP) management is a critical issue. Among suspected risk factors for thrombosis in ITP patients, the role of antiphospholipid antibodies (aPL) is controversial. We performed a systematic review and a meta-analysis to investigate risk of thrombosis with lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2GP1 antibodies in primary ITP. Methods: Literature search was computed on Medline, Cochrane and ISI Web of Sciences by two independent investigators from January 1st 1980 to December 31st 2014. Unpublished studies were searched in meeting abstracts of the American Society of Hematology, the European Haematology Association, the American College of Rheumatology and the European League Against Rheumatism. Inclusion criteria were observational studies including primary ITP patients where presence of aPL was documented (LA, aCL or anti-β2GP1 antibodies). We assessed the occurrence of thrombotic events in these studies. Two investigators performed data extraction. All authors were contacted in order to confirm or provide complementary data if needed. Study quality was assessed using the NewCastle-Ottawa (NOS) scale. The main analysis assessed the risk of all thromboses (arterial or venous) associated with the presence of LA, aCL or anti-β2GP1 antibodies. Sensitivity analyses were performed, restricted to the best quality studies. We also also stratified the risk of arterial and venous thrombosis separately. Random effect (Der Simonian & Laird) models were used. Heterogeneity was assessed using the I2 index. Odds ratio (OR) and their 95% confidence intervals (95%CI) were computed. Publication bias was searched using Egger's test and funnel plot. Results: Searching in electronic databases retrieved 776 citations, completed by 12 additional studies from unpublished literature. Out of them, 44 studies were identified for a full-length text review. Eventually, 10 cohort studies totalizing 1010 patients were selected (9 with LA, 6 with aCL, 2 with anti-β2GP1 antibody dosages). Five studies were prospective and 5 retrospective. The median NOS score was 6 (range: 4-8). The pooled OR for the risk of all thromboses associated with LA positivity was 6.11, 95%CI [3.40-10.99] (I2 =0%, Egger's test: p=0.37). It was 2.13, 95%CI [1.11-4.12] with aCL (I2 =0%, Egger's test: p=0.14). Sensitivity analyses restricted to studies with quality score ≥6 led to similar results. The OR for arterial thrombosis was 5.52, 95%CI [2.40-12.70] with LA and 2.12, 95%CI [0.84-5.33] with aCL. The OR for venous thrombosis was 5.13, 95%CI [2.31-11.40] with LA and 2.00, 95%CI [0.83-4.81] with aCL. Only two studies assessed the risk of thrombosis associated with anti-β2GP1 antibody positivity, with high heterogeneity (I2 =81%). Consequently, no pooled OR was computed. Conclusions: This meta-analysis demonstrates that aPL positivity in ITP patients is a risk factor for thrombosis. The risk was three times higher with LA than with aCL. It was similar for arterial and venous thromboses. For practicing clinicians, our results imply that systematic aPL determinations should be performed in ITP, since aPL positivity and associated thrombosis risk should influence the choice of treatment. Disclosures Michel: Roche: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AMGEN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Godeau:Roche: Research Funding; Amgen: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Description: Background: The incidence ofadverse drug reactions (ADRs) related to immune thrombocytopenia (ITP) drugs is not well known in the real-life practice. Aim: The principal aim of this study was to assess the incidence of ADRs related to ITP drugs. The secondary aims were to compare the incidence of ADRs depending on the drugs, and to assess the factors associated to corticosteroids-related ADR occurrence. Methods: Study population was the patients included between June 2013 and December 2014 in the CARMEN (Cytopénies Auto-immunes: Registre Midi-PyréneEN) 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. It is aimed at the prospective follow-up of all newly diagnosed ITP adults in the French Midi-Pyrénées region (3 million inhabitants). Each investigator prospectively follows every patient newly diagnosed for ITP in routine visit or hospital stay, providing informed consent was received. ITP is defined in accordance with French guidelines: platelet count

