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High burden of adverse events is associated with reduced remission rates in early rheumatoid arthritis

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Abstract

Adverse events (AEs) are common during disease-modifying antirheumatic drug (DMARD) treatment, but their influence on treatment results is unclear. We studied AEs in relation to disease activity in early rheumatoid arthritis (RA). Ninety-nine patients started intensive treatment with three conventional synthetic DMARDs (csDMARDs) and oral prednisolone, and were randomized to a 6-month induction treatment with infliximab or placebo. All AEs during the first 12 months of treatment were recorded. We scored each AE based on severity (scale 1–4) and defined the burden of AEs as the sum of these scores. Patients were divided into tertiles according to the burden of AEs. As outcomes, we assessed 28-joint disease activity score (DAS28) levels and remission rates at 12 and 24 months. Three hundred thirty-one AEs in 99 patients were reported, and 27 (8%) were categorized as severe or serious. Mean burden of AEs per patient was 5.4 ± 4.3. Seventy-nine AEs (24%) led to temporary (n = 52) or permanent (n = 27) csDMARD discontinuation. Of discontinuations, 1, 21, and 57 were detected in the first, second, and third tertiles, respectively. DAS28 remission rates decreased across tertiles at 12 months (94, 94, and 76%; p for linearity 0.029) and at 24 months (90, 86, and 70%; p for linearity 0.021). Mean DAS28 levels increased across tertiles at 12 months (1.5 ± 1.0, 1.7 ± 0.9, and 1.9 ± 1.2; p for linearity 0.021) and at 24 months (1.4 ± 0.8, 1.6 ± 1.0, and 1.9 ± 1.1; p for linearity 0.007). High burden of AEs is associated with higher disease activity and lower likelihood of remission in early RA.

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Acknowledgements

The authors would like to thank all participating patients, other members of the NEO-RACo study group (Eeva Alasaarela, Harri Blåfield, Kari K. Eklund, Mikko Hakola, Pekka Hannonen, Kirsti Ilva, Heikki Julkunen, Oili Kaipiainen-Seppänen, Markku Kauppi, Aulikki Kononoff, Maija-Liisa Krogerus, Kari Laiho, Riitta Luosujärvi, Reijo Luukkainen, Timo Möttönen, Helena Niinisalo, Ritva Peltomaa, Jari Pöllänen, Tea Uusitalo, Toini Uutela, Heikki Valleala, Kaisa Vuori, Leena Laasonen, Eeva Moilanen, Riina Nieminen, and Katriina Vuolteenaho), and the study nurses for their contribution.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, University of Turku and Turku University Hospital, Kiinamyllynkatu 4–6, P.O. Box 52, 20521, Turku, Finland

    Laura Kuusalo

  2. South Karelia Central Hospital, Valto Käkelän katu 1, 53130, Lappeenranta, Finland

    Kari Puolakka

  3. Unit of Primary Health Care, University of Helsinki and Helsinki University Hospital, Tukholmankatu 8 B, 00290, Helsinki, Finland

    Hannu Kautiainen

  4. Department of General Practice, University of Helsinki, Helsinki, Finland

    Hannu Kautiainen

  5. Unit of Primary Health Care, Kuopio University Hospital, Kuopio, Finland

    Hannu Kautiainen

  6. Department of Internal Medicine, University of Oulu and Oulu University Hospital, Kajaanintie 50, 90220, Oulu, Finland

    Anna Karjalainen

  7. Seinäjoki Central Hospital, Hanneksenrinne 7, 60220, Seinäjoki, Finland

    Timo Malmi

  8. ORTON Orthopaedic Hospital, Tenholantie 10, 00280, Helsinki, Finland

    Leena Paimela

  9. Rheumatology, University of Helsinki and Helsinki University Hospital, 00014, Helsinki, Finland

    Marjatta Leirisalo-Repo

  10. Department of Internal Medicine, Centre for Rheumatic Diseases, Tampere University Hospital, Tampere, Finland

    Vappu Rantalaiho

  11. Faculty of Medicine and Life Sciences, University of Tampere, Tampereen Yliopisto, PL 100, 33014, Tampere, Finland

    Vappu Rantalaiho

Authors
  1. Laura Kuusalo
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  2. Kari Puolakka
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  3. Hannu Kautiainen
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  4. Anna Karjalainen
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  5. Timo Malmi
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  6. Leena Paimela
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  7. Marjatta Leirisalo-Repo
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  8. Vappu Rantalaiho
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Consortia

for the NEO-RACo Study Group

  • Eeva Alasaarela
  • , Harri Blåfield
  • , Kari K. Eklund
  • , Mikko Hakola
  • , Pekka Hannonen
  • , Kirsti Ilva
  • , Heikki Julkunen
  • , Oili Kaipiainen-Seppänen
  • , Markku Kauppi
  • , Aulikki Kononoff
  • , Maija-Liisa Krogerus
  • , Kari Laiho
  • , Riitta Luosujärvi
  • , Reijo Luukkainen
  • , Timo Möttönen
  • , Helena Niinisalo
  • , Ritva Peltomaa
  • , Jari Pöllänen
  • , Tea Uusitalo
  • , Toini Uutela
  • , Heikki Valleala
  • , Kaisa Vuori
  • , Leena Laasonen
  • , Eeva Moilanen
  • , Riina Nieminen
  •  & Katriina Vuolteenaho

Corresponding author

Correspondence to Laura Kuusalo.

Ethics declarations

Conflict of interest

Laura Kuusalo has received honoraria and consulting fees (less than $10,000 each) from Bristol-Myers Squibb and Pfizer. Kari Puolakka has received honoraria and consulting fees (less than $10,000 each) from Abbvie, Bristol-Myers Squibb, MSD, Pfizer, Roche, and UCB. Hannu Kautiainen has received honoraria (less than $10,000 each) from AbbVie and Pfizer. Anna Karjalainen has received honoraria (less than $10,000 each) from MSD, Novartis, Roche, and UCB. Timo Malmi has received an honorarium (less than $10000) from Pfizer. Leena Paimela has received honoraria and consulting fees (less than $10,000 each) from Abbvie, Bristol-Myers Squibb, Pfizer, and Roche. Marjatta Leirisalo-Repo has received honoraria and consulting fees (less than $10,000 each) from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, Pfizer, Regeneron, and Roche. Vappu Rantalaiho has received an honorarium (less than $10000) from Bristol-Myers Squibb.

Ethical standards

The study protocol was approved by the ethics committee of the Hospital District of Helsinki and Uusimaa. The patients provided written informed consent. The study was conducted according to the Declaration of Helsinki and has been registered at http://www.clinicaltrials.gov (NCT00908089).

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Kuusalo, L., Puolakka, K., Kautiainen, H. et al. High burden of adverse events is associated with reduced remission rates in early rheumatoid arthritis. Clin Rheumatol 37, 1689–1694 (2018). https://doi.org/10.1007/s10067-017-3958-1

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  • DOI: https://doi.org/10.1007/s10067-017-3958-1

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