Background: High dose glucocorticoids are recommended as initial treatment for adults with Immune primary thrombocytopenia (ITP). In the majority of patients (85%), dexamethasone is effective at increasing platelet counts, but within 6 months 50% will relapse. Romiplostim is a peptibody designed to activate the TPO receptor, leading to platelet responses in 79-95% of ITP patients as second line treatment. There is accumulating evidence that the combination of immunosuppressive drugs and TPO analogues (TPOa) may improve ITP responses. Aims: Primary objective To evaluate the superiority of romiplostim plus dexamethasone vs dexamethasone alone in patients with newly primary immune thrombocytopenia (ITP) in terms of sustained response off any ITP treatment and without WHO grade 2 or more bleeding Secondary objectives • To compare the efficacy of dexamethasone plus romiplostim vs dexamethasone in terms of complete response (CR), response (R), global response (GR), SR at 6 and 12 months and other efficacy-related endpoints • Safety and tolerability • Quality of life • Cost-effectiveness analysis comparing dexamethasone plus romiplostim vs dexamethasone (Health-resource utilization, HRU) Methods: This is an open label, randomized (1:1), phase 3 study designed to compare romiplostim plus dexamethasone vs dexamethasone alone (See figure 1). 126 patients will be enrolled in 30 study sites from Spain, United Kingdom and Italy. • Arm 1 (Romiplostim plus dexamethasone): dexamethasone 40 mg daily for 4 days only in the first cycle and subcutaneous romiplostim weekly for up to 12 months (ROM + DEX arm). Romiplostim will be tapered when platelets are ≥ 50x109/L for more than 4 weeks (see figure 2). • Arm 2 (Dexamethasone): dexamethasone 40 mg daily for 4 days for up to 3 cycles every 14 to 28 days (DEX arm). Results: Patients will be followed for a minimum of 12 months from randomization and a minimum of 6 months after discontinuing treatment with either romiplostim or dexamethasone. The following assessments will be done in these visits: platelets count, bleeding score (ITP-BAT, WHO criteria), number and characteristics of bleeds, adverse events (CTCAE version 4.03), study medication, rescue medication and concomitant medication, HRU associated with the ITP or its treatment and loss of productivity and quality of life (EQ-5D, 36-Item Short-Form Health Survey (SF-36) version 2, Investigating Choice Experiments Capability Measure–Adults (ICECAP-A) questionnaire, version 2; fatigue as measured on the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) scale, version 4). Intravenous immunoglobulins (IVIg), platelet transfusion or prednisone will be considered rescue treatment. Treatment failure definitions: • In the ROM + DEX arm, treatment failure is defined as a platelet count <30x109/L after 4 weeks of romiplostim at 10 mcg/kg/week or if rescue medication is needed to get this level of platelets despite romiplostim 10mcg/kg/week for 4 weeks. • In DEX arm, treatment failure is defined as a platelet count <30x109/L after 3 cycles of dexamethasone or if rescue medication is needed to get this level of platelets despite the 3 cycles of dexamethasone. Image:Summary/Conclusion: This study will evaluate dexamethasone and romiplostim combination in comparison to dexamethasone alone for first line ITP treatment in terms of response, sustained response off any ITP treatment (SROT), bleeding, adverse events, need for rescue treatments and quality of life.

Emicizumab is a bispecific antibody that activates FX to FXa in the absence of FVIII. It has been shown to reduce bleeding episodes in people with haemophilia A complicated by a FVIII inhibitor. Despite the protection against bleeds, some breakthrough bleeds are inevitable and these may require additional haemostatic treatment. Emicizumab has been associated with severe adverse events when co-administered with activated prothrombin complex concentrate. To minimize the risk of adverse events, the UK Haemophilia Centre Doctors' Organisation issues the following updated interim guidance to its Inhibitor Guidelines for managing patients receiving Emicizumab based on the limit published information available in February 2018.

1Arthur Bloom Haemophilia Centre, University Hospital of Wales, Cardiff, UK 2Haemophilia Centre, Royal Hospital for Children, Glasgow, UK 3Haemophilia Centre, Evelina London Children’s Hospital, London, UK 4Haemophilia Centre, University Departmentt of Haematology, Manchester, UK 5Haemophilia Centre, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK 6Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, UK 7Departement of Haematology, Sheffield Children’s Hospital, Sheffield, UK 8Haemophilia Centre, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK 9Haemophilia Centre, Department of Paediatric Haematology, Leeds Children’s Hospital, Leeds, UK 10Haemophilia Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust (NUTH), Newcastle, UK 11Department of Paediatric Haematology, Bristol Royal Hospital for Children, Bristol, UK 12Department of Haematology, Birmingham Children’s Hospital, Birmingham, UK 13Barts and The London School of Medicine & Dentistry, QMUL, London, UK

