The risk of hepatic adverse events of systemic medications for psoriasis: a prospective cohort study using the BIOBADADERM registry

Abstract

Background

Limited information is available regarding the risk of incident liver disease in patients with psoriasis receiving systemic therapies.

Objectives

To describe the liver safety findings of conventional and modern systemic therapies for moderate-to-severe psoriasis, and to compare the relative incidence rates of hepatic adverse events (AEs) for each drug.

Methods

All the patients on the BIOBADADERM registry were included. Crude and adjusted incidence rate ratios (cIRR and aIRR, respectively) of hepatic AEs, using anti-TNF drugs as reference, were determined. Outcomes of interest were hypertransaminasemia, nonalcoholic fatty liver disease (NADFLD) and a group of other, less represented, hepatic AEs.

Results

Our study included 3,171 patients exposed to systemic drugs (6279 treatment cycles). Incident hypertransaminasemia was the most frequent hepatic AE (incidence rate of 21 per 1000 patients-years [CI 95% 18–23]), followed by NAFLD (8 cases per 1000 patients-years [95% CI 6–10]). Methotrexate (aIRR 3.06 [2.31–4.4]; p = 0.000) and cyclosporine (aIRR 2.37 [1.05–5.35]; p = .0378) were associated with an increased risk for hypertransaminasemia when compared to anti-TNF-α agents. No differences were observed between different groups of biologics. Conventional therapies were not associated with new incident NAFLD.

Conclusions

Comparative information of the incidence of hepatic AEs could facilitate drug selection in moderate-to-severe psoriasis.

Keywords:

• Psoriasis
• risk
• psoriasis treatment
• liver
• hepatic
• adverse event

Acknowledgements

This work was conducted within the BIOBADADERM Study Group. The following members participated in acquisition of data and review of the manuscript: Cristina Santamaría (Hospital Universitario de la Princesa); Blanca Madrid Álvarez (Hospital Universitario de Gran Canaria Dr. Negrín); M^a del Mar Onteniente Gomis, Diana Batista Cabrera (Hospital Universitario 12 de Octubre); Carlos Ferrándiz (Hospital Universitari Germans Trias i Pujol); Patricia Molina Mejías (Hospital Universitario Infanta Leonor); Carlos García Giner, Alfred Perez (Hospital General Universitario de Alicante); Eliseo Martínez-García, Cristina Sánchez (Hospital Universitario Virgen de la Victoria); Elena García Zamora (Fundación Hospital de Alcorcón); Sara Pedregosa Fauste (Hospital Clinic de Barcelona); Desiree Molina (Hospital General Universitario Gregorio Marañón); José Luis Sánchez-Carazo (Hospital General Universitario de Valencia); Rafael Botella-Estrada, Natalia Chaparro Aguilera, Verónica Massó López (Hospital Universitario La Fe de Valencia); Lourdes Rodríguez Fernández-Freire (Hospital Universitario Virgen del Rocío de Sevilla); Almudena Mateu Puchades, Sergio Santos, Marina Sáez Belló (Hospital Universitario Dr. Peset), Ángeles Flórez Menéndez, Laura Salgado, Beatriz González Sixto, M^a Teresa Abalde, Lucia Vilanova, Alexandra Perez Mariño (Complexo Hospitalario Universitario de Pontevedra); Noemí Eiris, Vicenta Prieto Marcos (Complejo Asistencial Universitario de León); Marina de Vega Martínez (Fundación Piel Sana AEDV).

Disclosure statement

Dr. Munera-Campos has participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including Abbvie, Almirall, Celgene, Janssen, LEO Pharma, Lilly, Novartis and Pfizer and has received travel grants for congresses from Novartis and Lilly, and educational grants from Lilly.

Dr Vilar-Alejo participated as AB from Janssen, Novartis, AbbVie, Almirall and Celgene.

Dr Rivera acted as consultant and/or speaker for and/or participated in clinical trials as IP for Abbvie, Almirall, Celgene, Janssen, Leo Pharma, Lilly, Novartis, MSD and Pfizer-Wyeth.

Dr. Carrascosa has participated as a speaker and/or advisor and/or PI/SI clinical trials sponsored by for Celgene, Janssen, Lilly, Leo Pharma, Novartis, Pfizer, MSD, Biogen, Mylan, Amgen and Abbvie, Sandoz.