Description: Introduction: Population-based studies using health insurance databases are very useful for epidemiological studies, notably for rare diseases such as immune thrombocytopenia (ITP). French health insurance databases, called SNIIRAM (Système d'Information Inter-Régimes de l'Assurance Maladie) cover the entire French population (66 million inhabitants).We developed an algorithm that identifies incident primary ITP cases in the SNIIRAM. The aim of this study was to evaluate the positive predictive value (PPV) of this algorithm. Methods: The SNIIRAM is an electronic database prospectively recording demographic, hospitalization, long term disabling disease (LTD) and out-hospital drugs dispensing as well as other healthcare data. The algorithm used to identify newly diagnosed primary ITP patients follows several steps: 1) extraction of patients with at least one ITP code (D69.3 code of the International Classification of Disease, version 10 -ICD-10) as primary diagnosis during a hospital stay or as LTD; 2) exclusion of patients with ambiguous or contradictory codes, i.e.other D69 ICD-10 codes as LTD or hospital diagnosis between 12 months before and 6 months after the first ITP code, except D69.6 (thrombocytopenia, unspecified) and D69.9 (hemorrhagic condition, unspecified); 3) refining of the presumed date of diagnosis searching ITP drug dispensing in the six-month period before the first ITP code. A six-month wash out period is used to define incident ITP; 4) lastly, secondary ITPs are defined by a LTD or a hospitalization with codes corresponding to hematological malignancies, chronic viral infections and connective tissue diseases between 12 months before and 6 months after the presumed date of diagnosis. For the present validation study, we applied this algorithm to regional SNIIRAM data of the Midi-Pyrénées region (South of France, 3 million inhabitants) to identify incident ITP patients between July 1, 2012 and June 30, 2014. Medical charts were independently reviewed by two investigators. We calculated the PPVs of: 1) the diagnosis of ITP; 2) the fact that ITP was incident or not (compared with the true date of diagnosis and the true date of first ITP symptoms); 3) the identification of secondary ITPs. Results: We identified 200 incident ITP patients in the Midi-Pyrénées regional SNIIRAM during the study period. We could assess by medical chart review 168 cases. At ITP diagnosis, 70.4% of the patients were adults (≥18 years). Median age was 2.8 years in children and 63.0 years in adults. The male:female sex-ratio was 0.83. Overall, 66.6% of the patients had bleeding symptoms. The median platelet count was 10 x 109/L. After medical chart review, 161 cases were true ITP yielding a PPV of 95.8% (95% confidence interval - 95% CI: 92.8-98.8). Among them, 128 were incident according to the date of symptom onset and 134 were incident according to the true diagnosis date yielding PPVs of 79.5% (95% CI: 73.2-85.7) and 83.2% (95% CI: 77.4-89.0), respectively. As expected, the PPV for newly diagnosed ITP was significantly lower in case of low platelet count as first symptom compared tobleeding revealing ITP (respectively, 65.4%, 95% CI: 52.5-78.3 and 92%, 95% CI 86.9-97.0, p=0.08). The median time from the date of first symptoms and the estimated date of ITP onset by the algorithm was 3 days (interquartile range - IQR: 0 to 20). The median time from the true date of diagnosis and the estimated date of ITP diagnosis by the algorithm was 0 days (IQR: 0 to 15). Ten patients were identified as having a secondary ITP using the algorithm: 4 lymphoid neoplasms (2 B-cell lymphoma, 1 Hodgkin lymphoma and 1 chronic lymphoid leukemia), 4 connective tissue diseases (sarcoidosis, rheumatoid arthritis, systemic sclerosis and Sjögren syndrome, 1 case each) and 2 chronic infections (HIV and HCV). There was no misclassification after medical chart review. On the contrary, 7 secondary ITPs identified by medical chart review were not detected by the algorithm: 3 CMV and 1 EBV infections, 1 Waldenström disease, 1 plasmocytoma and 1 myelodysplastic syndrome. Conclusions: This algorithm showed good PPV in identifying incident primary ITP patients and could be extended to other similar databases. The estimated date of ITP onset may be delayed in case of isolated chronic thrombocytopenia because platelet count results are not recorded in the database. The SNIIRAM is not a useful database to detect virus-associated secondary ITP. Disclosures No relevant conflicts of interest to declare.

