Short interruptions of TNF-inhibitor treatment can be associated with treatment failure in patients with immune-mediated diseases

Abstract

Introduction

The prevalence of immune-mediated diseases has increased in the past decades and despite the use of biological treatments all patients do not achieve remission. The aim of this study was to characterise the reasons for short interruptions during treatment with two commonly used TNF-inhibitors infliximab and adalimumab and to analyse the possible effects of the interruptions on immunisation and switching the treatment.

Material and methods

This case-control study was based on retrospective analyses of patient records and a questionnaire survey to clinicians. A total of 370 patients (194 immunised cases and 172 non-immunised controls, 4 excluded) were enrolled from eight hospitals around Finland. Eleven different diagnoses were represented, and the largest patient groups were those with inflammatory bowel or rheumatic diseases.

Results

Treatment interruptions were associated with immunisation in patients using infliximab (p < .001) or adalimumab (p < .000001). Patients with treatment interruptions were more likely to have been treated with more than one biological agent compared to those without treatment interruptions. This was particularly prominent among patients with a rheumatic disease (p < .00001). The most frequent reason for a treatment interruption among the cases was an infection, whereas among the control patients it was remission. The median length of one interruption was one month (interquartile range 1–3 months).

Conclusion

Our results suggest that the interruptions of the treatment with TNF-inhibitors expose patients to immunisation and increase the need for drug switching. These findings stress the importance of careful judgement of the need for a short interruption in the biological treatment in clinical work, especially during non-severe infections.

Keywords:

• Infliximab
• adalimumab
• Crohn disease
• ulcerative colitis
• rheumatoid arthritis
• juvenile idiopathic arthritis
• immunisation
• treatment interruption

Acknowledgements

We appreciate the participation of the BLING Project Group members [Perttu Arkkila, Nina Barner-Rasmussen, Clas-Göran af Björkesten, Anja Eberl, Fredrik Forsström, Martti Färkkilä, Johanna Haapamäki, Kalle Jokelainen, Miikka Keski-Keturi, Kaisa Kosunen, Pauliina Molander, Daniela Norio, Hannu Nuutinen, Minna Takkunen (Gastroenterology, University of Helsinki and Helsinki University Hospital, Finland); Päivi Lindahl (Department of Pediatrics, University of Helsinki and Helsinki University Hospital, Finland); Tiina Levälampi (Ophthalmology, University of Helsinki and Helsinki University Hospital, Finland); Airi Jussila (Gastroenterology, Tampere University Hospital, Finland); Anna Kinnunen, Matleena Lopperi, Marja Pertovaara, Vappu Rantalaiho, Jarno Rutanen, Susanna Sihvonen, Terhi Uotila, Vladena Vinograi, Maritsa Vesalainen (Centre for Rheumatology, Tampere University Hospital, Finland); Merja Malin, Kati Markula-Patjas (Department of Pediatrics, Tampere University Hospital, Finland); Juha Asikainen, Jelena Borodina, Pekka Hannonen, Kirsi Paalanen, Anna Sillanpää, Kati Soininen, Juha Taavela, Tuomas Rannio (Rheumatology, Jyväskylä Central Hospital, Finland); Sami Turunen (Gastroenterology, Oulu University Hospital, Finland); Markku Heikkinen (Gastroenterology, Kuopio University Hospital, Finland); Markku Kauppi, Heini Pohjankoski (Rheumatology, Päijät-Häme Central Hospital, Finland); Johanna Kärki, (Kanta-Häme Central Hospital, Finland)]

We also thank the assisting personnel involved in the study, most notably Pamela Edgren, Pauli Pirinen (United Medix Laboratories, Helsinki, Finland), Virpi Pelkonen, Pirkko Tuukkala (Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland) and Seija Salonen (Rheumatology, Jyväskylä Central Hospital, Jyväskylä, Finland).

Disclosure statement

The following authors declare that there is no conflict of interest: Aalto K, Haapala A-M, Keskitalo P, Kokko A, Kolho K-L, Korkatti K, Koskela R, Kröger L, Lamberg T, Mikola K, Mäkinen H, Mälkönen T, Sard S, Valtanen S, Vidqvist K-L.

Eklund, K. has received lecture and consultation fees from SOBI, Pfizer, Novartis, Lilly and Janssen.

Huilaja, L. has received educational grants from Takeda, Janssen-Cilag, Novartis, AbbVie and LEO Pharma, honoraria from Sanofi Genzyme, Novartis, Abbvie and UCB Pharma for consulting and/or speaking and is an investigator for Abbvie.

Isomäki P. has received a grant from Pfizer, personal fees from Abbvie, Pfizer, Lilly and Roche and non-financial support from Abbvie and Roche.

Jokiranta, TS. has received lecture and consultation fees from the following pharmaceutical companies producing biologicals used for the patient groups mentioned in this study: Abbvie, MSD, Novartis, Pfizer, Roche, Sandoz, Takeda.

Kyllönen, M. has been on conference and congress trips sponsored by followed companies Novartis, Roche, Bristol-Myers-Squipp, Sanofi, Pfizer and UCB and has received lecture fee from Abbvie.

Lahtinen, P. has received lecture fees from Takeda.

Leinonen, S. has consultation and lecture fees from AbbVie − 2019 and lecture fees from Santen, UCBPharma, Théa Nordic.

Sipponen, T. has received consultation or lecturer fees from BMS, Janssen-Cilag.

Pfizer, Roche, and Takeda and study grants from Janssen-Cilag and Takeda.

Sokka-Isler, T. has received personal fees from Abbvie, BMS, Celgene, Medac, Merck, Novartis, Orion Pharma, Pfizer, Roche, Sandoz, UCB and Bohringer Ingelheim and non-financial support from DiaGraphIT.

Vähäsalo, P. has received lecture and consultation fees from Abbvie, SOBI, Pfizer, Novartis, Roche and MSD.

Additional information

Funding

This study was funded by the University of Helsinki, HUS EVO-fund and TEKES (SalWe Get It Done – Personalised Diagnostics and Care Research Program).