Combining thrombopoietin receptor agonists with immunosuppressive drugs in adult patients with multirefractory immune thrombocytopenia, an update on the French experience.

Combining drugs could be an effective option for treating multirefractory ITP, that is, patients not responding to rituximab, thrombopoietin receptor agonists (TPO-RA) and splenectomy. We conducted a retrospective, multicenter, observational study including multirefractory ITP patients who received a combination of a TPO-RA and an immunosuppressive drug. We included 39 patients (67% women, median age 59 years [range 21-96]), with a median ITP duration of 57 months [3-393] and a median platelet count at initiation of 10 × 109 /L [1-35]. The combination regimen was given for a median duration of 12 months [1-103] and included eltrombopag (51%) or romiplostim (49%), associated with mycophenolate mofetil (54%), azathioprine (36%), cyclophosphamide (5%), cyclosporin (3%) or everolimus (3%). Overall, 30 patients (77%) achieved at least a response (platelet count ≥30 × 109 /L and at least doubling baseline during at least 3 months), including 24 complete responses (platelet count >100 × 109 /L during at least 3 months) with a median time to response of 30 days [7-270] and a median duration of response of 15 months [4-63]. Severe adverse event related to ITP treatment was observed in 31%. In conclusion, this study confirms that some patients with multirefractory ITP can achieve long lasting response with this combination.

Characterisation of a high-risk profile for maternal thrombotic and severe haemorrhagic complications in pregnant women with antiphospholipid syndrome in France (GR2): a multicentre, prospective, observational study.

BACKGROUND: Prospective data about the risks of thrombotic and severe haemorrhagic complications during pregnancy and post partum are unavailable for women with antiphospholipid syndrome. We aimed to assess thrombotic and haemorrhagic events in a prospective cohort of pregnant women with antiphospholipid syndrome. METHODS: This multicentre, prospective, observational study was done at 76 centres in France. To be eligible for this study, women had to have diagnosis of antiphospholipid syndrome; have conceived before April 17, 2020; have an ongoing pregnancy that had reached 12 weeks of gestation; and be included in the study before 18 weeks of gestation. Exclusion criteria were active systemic lupus erythematosus nephropathy, or a multifetal pregnancy. Severe haemorrhage was defined as the need for red blood cell transfusion or maternal intensive care unit admission because of bleeding or invasive procedures, defined as interventional radiology or surgery, to control bleeding. The GR2 study is registered with ClinicalTrials.gov, NCT02450396. FINDINGS: Between May 26, 2014, and April 17, 2020, 168 pregnancies in 27 centres met the inclusion criteria for the study. 89 (53%) of 168 women had a history of thrombosis. The median term at inclusion was 8 weeks gestation. 16 (10%) of 168 women (95%CI 5-15) had a thrombotic (six [4%] women; 95% CI 1-8) or severe haemorrhagic event (12 [7%] women; 95% CI 4-12). There were no deaths during the study. The main risk factors for thrombotic events were lupus anticoagulant positivity at inclusion (six [100%] of six women with thrombosis vs 78 [51%] of 152 of those with no thrombosis; p=0·030) and placental insufficiency (four [67%] of six women vs 28 [17%] of 162 women; p=0·013). The main risk factors for severe haemorrhagic events were pre-existing maternal hypertension (four [33%] of 12 women vs 11 [7%] of 156 women; p=0·014), lupus anticoagulant positivity at inclusion (12 [100%] of 12 women vs 72 [49%] of 146 women; p<0·0001) and during antiphospholipid history (12 [100%] of 12 women vs 104 [67%] of 156 women; p=0·019), triple antiphospholipid antibody positivity (eight [67%] of 12 women vs 36 [24%] of 147 women; p=0·0040), placental insufficiency (five [42%] of 12 women vs 27 [17%] of 156 women; p=0·038), and preterm delivery at 34 weeks or earlier (five [45%] of 11 women vs 12 [8%] of 145 women; p=0·0030). INTERPRETATION: Despite treatment adhering to international recommendations, a proportion of women with antiphospholipid syndrome developed a thrombotic or severe haemorrhagic complication related to pregnancy, most frequently in the post-partum period. Lupus anticoagulant and placental insufficiency were risk factors for these life-threatening complications. These complications are difficult to prevent, but knowledge of the antenatal characteristics associated with them should increase awareness and help physicians manage these high-risk pregnancies. FUNDING: Lupus France, association des Sclérodermiques de France, association Gougerot Sjögren, Association Francophone contre la Polychondrite chronique atrophiante, AFM-Telethon, the French Society of Internal Medicine and Rheumatology, Cochin Hospital, the French Health Ministry, FOREUM, the Association Prix Veronique Roualet, and UCB.