Description: Background: International guidelines on immune thrombocytopenia (ITP) management recommend vaccination against Streptococcus pneumoniae (S.p.), Haemophilus influenza b (Hib) and Neisseiria meningitidis (N.m.) before splenectomy. French guidelines, published in 2009, state that these vaccines should be administered at least two weeks before splenectomy. They also recommend these vaccinations at least two weeks before rituximab, because 80% of rituximab-treated patients may relapse and may be candidate to splenectomy, while seroconversion is compromised the semester following rituximab. The aim of this study was to assess the application of these recommendations in France. Methods:The study was conducted in the database of the French national health insurance system (SNIIRAM). The French Adult Immune Thrombocytopenia: a French pHarmacoepidemiological study (FAITH, n°ENCEPP/SDPP/4574) is aimed at following in the SNIIRAM the cohort of all incident primary persistent or chronic ITP adult patients treated in France from 2009. The SNIIRAM collects prospectively all data regarding hospitalizations, disabling diseases, drug and procedure reimbursements. They are linkable with demographic data. On the 2009-2011 SNIIRAM data, ITP patients were identified with hospital and disabling disease diagnosis codes (D69.3 code of the International Classification of diseases, version-10 – ICD-10). The date of diagnosis was refined thanks to out-hospital drug exposures. Secondary ITPs were excluded thanks to diagnosis codes of diseases associated to ITP, searched in the year before and the semester after the diagnosis. We restricted to incident patients, excluding those with a diagnosis during the first semester of the study. Lastly, the FAITH cohort includes the patients persistently treated (at least three monthly consecutive dispensing of ITP drug, or exposure to rituximab or splenectomy). Among the 1106 patients of the FAITH cohort identified from July 2009 to June 2011, 427 non-splenectomized patients were exposed to rituximab and 178 underwent splenectomy (67 out of these had been previously exposed to rituximab). We assessed vaccine exposure to S.p., Hib and N.m. and detailed the moment of vaccinations. Vaccination was said “recommended” when it occurs prior to 2 weeks before rituximab or splenectomy. Other indications for vaccination (e.g. chronic pulmonary disease for S.p.vaccine) were searched through disabling diseases and in-hospital diagnosis codes before exposure to rituximab or splenectomy, using validated ICD-10 algorithms. Results: Among the 423 non-splenectomized patients exposed to rituximab, 137 (31.6%) were vaccinated against S.p., 80 (18.9%) against Hib, and 16 (3.8%) against N.m. Only 54 (12.8%) patients benefitted from a recommended vaccination against S.p. A similar pattern of recommended/non-recommended vaccination was observed for Hib and N.m. vaccines. Among the patients vaccinated after the first rituximab infusion, 28.5% (S.p.), 33.7% (Hib) and 37.5% (N.m.) were vaccinated during the 6 months following rituximab, corresponding to the time of maximal B-cell depletion. Forty-one patients (9.7%) had another reason for being vaccinated (mainly heart failure, n=23 and chronic pulmonary disease, n=13). Among them, 6 were vaccinated against S.p., 3 against Hib and none against N.m. Among the 111 splenectomized patients not previously exposed to rituximab, vaccination rates were 52.2% for S.p., 30.6% for Hib and 8.1% for N.m. When vaccinated against S.p., most patients (90.6%) benefitted from a recommended vaccination schedule (80.9% and 81.8% for Hib and N.m. vaccinations, respectively). Among the 67 patients exposed to rituximab before splenectomy, vaccination rates were 64.2% for S.p., 38.8% for Hib and 10.5% for N.m. Among S.p vaccinated patients, 79.6% had a recommended vaccination schedule before splenectomy (70.3% and 77.8% for Hib and N.m. vaccinations, respectively). However, 53.3 % of these recommended vaccinations occurred during the semester following a rituximab infusion (maximal B-cell depletion period). Seven of the 178 splenectomized patients had another reason for being vaccinated. Among them, 4 were vaccinated against S.p. and Hib, and 1 against N.m. Conclusions: Vaccination coverage is low before splenectomy or rituximab in ITP patients in France. Most of the vaccinations are dispensed during a non-recommended period. Disclosures No relevant conflicts of interest to declare.

