Dear Editor,
Due to an inadvertent omission by the Sponsor (Janssen Scientific Affairs, LLC, Horsham, PA, United States) of preferred terms (PTs) from the Medical Dictionary for Regulatory Activities (MedDRA) in the analyses of non-fatal major adverse cardiovascular events (MACE) from the Psoriasis Longitudinal Assessment and Registry (PSOLAR), the results presented in our article entitled, ‘Evaluation of risk of major adverse cardiovascular events with biologic therapy in patients with psoriasis,’ need to be updated. While initially reviewed annually by the Sponsor via a line-by-line manual assessment of adverse events mapping to the ‘cardiac disorders’ system organ class within MedDRA, the MACE summary process transitioned to a programmed approach early in the registry. During a data review in 2019, it became apparent that some relevant PTs for non-fatal MACE were not included in the programmed process. Specifically, only two general MedDRA PTs (i.e., myocardial infarction and cerebrovascular accident) were included while other relevant PTs (e.g., acute coronary syndrome, acute myocardial infarction, embolic stroke, thrombotic stroke) were omitted unintentionally. As a result, the data tables generated by the Sponsor for review by the authors of the article were incomplete.
When this omission was identified, the Sponsor consulted with cardiovascular and pharmacovigilance experts to determine the appropriate analytical approach to ensure a comprehensive assessment of non-fatal MACE risk. This led to the development of a rigorous search strategy for MACE that captured all PTs included in the Standardized MedDRA Queries of myocardial infarction and ischemic central nervous system vascular conditions. Importantly, the exclusion of non-fatal MACE PTs did not affect the analysis of fatal cardiovascular events, as all adverse events with a reported outcome of death are reviewed along with supporting documentation on a case-by-case basis.
Results of the new analyses showed that unadjusted incidence rates (number/100 patient-years and 95% confidence intervals [CIs]) of non-fatal MACE increased across all PSOLAR cohorts due to the inclusion of additional search terms; however, review of the overall results of the multivariate Cox model analyses (hazard ratios, 95% CIs, and p-values) did not identify any meaningful changes. Specific adjustments are reflected in the following updated tables: (A) Incidence Rates of Major Adverse Cardiovascular Events per 100 Patient-Years (Table 3), (B) Adjusted Hazard Ratios to First Major Adverse Cardiovascular Event (MACE) (Table 4), and (C) Predictors of Major Cardiovascular Event (MACE) Other Than Treatment Effects for the overall population (Table S3), the incident subpopulation (Table S4), and the bionaive subpopulation (Table S5).
It is important to note that the conclusion of the original article remains unchanged - treatment with biologics did not increase the risk of MACE in patients with psoriasis. However, the Sponsor recognizes the importance of this unintended omission and has corrected the process for all future risk assessment pertaining to cardiovascular safety in PSOLAR.
Sincerely,
Robert Bissonnette, MD, Innovaderm Research, Inc., Montreal, Quebec, Canada; and Wayne Langholff, PhD, Janssen Research & Development, LLC, Horsham, PA, United States.
Reference:
1. Bissonnette R, Kerdel F, Naldi L, et al. Evaluation of risk of major adverse cardiovascular events with biologic therapy in patients with psoriasis. J Drugs Dermatol2017;16(10):1002-1013.
Due to an inadvertent omission by the Sponsor (Janssen Scientific Affairs, LLC, Horsham, PA, United States) of preferred terms (PTs) from the Medical Dictionary for Regulatory Activities (MedDRA) in the analyses of non-fatal major adverse cardiovascular events (MACE) from the Psoriasis Longitudinal Assessment and Registry (PSOLAR), the results presented in our article entitled, ‘Evaluation of risk of major adverse cardiovascular events with biologic therapy in patients with psoriasis,’ need to be updated. While initially reviewed annually by the Sponsor via a line-by-line manual assessment of adverse events mapping to the ‘cardiac disorders’ system organ class within MedDRA, the MACE summary process transitioned to a programmed approach early in the registry. During a data review in 2019, it became apparent that some relevant PTs for non-fatal MACE were not included in the programmed process. Specifically, only two general MedDRA PTs (i.e., myocardial infarction and cerebrovascular accident) were included while other relevant PTs (e.g., acute coronary syndrome, acute myocardial infarction, embolic stroke, thrombotic stroke) were omitted unintentionally. As a result, the data tables generated by the Sponsor for review by the authors of the article were incomplete.
When this omission was identified, the Sponsor consulted with cardiovascular and pharmacovigilance experts to determine the appropriate analytical approach to ensure a comprehensive assessment of non-fatal MACE risk. This led to the development of a rigorous search strategy for MACE that captured all PTs included in the Standardized MedDRA Queries of myocardial infarction and ischemic central nervous system vascular conditions. Importantly, the exclusion of non-fatal MACE PTs did not affect the analysis of fatal cardiovascular events, as all adverse events with a reported outcome of death are reviewed along with supporting documentation on a case-by-case basis.
Results of the new analyses showed that unadjusted incidence rates (number/100 patient-years and 95% confidence intervals [CIs]) of non-fatal MACE increased across all PSOLAR cohorts due to the inclusion of additional search terms; however, review of the overall results of the multivariate Cox model analyses (hazard ratios, 95% CIs, and p-values) did not identify any meaningful changes. Specific adjustments are reflected in the following updated tables: (A) Incidence Rates of Major Adverse Cardiovascular Events per 100 Patient-Years (Table 3), (B) Adjusted Hazard Ratios to First Major Adverse Cardiovascular Event (MACE) (Table 4), and (C) Predictors of Major Cardiovascular Event (MACE) Other Than Treatment Effects for the overall population (Table S3), the incident subpopulation (Table S4), and the bionaive subpopulation (Table S5).
It is important to note that the conclusion of the original article remains unchanged - treatment with biologics did not increase the risk of MACE in patients with psoriasis. However, the Sponsor recognizes the importance of this unintended omission and has corrected the process for all future risk assessment pertaining to cardiovascular safety in PSOLAR.
Sincerely,
Robert Bissonnette, MD, Innovaderm Research, Inc., Montreal, Quebec, Canada; and Wayne Langholff, PhD, Janssen Research & Development, LLC, Horsham, PA, United States.
Reference:
1. Bissonnette R, Kerdel F, Naldi L, et al. Evaluation of risk of major adverse cardiovascular events with biologic therapy in patients with psoriasis. J Drugs Dermatol2017;16(10):1002-1013.
