Article Text

Download PDFPDF

Response to: ‘Neuroinflammatory events after anti-TNFα therapy’ by Kaltsonoudis et al
  1. Tine Iskov Kopp1,
  2. Bénédicte Delcoigne2,
  3. Elizabeth V Arkema2,
  4. Melinda Magyari1,3,
  5. Henning Locht4,
  6. Finn Thorup Sellebjerg3,
  7. Rene Lindholm Cordtz5,
  8. Dorte V Jensen5,
  9. Johan Askling2,6,
  10. Lene Dreyer7,8
  1. 1 The Danish Multiple Sclerosis Registry, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
  2. 2 Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  3. 3 Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
  4. 4 Department of Rheumatology, Frederiksberg Hospital, Frederiksberg, Denmark
  5. 5 Center for Rheumatology and Spine Diseases - Gentofte, Rigshospitalet, Hellerup, Denmark
  6. 6 Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
  7. 7 Department of Rheumatology, Aalborg University Hospital, Aalborg, Denmark
  8. 8 Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
  1. Correspondence to Dr Tine Iskov Kopp, Department of Neurology, The Danish Multiple Sclerosis Registry, Rigshospitalet, Kobenhavn 2600, Denmark; tine.iskov.kopp{at}

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

First of all, we would like to thank Dr Kaltsonoudis et al for their interest in our study. Dr Kaltsonoudis et al 1 have raised an interesting suggestion in their correspondence based on their study from 2014.2 They suggest that all patients who are candidates for tumour necrosis factor alpha inhibitor (TNFi) therapy should have a thorough neurological assessment (including brain MRI and neurophysiological tests) before commencing TNFi treatment. Moreover, they believe that the risk of neuroinflammatory events following treatment with TNFis is not disease-dependent, but agent-dependent, and that part of the observed risks following treatment may in fact be present already at treatment start.

In our large observational study,3 we excluded all patients recorded with a hospital contact with a neuroinflammatory diagnosis prior to study entry eliminating patients with existing neuroinflammatory disease that had reached clinical attention. However, as Dr Kaltsonoudis et al argue, we do not know whether some of the patients had a clinically asymptomatic neuroinflammatory disease at time of entry (that is, prior to TNFi treatment start) which may have been aggravated by TNFi use.

In clinical practice, patients with rheumatological disease starting on TNFi treatment are not currently examined for a possible asymptomatic inflammatory neurological disease. In order to do so, we think that additional studies are warranted to evaluate the costs and benefits of such an intervention.

With regards to the risk of neuroinflammatory events being disease- or drug-dependent, we believe that the results from our large study, similar in the two countries under study, are robust and point to the notion that the risk is disease-dependent, although we did not specifically investigate whether there is any interaction between the treated disease and the type of TNFi used to treat it. The hypothesis of disease-specific risks is further supported by studies finding opposite risks for multiple sclerosis among patients with psoriatic arthritis4 and rheumatoid arthritis.5

Ethics statements

Patient consent for publication



  • Handling editor Josef S Smolen

  • Contributors TIK wrote the first draft of the manuscript. All authors critically reviewed the manuscript for intellectual content and approved the final version of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests TIK has received personal fees from Novartis. MM has received grants from Novartis and Biogen, and has received personal fees from Novartis, Biogen, Merck, Sanofi Genzyme and Teva. FTS has received grants and personal fees from Biogen, Merck, Novartis, Sanofi Genzyme and Roche. JA has received grants from AbbVie, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi and UCB. LD has received grants from BMS and has received personal fees from Eli Lilly and Galderma.

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

  • Provenance and peer review Commissioned; internally peer reviewed.

Linked Articles

  • Correspondence
    Evripidis Kaltsonoudis Eleftherios Pelechas Paraskevi V Voulgari Alexandros A Drosos