Description: 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 8 (OR: 7.30; 95% CI [1.36-32.27]) and platelet count

Description: Objectives:The aim of this study was to describe the exposure to corticoid-sparing treatments (CST) in adult primary immune thrombocytopenia (ITP) patients during the year before the chronic phase at a nationwide level in the era of thrombopoietin-receptor agonists (TPO-RAs). Methods:Study population was the 2009-2011 cohort of the French Adult Immune Thrombocytopenia: a French pHarmacoepidemiological study (FAITH, n°ENCEPP/SDPP/4574). The FAITH cohort is the cohort of all incident persistent or chronic adult primary ITP patients treated in France, built through the nationwide French health insurance database, named SNIIRAM. It collects prospectively all data regarding hospitalizations, disabling diseases, drug and procedure reimbursements. They are linkable with demographic data. On the 2009-2011 SNIIRAM data, ITP patients were identified with hospital and disabling disease diagnosis codes (D69.3 code of the International Classification of diseases, version-10). The date of diagnosis was refined thanks to out-hospital drug exposures. Secondary ITPs were excluded thanks to diagnosis codes of diseases associated to ITP, searched in the year before and the semester after the diagnosis. We restricted to incident patients, excluding those with a diagnosis during the first semester of the study, and then to patients followed at least 12 months and with at least one exposure to CST during the year after the diagnosis. Exposure to CST was searched through out-hospital dispensing, and during hospital stays for splenectomy, rituximab and polyvalent intravenous immunoglobulins (IVIg). A single dispensing defined exposure, except for IVIg (3 monthly dispensing were mandatory to differentiate IVIg used as CST from acute exposure to treat a serious bleeding). We described the percentage of patients exposed to the distinct CST at least once during the year after ITP diagnosis and detailed the lines of therapy. We compared the patients aged 10% of the patients at any time during the year after ITP diagnosis were, by decreasing frequency: rituximab (57.8%), splenectomy (22.1%), TPO-RAs (16.8%), IVIg (15.0%), danazol (14.4%) and dapsone (10.8%). Hydroxychloroquine was used in 6.5% of the patients and immunosupressant (azathioprine, mycophenolate or ciclosporin) in 5.9%. The CST the most frequently used was rituximab in both age groups. Splenectomy was more frequently used in patients aged less than 65 years (25.2% versus 16.4%, p=0.03). In contrast, TPO-RAs and dapsone were more frequently used in patients aged over 65 years (respectively, 24.8% versus 12.8%, p=0.01, and 17.6% versus 7.2%, p=0.0008). The mean number of lines of therapy after corticosteroids was 1.5 (extremes: 1-6) and was not different between the two age groups. As regards CSTs used in second line after corticosteroids, rituximab was the most used (45.4%), followed by IVIg (12.0%), splenectomy (11.3%), danazol (10.1%), dapsone (7.9%) and TPO-RAs (6.3%). There were discrepancies according to the age groups: 11.8% of the patients aged ≥65 years had been exposed to TPO-RAs as second-line compared with 3.5% of younger patients (p=0.0006). Similarly, dapsone was more frequently used as second-line treatment in older patients (13.8% versus 5.2%, p=0.0003), while splenectomy was more frequently used in patients aged

Description: Background: Immune thrombocytopenia (ITP) is associated with an increased risk of venous and arterial thrombosis (VT and AT, respectively) as compared with the general population. However, the impact of thrombosis risk factors and of ITP treatments, particularly of thrombopoietin-receptor agonists (TPORAs), is not well known in the routine clinical practice. Aim: The objective of this cohort study was to assess the risk factors of VT and AT in adults with primary ITP, including ITP treatments. Methods: The population was the cohort of all incident primary ITP adults in France during 2009-2015 built within the national health insurance database (French Adult Immune Thrombocytopenia - FAITH - cohort; NCT03429660). Incident ITP patients were identified using a validated algorithm combining drug exposures and diagnosis codes according to the international classification of diseases, version 10 (ICD-10). Risks of first hospitalization with a validated primary discharge diagnosis code of VT and AT (coded with the ICD-10) were assessed separately. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Variables included in multivariable models were: age, sex, history of AT and of VT, diabetes, cardiovascular disease, chronic kidney disease, chronic liver disease, cancer; exposures to antihypertensive, lipid-lowering, antiplatelet, anticoagulant drugs and ITP treatments including splenectomy were modeled as time-dependent variables. Results: The cohort included 7225 adult patient with incident primary ITP: 3807 (52.7%) were ≥60 year-old, 3199 (44.3%) were males, 692 (9.6%) had a history of cardiovascular disease, 937 (13.0%) had diabetes. During the follow-up, 5737 (79.4%) were exposed to corticosteroids, 3364 (46.6%) to intravenous immunoglobulin (IVIg), 995 (13.8%) to TPORAs, and 755 (10.4%) were splenectomized. During the follow-up (23 852 patient-years in total; mean follow-up: 39.5 months), 174 patients had a hospitalization with a primary discharge diagnosis of VT and 333 of AT, leading to incidences of 7.4 (95% CI: 6.4-8.6) and 14.4 (95% CI:12.9-16.0)/1000 patient-years, respectively. In multivariable Cox models, the most important risk factors for VT were higher age (≥60 years vs. 50 year-old, 14 (56.0%) were women, 6 (24.0%) were splenectomized, 9 (36.0%) were concomitantly exposed to corticosteroids and 3 (12.0%) to IVIg; only 3 women aged50 year-old, 15 (71.4%) were men, 8 (38.1%) were splenectomized, 5 (23.8%) were concomitantly exposed to corticosteroids and one to IVIg; only one 48-year-old man had no additional risk factor for AT. Conclusions: Baseline risk factors for VT and AT were highly associated with VT and AT occurrence in adults with primary ITP. Splenectomy, corticosteroids, IVIg and TPORAs were risk factors for VT. Most patients who had a thrombosis while treated by TPORA had additional risk factors. These findings help choosing a tailored treatment strategy for a given patient depending on his/her risk profile for VT and AT. Disclosures Christiansen: Amgen: Research Funding. Bahmanyar:Amgen: Research Funding.

