Available online 9 December 2023, 152341

Author links open overlay panel, , , , , , , , , , ABSTRACTObjective

to investigate the occurrence and relative risk of incident malignancy in patients with rheumatic diseases and previous malignancies treated with biologic and targeted synthetic DMARDs (b/tsDMARDs).

Methods

Cohort study of patients included in BIOBADASER 3.0 up to 2021, treated with b/tsDMARDs and history of a previous malignancy. Incident cancer was defined as any cancer (new primary, local recurrence or metastases) during the drug exposure. Incidence rate ratios of cancer per 1,000 patients-year (PY) and 95% confidence interval (CI) were estimated. Rates of incident cancer in tsDMARDs and other bDMARDs versus TNFi were compared.

Results

A total of 352 patients from over 9,129 patients recorded in BIOBADASER 3.0 had a history of a previous malignancy. Overall, there were 47 incident malignancies (28 solid cancers, 18 non-melanoma skin cancers and 1 melanoma). The overall rate of incident malignancy was 47.4 (95% CI 35.6-63.1) events/1,000 PY, ranging between 24.5 events/1000 PY in the anti-CD20 group to 93 events/1000 PY in the anti-CTLA-4 group. We did not find differences in the adjusted rate of incident cancer in patients exposed to JAKi [0.5 (95% CI 0.2-1.7)], anti-CD20 [0.4(95% CI 0.1-1)], or anti-IL6 [1.1(95% CI 0.5-2.4)], anti-CTLA-4 [1.5 (95% CI 0.7-3.1) or anti-IL17 [0.7 (95% CI 0.2-2.4) versus versus TNFi therapy.

Conclusions

We did not find differences in the risk of incident cancer in patients with rheumatic diseases and a previous malignancy between TNFi and other b/tsDMARDs. While incident cancers in our cohort were limited, our data is reassuring, awaiting validation in future studies.

Section snippetsINTRODUCTION

Biologic disease-modifying anti-rheumatic drugs (bDMARDs) and, more recently, targeted synthetic DMARDs (tsDMARDs), have radically changed the long-term outcomes of several rheumatic diseases, including rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA), improving quality of life and making remission an attainable goal [1], [2], [3]. Cancer risk may be increased in patients with RA and other chronic inflammatory diseases not only as a consequence of disease

Study design

This is an observational, nationwide cohort study involving patients with chronic inflammatory rheumatic diseases included in BIOBADASER, the Spanish register on adverse events of advanced therapies in rheumatic diseases (BIOBADASER 3.0, https://biobadaser.ser.es/). BIOBADASER 3.0 is a large national prospective observational cohort of patients with rheumatic diseases starting treatment with any bDMARD or tsDMARD. Patients enrolled in the registry are followed and evaluated at the time an

Patient characteristics

A total of 9,129 patients treated with b/tsDMARDs are included in BIOBADASER 3.0 up to December 2021 (38.9% had rheumatoid arthritis, 24.1% axial spondylarthritis, 20.3% psoriatic arthritis, 3.7% connective tissue diseases and 1.3% vasculitis, among others). Of these, 352 had a prior history of malignancy at the time of enrollment and were selected for this analysis. Overall, 247 (70.2 %) were female and the mean (SD) age was 65.3 (13.0) years. Baseline characteristics and type of prior

DISCUSSION

In this prospective observational study, we did not observe an increase in the overall occurrence of cancer in patients with rheumatic diseases or previous cancers in conjunction with different bDMARD and tsDMARD treatments compared with those patients receiving TNFi. However, due to the study sample size, large IRR confidence intervals for each therapy were obtained. Therefore, these results should be interpreted with caution, and additionally should be verified in larger samples.

Data from

Conclusion

In summary, we have not found an increased risk of incident cancer in patients with rheumatic diseases and/or a previous malignancy with any of the b/tsDMARDs included versus TNFi. Although reassuring, these data should be further confirmed in long-term registries. Moreover, adherence to national screening guidelines for malignancies is recommended.

Contributors

All authors made substantial contributions to the conception and design of this study. The study design was performed by JMC and IC. Subject recruitment and collection of the epidemiological and clinical data were performed by BIOBADASER investigators. FA performed the statistical analysis. JMC, CB, CDT, CPG, JMBM, PV, JMAG and IC drafted the manuscript. All co-authors revised the final manuscript.

Funding

BIOBADASER is partly funded by Spanish Drug Agency (AEMPS), AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Galápagos, Janssen, MSD, Novartis, Pfizer, Sanofi, Samsung Bioepis, and UCB. These pharmaceutical companies equally contributed through a partnership agreement with the Spanish Society of Rheumatology and have played no role in the analysis, interpretation or presentation of these data.

Patient consent for publication

Consent was obtained directly from patients.

Patient and public involvement

Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

Ethics approval

The protocol of the BIOBADASER 3.0 registry was approved by the Ethics Review Committee of Hospital Clinic de Barcelona (FER-ADA-2015-01), which acted as the central committee and all patients signed an informed consent document before participating in the study.

CRediT authorship contribution statement

Juan Molina-Collada: Conceptualization, Data curation, Writing – original draft. Fernando Alonso: Formal analysis. Lucía Otero: Data curation, Formal analysis, Project administration. Cristina Bohórquez: Data curation, Writing – review & editing. César Díaz Torné: Data curation, Writing – review & editing. Carolina Pérez García: Data curation, Writing – review & editing. Juan M. Blanco Madrigal: Data curation, Writing – review & editing. Paloma Vela: Data curation, Writing – review & editing.

Declaration of Competing Interest

Data from randomized controlled trials regarding the risk of malignancy in patients with a history of cancer (except for non-melanoma skin cancer) are very limited, as this is typically an exclusion criterion for study enrollment. Moreover, the long latency of certain malignancies means randomized control trials usually lack sufficient follow-up for detecting such events. In these scenarios, registry data from patients treated in real world clinical practice (as the BIOBADASER 3.0 registry) is

Acknowledgements

The authors thank all of the patients who participated in this study. The authors thank the Spanish Foundation of Rheumatology for providing medical writing/editorial assistance during the preparation of the manuscript (FERBT2022).

References (27)X Mariette et al.Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis

Ann Rheum Dis

(2011)

S Ramiro et al.Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis

Ann Rheum Dis

(2014)

F Montastruc et al.Abatacept initiation in rheumatoid arthritis and the risk of cancer: a population-based comparative cohort study

Rheumatology (Oxford)

(2019)

View full text

© 2023 Elsevier Inc. All rights reserved.