Dr Dauden acted as consultant for Abbott, Amgen, Astellas, Centocor Ortho Biotech Inc, Galderma, Glaxo, Jansenn-Cilag, Leo Pharma, Novartis, Pfizer, MSD and Celgene, received honoraria form Abbott, Amgen, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, MSD, Celgene, participated in a speakers bureau for Abbott, Pfizer, MSD and Janssen and received grants from Pfizer, Abbott, Janssen and MSD.

Dr Herrera-Acosta has served as consultant and/or speaker with Leo Pharma, Novartis, Janssen, Lilly, Celgene y Abbvie.

Dr Sahuquillo has served as a consultant and/or paid speaker for and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Novartis and Pfizer.

Dr Baniandrés-Rodríguez acted as a consultant and/or speaker for Janssen-Cilag, AbbVie, Pfizer, Novartis, Lilly, Celgene, Leo Pharma and Almirall.

Dr de la Cueva acted as a consultant and/or speaker for Janssen-Cilag, AbbVie, MSD, Pfizer, Novartis, Lilly, Almirall, UCB, Biogen, Celgene, Amgen, Sandoz, Sanofi and Leo-Pharma.

Dr López-Estebaranz participated as AB and received educational grants from Janssen, Abbvie, MSD, Lilly, Novartis, LeoPharma, Pfizer.

Dr Belinchón acted as a consultant and/or speaker for and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including Janssen Pharmaceuticals Inc, Almirall SA, Lilly, AbbVie, Novartis, Celgene, Biogen Amgen, Leo-Pharma, UCB, Pfizer-Wyeth, and MSD.

Dr Ferran has participated as speaker and/or advisor for Janssen, Lilly, Novartis, Pfizer, MSD, Abbvie, Amgen, Celgene, Leo-Pharma and Almirall.

Dr Riera-Monroig received travel grants for congresses from Abbvie, Almirall, Janssen, LEO-Pharma, Novartis.

Dr Rodriguez Fernandez-Freire acted as a consultant and speaker for Janssen-Cilag, AbbVie, MSD, Pfizer, Novartis, Lilly, Almirall, Celgene and Leo-Pharma.

Dr Carretero has been reimbursed by Janssen, Abbvie, Novartis, Pfizer, MSD and Celgene for advisory service and conference.

Dr García-Donoso participated as AB from AbbVie, Almirall and speaker for Janssen, Lilly and Celgene.

Dr Llamas-Velasco acted as a consultant and speaker and participated in clinical trials for AbbVie, Amgen, Almirall, Celgene, Leo-Pharma, Pfizer, Novartis, Lilly, UCB.

Dr Herrera-Ceballos has served as a consultant and/or speaker for and/or participated in clinical trials as IP and sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Janssen-Cilag, LEO Pharma, Lilly, Novartis and Pfizer.

Dr Pujol-Marco has served as a consultant and/or paid speaker for and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Novartis and Pfizer.

Dr Ruiz-Genao has been reimbursed by Pfizer, Janssen, Celgene, Abbvie, Novartis and LeoPharma for advisory services and conferences.

Dr Alsina gave expert testimony for Merck-Schering Plow, Pfizer, Janssen, Novartis, Lilly and Abbott, and has participated as speaker for Almirall, Janssen and Gebro Pharma.

Dr Garcia-Doval received travel grants for congresses from Abbvie, MSD and Pfizer.

None of the other authors has any conflicting interests to declare.

IRB status: Observational study. Approved (Biobadaderm: Hospital Universitario 12 de Octubre (216/07)

References

Additional information

Funding

The BIOBADADERM project is promoted by the Fundación Piel Sana Academia Española de Dermatología y Venereología, which receives financial support from the Spanish Medicines and Health Products Agency (Agencia Española de Medicamentos y Productos Sanitarios) and from pharmaceutical companies (Abbott/Abbvie, Almirall, Amgen, Janssen, Novartis and UCB). The following companies have also collaborated in the past (Leo Pharma, Lilly, MSD and Pfizer). Collaborating pharmaceutical companies were not involved in the design and conduct of the study; collection, management, analysis and interpretation of data; preparation, review, or approval of the manuscript; decision to submit the manuscript for publication.