Bone marrow biopsy diagnostic yield in internal medicine.

BACKGROUND: Trephine bone marrow biopsy (BMB) in internal medicine has only been studied in fever of unknown origin and inflammation of unknown origin. The aim was to assess BMB diagnostic yield according to main indications and patient characteristics in internal medicine. Quality of BMB and contribution of bone marrow aspiration (BMA) to BMB were also analyzed. METHODS: BMB performed in the internal medicine department of Poitiers university hospital between January 2000 and December 2015 were retrospectively analyzed. Patient characteristics, BMB indications, quality parameters, and results were collected from medical records. Contributive BMB was BMB allowing accurate final diagnosis. Diagnostic yield was the proportion of contributive BMB among total BMB performed. RESULTS: A total of 468 BMBs conducted for primary diagnostic purpose from 468 patients were analyzed. Cytopenia(s) and the indication 'adenopathy and/or splenomegaly and/or hepatomegaly' represented 70% of the indications. Overall BMB diagnostic yield was 32.7%, lymphoma being the main histologic finding (31%). Among indications, cytopenia(s) had the highest diagnostic yield (49.1%). Isolated fever of unknown origin had low diagnostic yield (5.6%). Factors independently associated with contributive BMB were: anemia, neutropenia, circulating immature granulocytes or blasts, monoclonal gammopathy, period of BMB processing, quality of BMB, and immunohistochemestry (IHC) analysis. Concomitant BMA improved diagnostic yield by 5.5%, mostly for myelodysplastic syndromes. CONCLUSION: Cytopenia(s), blood cythemias and monoclonal gammopathy are indications with the highest diagnostic yield. Concomitant BMA and IHC analysis should be systematically performed to increase BMB diagnostic yield in internal medicine.

Large-vessel vasculitis diagnosed between 50 and 60 years: Case-control study based on 183 cases and 183 controls aged over 60 years.

BACKGROUND: Age at onset of large-vessel vasculitis (LVV) is commonly used to distinguish giant cell arteritis (GCA) and Takayasu arteritis (TA). However, LVV between age 50 and 60 years may be difficult to classify. METHODS: We conducted a retrospective study including LVV aged between 50 and 60 years at onset (LVV50-60, cases) and compared them to LVV aged over 60 years (LVV>60, controls). LVV was defined histologically and/or morphologically. Controls fulfilled ACR 1990 criteria for GCA or presented isolated aortitis. RESULTS: We included 183 LVV50-60 and 183 gender-matched LVV>60. LVV50-60 had more frequent peripheral limb manifestations (23 vs. 5%), and less frequent cephalic (73 vs. 90%) and ocular signs (17 vs. 27%) than LVV>60. Compared to LVV>60, CT angiography and PET/CT scan were more frequently abnormal in LVV50-60 (74 vs. 38%, and 90 vs. 72%, respectively), with aorta being more frequently involved (78 vs. 47%). By multivariate analysis, absence of cephalic symptoms, presence of peripheral limb ischemia and aorta involvement, and increased CRP level were significantly associated with LVV50-60 presentation compared to LVV>60. At last follow-up, compared to LVV>60, LVV50-60 received significantly more lines of treatment (2 vs. 1), more frequent biologics (12 vs. 3%), had more surgery (10 vs. 0%), and had higher prednisone dose (8.8 vs. 6.5 mg/d) at last follow-up, CONCLUSION: LVV onset between 50 and 60 years identifies a subset of patients with more frequent aorta and peripheral vascular involvement and more refractory disease compared to patients with LVV onset after 60.