New haemophilia guidelines out despite low evidence base


By Mardi Chapman

8 Jul 2024

New ISTH haemophilia guidelines have recommended prophylaxis with either emicizumab or factor VIII concentrates for moderately severe haemophilia A without inhibitors after public consultation led to a rare change from the draft recommendation favouring emicizumab. 

Speaking at ISTH 2024 Congress in Bangkok, Professor Suely Rezende said about a third of the 500 comments from researchers, industry, and patient organisations across 22 countries related to the recommendation. 

“We know that it’s very uncommon to change a recommendation after public comments, but the panel understood that we should discuss this recommendation further, and then it changed from suggesting prophylaxis with emicizumab over prophylaxis with factor VIII to suggest either prophylaxis with emicizumab or prophylaxis with factor VIII,” she said.

“This modification was based on a suggested mild effect favouring emicizumab over factor VIII concentrates in bleeding prevention… and the other things that the panel considered were the question about long term safety issues or long term follow up with emicizumab, and also because it was the result of an indirect comparison.”

The final recommendation notes that emicizumab may offer a lower treatment burden for patients.

Professor Rezende, from the Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, told the meeting that the guidelines were unfortunately mostly based on low or very low certainty evidence.

Only two of the 13 recommendations, recommendations 1 and 12 for prophylaxis over episodic treatment of bleeding events for severe and moderately severe haemophilia A and and B respectively, were considered strong based on moderate certainty of the evidence.

“All the others were conditional recommendations based on low or very low certainty in the evidence for the remaining questions, which were 85% of the guideline.”

She said another limitation of the guidelines was that they did not consider therapies approved after 2021 such as efanesoctocog alfa, concizumab and the gene therapy products  valoctocogene roxaparvovec and etranacogene dezaparvovec.

“The next versions of the ISTH haemophilia guidelines will include the technologies such as non-factor or rebalancing therapies, gene therapy and novel factor concentrates. It will appraise other relevant outcomes, if we have these available in the literature, such as health-related quality of life, joint impairment, joint pain, treatment adherence, factor levels and trough levels etc. and include non-severe haemophilia.”

Professor Rezende said the ISTH guidelines were largely consistent with others from ASH and the World Federation of Haemophilia (WFH).

She encouraged delegates to read the guidelines in full and the three linked articles, all published in the Journal of Thrombosis and Haemostasis [link to guideline here

An accompanying Commentary [link here] said ISTH chose the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to evaluate and rank the strength of the recommendations.

However GRADE emphasises higher-quality evidence obtained in randomised trials.

“In rare diseases such as HA and B, randomised studies are seldom performed. It is therefore not surprising that the only recommendation released with strong evidence by the ISTH guidelines pertains to prophylaxis for both severe and moderately severe HA and haemophilia B,” it said.

The ISTH Congress also discussed global recommendations for the treatment of thrombotic thrombocytopenic purpura and guidance  on the evaluation, analysis, and reporting of medication adherence for clinical trials of anticoagulants in children.

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