Chapter 6 118 TA667 Caplacizumab with plasma exchange and immunosuppression for treating acute acquired thrombotic thrombocytopenic purpura In 2020, NICE assessed the cost-effectiveness of the humanized antibody caplacizumab, used together with plasma exchange and immunosuppression for the treatment of acute acquired thrombotic thrombocytopenic (TTP) purpura. Caplacizumab inhibits the interaction between VonWillebrand-factor and thrombocytes, thereby reducing the aggregation of thrombocytes which is typical for TTP. Sanofi was the submitting Company and the Peninsula Technology Assessment Group (PenTAG) produced the evidence review group (ERG) report. In the main trial for caplacizumab (HERCULES, N=145), no patient died while on treatment with caplacizumab (0%). Due to the unreliability of mortality data from the trial (clinicians noted that mortality was unlikely to be 0%), data from the compassionate use programme was brought in. At the first data lock, eight out of 187 (4.2%) of the patients perished, and 9/239 (3.8%) at second data lock. The limited information available rendered the interpretation of these data difficult. Mortality from the compassionate use programme was based on deaths reported via Adverse Event Reporting. No baseline characteristics were available to compare patients among data sources: The monitoring programme for caplacizumab was a compassionate use programme rather than a data collection programme. As such, the only information available includes where the patient was from, whether caplacizumab was received and whether the patient died, (…). Therefore, an assessment of the similarity between mortality sources using patient characteristics could not be conducted. Therefore, the ERG ‘notes potential ambiguities and sources of bias in the compassionate use program (…) including unknown follow-up periods, unclear recruitment process, and that it draws from an international population.’ The company interjected that ‘the compassionate use programme estimates selected to represent caplacizumab in the comparison are, if anything, too high’ – as ‘clinicians agreed that treatment with caplacizumab is started later in the compassionate use programme that it would be if it was made available through routine funding (as requests are individual and caplacizumab is not available on site). Mortality data based on this programme should therefore be considered as the maximum mortality expected with caplacizumab.’ The committee agreed that it was impossible to ‘estimate reliably the extent of the benefit using the randomised trial data’ and recognized the need for use of data on deaths from the global compassionate use scheme. It noted that the absolute rate of death for people treated with caplacizumab under the compassionate use scheme was likely to be valid, but that the relative benefit ascribed to caplacizumab from observational data ‘was very likely to be confounded’.
RkJQdWJsaXNoZXIy MTk4NDMw