Withdrawal of Infliximab Therapy in Ankylosing Spondylitis in Persistent Clinical Remission, Results From the REMINEA Study

Results From the REMINEA Study

Mireia Moreno; Jordi Gratacós; Vicenç Torrente-Segarra; Raimon Sanmarti; Rosa Morlà; Caridad Pontes; Maria Llop; Xavier Juanola; REMINEA study Group

Disclosures

Arthritis Res Ther. 2019;21(88) 

In This Article

Discussion

This is the first prospective study to show that the majority of longstanding AS patients in persistent clinical remission presented clinical relapse after infliximab withdrawal within the following 12 months. Moreover, although the reintroduction of infliximab was safe and effective in most cases, around half of the patients did not achieve remission after treatment reintroduction and in an additional 10% the treatment was ineffective, obliging us to change the prescription.

Data from clinical practice and registries have suggested that in patients with sustained clinical remission (i.e., more than 6 months), reducing the treatment dose may be a desirable therapeutic goal .[5–7] For example, the recent EULAR guidelines [13] incorporate the tapering of biological therapy for these patients as a new recommendation, even though the data supporting this policy are limited due to the absence of randomized controlled studies. Recently our group have been communicated a randomized pragmatical study demonstrating the no inferiority of a regime of dose reduction compared with full doses in these patients .[14]

Many previous studies have suggested that treatment withdrawal in AS patients leads to a reactivation of the disease .[8,15–17] Nonetheless, in most studies, withdrawal is performed in patients who are not in clinical remission, and some of them even present high CRP serum levels .[15,16] Recently, a controlled and randomized study in non-radiographic axSpA patients reported in patients who achieved sustained remission with adalimumab more reactivation of the disease in the treatment withdrawal compared with the control arm (patients without suspension of anti-TNF) .[10] However, some official recommendations, based only on clinical practice and in the expert opinion, suggest the possibility of withdrawing treatment in AS patients with persistent clinical remission after a notable reduction in anti-TNF therapy .[8,18]

The data we reported in AS patients were in agreement with the results previously reported by Landewé et al. in non-radiographic axSpA .[10] Unfortunately, in our study as did Landewé et al., the withdrawn of treatment was performed without dose reduction. However, all the patients previous dose reduction were in persistent remission without any analgesic or anti-inflammatory treatment that could mask the clinical symptoms.

Few studies are focused on the clinical response to re-treatment after withdrawal of anti-TNF therapy in patients with axSpA, suggesting as overall that the reintroduction of treatment is comparable to the previously observed .[15,19,20] In contrast, our data indicate that the reintroduction of biological therapy (without previous premedication), although it was safe, only half of the patients achieved clinical remission, as they had before the discontinuation of anti-TNF. These data are in agreement with data recently reported by Landewé et al. in non-radiographic axSpA using adalimumab .[10] Furthermore, in our study, in 10% of the patients, the re-treatment was ineffective, obliging us to change the anti-TNF therapy.

The patients we included in the study presented definite AS and had received only infliximab treatment as first-line anti-TNF therapy. The baseline characteristics of our patients are quite similar to those in previous studies of anti-TNF therapy (22, 23). The baseline clinical characteristics we found to be associated with clinical remission after infliximab treatment—younger age, short disease duration, and high CRP levels—were in agreement with the previously published data .[21] Unfortunately, a complete study of clinical and biological factors associated with the presence of relapse during the following 12 months did not yield any positive results. The sample size of our study seems to be the main factor associated with the negative results observed; however, other larger studies also failed to obtain any results in this regard .[10,20]

Overall, the results we reported here suggest that the decision to withdraw treatment should be taken with considerable caution, and it seems unreasonable to propose withdrawal as an objective of the treatment strategy, at least at present, in the absence of any objective predictive factors of persistent clinical remission after treatment withdrawal.

The study has certain limitations that must be mentioned. The sample size is too small to assess factors related to the persistence of remission or the presence of a flare after treatment withdrawal; however, other larger study also failed in this subject .[10] Similarly, since all the patients were in treatment with infliximab, the results need to be corroborated in other anti-TNF agents, but the results published by Landewé et al. [10] using adalimumab are quite similar. Furthermore, our schedule of treatment did not incorporate a strategy of infliximab reduction doses before treatment withdrawal, so we cannot definitively rule out the possibility of withdrawal treatment in patients under persistent remission after intensive doses reduction. The clinical remission period before withdrawal of infliximab treatment (6 to 12 months) does not exclude the possibility of some different results in patients with a longer period of time in clinical remission. Finally, the study began before the publication of the definite new ASAS remission and relapse criteria; however, the criteria applied are widely accepted and used in the clinical practice.

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