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Fast relapse upon discontinuation of tumour necrosis factor blocking therapy in patients with peripheral spondyloarthritis
  1. Jacqueline E Paramarta,
  2. Tanja F Heijda,
  3. Dominique L Baeten
  1. Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
  1. Correspondence to Professor Dominique L Baeten, Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands; d.l.baeten{at}

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Tumour necrosis factor (TNF) blockade is effective in axial spondyloarthritis (SpA), including both ankylosing spondylitis and non-radiographic axial SpA,1 as well as peripheral SpA, which comprises psoriatic arthritis (PsA) but also other SpA subtypes.2 It is well established that anti-TNF therapy discontinuation leads to fast relapse in almost all axial SpA patients.3–8 This study aimed to investigate if similar relapses are seen after anti-TNF therapy discontinuation in peripheral SpA.

Twenty-six patients from our randomised clinical trial with adalimumab in peripheral arthritis in non-AS, non-PsA SpA2 were included. Patients had received either 12 (n=12) or 24 weeks (n=14) of adalimumab2 before discontinuation of the anti-TNF therapy. After discontinuation, patients were followed for 16 weeks and seen for a relapse visit upon worsening of symptoms. Relapse was defined as increase of ≥1 swollen joint, or ≥2 points in patient's or physician's global assessment of disease activity or Bath Ankylosing Spondylitis Disease Activity Index. At the relapse visit, or in absence of relapse at the 16 weeks follow-up visit, disease activity parameters were measured. The study was approved by the local ethics committee.

At the time point of adalimumab discontinuation, the disease activity was low (table 1). In all, 11 patients (42.3%) had reached a 66 swollen joint count (SJC66) of zero and 14 patients (53.8%) Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease. After adalimumab discontinuation, 19 patients (73.1%) relapsed after a mean of 10.0±3.2 weeks. Only four patients (16.0%) maintained a SJC66 of zero or ASDAS inactive disease over 16 weeks. At the group level, there was a significant increase in all disease activity parameters after adalimumab interruption (table 1).

Table 1

Disease activity upon start of the randomised clinical trial with adalimumab, the time point of adalimumab discontinuation and at the follow-up visit (upon relapse or, in absence of relapse, at 16 weeks after discontinuation)

The number of patients with relapse increased over time (figure 1A). Relapse was largely based on an increase in SJC66 (12/19 patients), reflecting the peripheral SpA phenotype of this population, but was also associated with worsening of systemic and axial parameters as most SpA patients depict a combination of different disease manifestations.2 Univariate analysis did not identify parameters (including treatment duration, disease activity parameters and demographic or clinical characteristics) to be significantly associated with the occurrence of relapse. In particular, longer duration of adalimumab treatment, SJC66 of zero or ASDAS inactive disease at the time point of adalimumab discontinuation did not result in lower relapse rates (figure 1B–D). However, time to relapse correlated with the duration of adalimumab treatment (R=0.722, p<0.001 assessed by Pearson correlation test) and SJC66 at the time point of adalimumab interruption (R=−0.585, p=0.002).

Figure 1

Cumulative percentage of peripheral spondyloarthritis patients who experienced relapse upon follow-up after discontinuation of treatment with adalimumab. The panel represents the total group of patients (A), and the subanalyses for patients who received 12 versus 24 weeks of adalimumab treatment before antitumour necrosis factor treatment discontinuation (B), had arthritis versus no arthritis at the time point of adalimumab discontinuation (C) and had Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease versus no ASDAS inactive disease at time point of adalimumab discontinuation (D). ASDAS active, ASDAS≥1.3; ASDAS inactive, ASDAS<1.3; SJC, swollen joint count.

In conclusion, our data show a rapid relapse in more than 70% of the peripheral SpA patients within 16 weeks after interruption of TNF blockade. Even patients with complete remission of arthritis or reaching ASDAS inactive disease did rapidly flare. This is in agreement with findings in axial SpA3–8 and preliminary findings in combined axial and peripheral undifferentiated SpA.9 We therefore hypothesise that rapid relapse upon anti-TNF therapy discontinuation is a general SpA feature. It needs to be further investigated whether the patients not flaring within 16 weeks can maintain a longer drug-free remission.


We thank Abbott for the supply of the study medication for this investigator initiated and independent study. Also we would like to thank A van Tillo for her help in this study. DLB is supported by a Vidi grant from The Netherlands Organisation for Scientific Research (NWO).


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  • Contributors All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Study conception and design: JEP and DLB. Data acquisition: JEP and TFH. Analysis and interpretation of the data: JEP and DLB.

  • Funding None.

  • Competing interests None.

  • Patient consent All patients gave written informed consent.

  • Data sharing statement Data of our research article are available upon request. Additional data of this cohort are expected to be published in the future.

  • Ethics approval Approved by the Medical Ethics Committee of the Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.

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

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