HaemophiliaVolume 21, Issue 1 p. e73-e76 Letter to the Editor A national survey of immunosuppression strategies for acquired haemophilia A P. Batty, P. Batty The Royal London Hospital Haemophilia Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UKSearch for more papers by this authorB. Palmer, B. Palmer The National Haemophilia Database, Manchester, UKSearch for more papers by this authorE. Chalmers, E. Chalmers Royal Hospital for Sick Children, Glasgow, UKSearch for more papers by this authorC. R. M. Hay, C. R. M. Hay Manchester University Department of Haematology, Manchester Royal Infirmary, Manchester, UKSearch for more papers by this authorR. Liesner, R. Liesner Great Ormond Street NHS Trust, London, UKSearch for more papers by this authorS. Rangarajan, S. Rangarajan Hampshire Hospital NHS Foundation Trust, Basingstoke & North Hampshire Hospital, Basingstoke, UKSearch for more papers by this authorK. Talks, K. Talks Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle, UKSearch for more papers by this authorM. Williams, M. Williams Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UKSearch for more papers by this authorP. Collins, P. Collins School of Medicine, Cardiff University, University Hospital of Wales, Cardiff, UKSearch for more papers by this authorD. P. Hart, Corresponding Author D. P. Hart The Royal London Hospital Haemophilia Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK Correspondence: Daniel P. Hart, The Royal London Hospital Haemophilia Centre, Haematology Day Unit, The Royal London Hospital, Whitechapel, E1 1BB London, UK. Tel.: 0203 594 1869; fax: 0203 594 1859; e-mail: daniel.hart@bartshealth.nhs.ukSearch for more papers by this author P. Batty, P. Batty The Royal London Hospital Haemophilia Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UKSearch for more papers by this authorB. Palmer, B. Palmer The National Haemophilia Database, Manchester, UKSearch for more papers by this authorE. Chalmers, E. Chalmers Royal Hospital for Sick Children, Glasgow, UKSearch for more papers by this authorC. R. M. Hay, C. R. M. Hay Manchester University Department of Haematology, Manchester Royal Infirmary, Manchester, UKSearch for more papers by this authorR. Liesner, R. Liesner Great Ormond Street NHS Trust, London, UKSearch for more papers by this authorS. Rangarajan, S. Rangarajan Hampshire Hospital NHS Foundation Trust, Basingstoke & North Hampshire Hospital, Basingstoke, UKSearch for more papers by this authorK. Talks, K. Talks Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle, UKSearch for more papers by this authorM. Williams, M. Williams Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UKSearch for more papers by this authorP. Collins, P. Collins School of Medicine, Cardiff University, University Hospital of Wales, Cardiff, UKSearch for more papers by this authorD. P. Hart, Corresponding Author D. P. Hart The Royal London Hospital Haemophilia Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK Correspondence: Daniel P. Hart, The Royal London Hospital Haemophilia Centre, Haematology Day Unit, The Royal London Hospital, Whitechapel, E1 1BB London, UK. Tel.: 0203 594 1869; fax: 0203 594 1859; e-mail: daniel.hart@bartshealth.nhs.ukSearch for more papers by this author First published: 24 November 2014 https://doi.org/10.1111/hae.12547Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume21, Issue1January 2015Pages e73-e76 RelatedInformation

Although it has been suggested that switching of factor VIII (FVIII) products may increase inhibitor formation this is disputed. Half of UK patients changed rFVIII brands because of national contracting in 2010, presenting an opportunity to compare inhibitor incidence of switchers with non-switchers. Centres were requested to test all the patients for inhibitors prior to the switching date and 6-monthly thereafter. Positive and negative inhibitor test data were also collected to analyse for testing bias. A total of 1198 patients with severe haemophilia A and treated with Advate, Kogenate/Helixate or Refacto AF preswitch were included in the analysis, of whom 516 switched to Refacto-AF and 682 did not switch products. Five new inhibitors were reported amongst previously treated patients (>50 exposure days) with a median titre at the time of detection of 1.25BUmL(-1) (IQR 0.7-23.05). One inhibitor occurred in a non-switcher using Kogenate, an incidence of 1.5 per 1000 treatment-years (95% CI 0.2-10.5). Four inhibitors arose in patients who had switched from Kogenate (two) or Advate (two) to ReFacto-AF, an incidence of 7.8 per 1000 treatment-years (95% CI 2.9-20.8). These incidence rates did not differ significantly from one another (incidence rate ratio 5.3 (95% CI 0.5-260.3) or from the historical rate of 6.05 inhibitors/1000 treatment-years (95% CI 5.18-7.06). Only one inhibitor (non-switcher) persisted. Non-switchers were significantly older (P= 0.03), and used significantly less FVIII per year (P= 0.005) prior to switching. Following switching, factor usage increased similarly (P=0.53) in both groups. Switching from FLRFVIII to Refacto-AF (BDDRFVIII) was not associated with an increased inhibitor development.