Description: Introduction: The association of measles, mumps and rubella (MMR) vaccination with immune thrombocytopenia (ITP) occurrence has been shown. The risk of ITP with other vaccines is still not known. This study was aimed at assessing the association of recommended vaccinations in children with ITP occurrence. Methods: We conducted a population-based study in France including all children newly diagnosed for primary ITP between July 2009 and June 2015. This cohort was built using a validated algorithm in the nationwide French health insurance database (SNDS). We assessed the risk of ITP with MMR vaccine, all combined vaccines containing diphtheria, tetanus and poliomyelitis (DTP) vaccines, pneumococcal and meningococcal C vaccines. We used two self-controlled designs: a case cross-over and a self-controlled case series. For the case cross-over, we compared the frequency of exposure to vaccines during a 6-week period immediately preceding the event (case period) with the frequency of exposure during a previous time period (control period, having the same duration as the case period). We performed sensitivity analyses using 8- and 12-week periods. Analyses were adjusted for exposure to other drugs known as inducers of ITP and seasonality. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated. For the self-controlled case series, we compared the ITP incidence within periods of risk (following vaccination, named exposure period) with the incidence within the control period of non-exposure. The exposure period was defined by the 6 weeks after the vaccine dispensing in the principal analysis (8 and 12 weeks in sensitivity analyses). We further excluded the 2 weeks prior to vaccine dispensing from the non-exposure period to address selective survival bias (healthy vaccinee effect). The observation period was censored at ITP occurrence, due to variation of vaccination probability after ITP diagnosis and to the impossibility to distinguish ITP relapses from chronic ITP in the database. Analyses were adjusted for seasonality. Incidence rate ratios (IRRs) and their 95% CI were calculated. We assessed the exposure to each vaccine, and conducted subgroup analyses in patients without any concurrent vaccination during case and control periods for the case cross-over study and exposure periods for the self-controlled case series study. We also calculated the number of ITP cases occurring during the 6 weeks after vaccination divided by the number of vaccine doses dispensed in the French children population during the study period. Results: We included 2,549 newly diagnosed primary ITP children. Among them, median age was 5.1 years and 46.5 % were females; 41.4% had been exposed to at least one studied vaccine before ITP onset. The results of the principal analysis are detailed in the Table. There was an increased occurrence of ITP following MMR vaccination (OR: 1.60, 95% CI: 1.09-2.34; IRR: 1.30, 95% CI: 0.95-1.80). Analyses excluding the patients with concurrent vaccination, notably meningococcal vaccination, led to similar results (OR: 1.66, 95% CI: 1.02-2.71; IRR: 1.39, 95% CI: 0.80-2.42). There was also an increased occurrence of ITP with the meningococcal C vaccine (OR: 1.92, 95% CI: 0.95-3.86; IRR: 1.40, 95% CI: 0.86-2.29). Analyses conducted in patients without any concurrent vaccination, notably MMR vaccination, confirmed these results with wide 95% CI because of fewer patients included (OR: 1.64, 95% CI: 0.57-4.71; IRR: 1.64, 95% CI: 0.69-3.86). No association was observed between other vaccines and ITP occurrence. The numbers of ITP cases occurring in the 6 weeks following vaccination per million doses dispensed were 8.2 for pneumococcal, 9.2 for DTP, 9.6 for meningococcal and 11.5 for MMR vaccines. Of note, these numbers overestimate the probability of vaccine-induced ITP. Indeed, they are ITP cases chronologically compatible with vaccine adverse reaction without any individual causality assessment (a worst-case scenario considering that all cases were triggered by vaccines). Conclusion: This study showed an increased occurrence of ITP after MMR and meningococcal C vaccines. It is reassuring for other vaccines. We cannot exclude temporal association with MMR and meningococcal C vaccines due to the peak of ITP incidence at 12 months of age in the general population. However, vaccine-induced ITP is a very rare event, which does not cast doubt on the interest of vaccination. Disclosures No relevant conflicts of interest to declare.