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Crohn's disease patients treated with adalimumab benefit from co-treatment with immunomodulators
  1. Mirthe E van der Valk1,
  2. Martijn G H van Oijen1,
  3. Marije Ammerlaan2,
  4. Peter D Siersema1,
  5. Bas Oldenburg1
  1. 1Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2ApotheekZorg, Sittard, The Netherlands
  1. Correspondence to Dr Bas Oldenburg, Department of Gastroenterology and Hepatology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands; b.oldenburg{at}

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We read with interest the study by Sokol et al in Gut, emphasising the need for co-treatment with immunomodulators in patients receiving infliximab maintenance therapy. Concomitant use of immunosuppressives was associated with reduced disease activity and infliximab dose escalation, presumably through a lowered frequency of antibody formation.1

Although adalimumab is a 100% human anti-tumour necrosis factor monoclonal antibody, it is not devoid of immunogenicity. Antibodies against adalimumab have been reported in 2.6–38% of patients treated for Crohn's disease or rheumatoid arthritis.2 However, the long-term efficacy of the combination of adalimumab plus immunosuppressives in this setting is not known. One observational study from Karmiris et al performed at a single tertiary care centre evaluated the effect of use of immunosuppressives in Crohn's disease patients treated with adalimumab. Immunosuppressive co-treatment did not affect the treatment outcome and did not inhibit the induction of antibodies against adalimumab.2 Therefore, the current paradigm is to treat Crohn's disease patients with adalimumab monotherapy.3

Thus, little is known about the effect of use of immunosuppressives in Crohn's disease patients treated with adalimumab in actual clinical practice. We addressed this issue using data obtained from the registry of ‘ApotheekZorg’, which is responsible for the exclusive nationwide distribution of adalimumab in the Netherlands.

Data were available for a total of 2685 Crohn's disease patients (63% women, mean age 37 (SD 13) years), who were treated with adalimumab between 2004 and 2010. In total, 967 (36%) of all patients were treated in a university medical centre setting, 859 (32%) received co-treatment with thiopurines and 88 (3%) were treated with methotrexate, while 1149 (54%) were previously treated with infliximab. The induction dose of adalimumab was 160–80 mg in 1557 (58%) patients, 80 mg in 690 (26%) patients and 40 mg in 438 (16%) patients. After a median use of 12 months, 2110 (79%) patients were on a 40 mg adalimumab dose every other week, 18 (1%) patients on 80 mg dose every other week and 557 (21%) patients on 40 mg dose weekly.

During follow-up, 700 (26%) patients discontinued treatment after a median use of 6 months. As shown in table 1, co-treatment with thiopurines (adjusted (adj) OR 0.35, 95% CI 0.28 to 0.43) or methotrexate (adj OR 0.42, 95% CI 0.24 to 0.79), and male gender (adj OR 0.70, 95% CI 0.58 to 0.85) were independently associated with a lower risk of discontinuation, whereas previous infliximab treatment (adj OR 1.32, 95% CI 1.10 to 1.58) and treatment at a referral centre (adj OR 1.22, 95% CI 1.01 to 1.48) were independently associated with a higher risk for discontinuation.

Table 1

Univariate and multivariate analysis of the association between demographic and treatment characteristics and discontinuation of adalimumab

To our knowledge, this is the first report suggesting a beneficial effect of immunosuppressive co-medication in adalimumab users with Crohn's disease. The highly significant reduction of adalimumab discontinuation in these patients might justify standard methotrexate or thiopurine co-treatment in clinical practice. A head-to-head comparison between adalimumab and adalimumab plus immunosuppresive co-treatment in patients with Crohn's disease is warranted.



  • Disclosures Dr B Oldenburg has received an unrestricted grant from MSD and Abbott Immunology. Dr M G H van Oijen has received an unrestricted research grant and has served as a consultant for Abbott Immunology.

  • Competing interests None.

  • Provenance and peer review Not commissioned; not externally peer reviewed.