Background The treatment of rheumatoid arthritis (RA) has been transformed in by the development of novel agents focusing on biological factors. The idea of “treat to target” has emerged. Early aggressive treatment with methotrexate (MTX) and tumor necrosis factor inhibitors can lead to clinical, radiological, even functional remission in a large proportion of patients with RA. However, there is still a population of patients with refractory RA, even with the recent advances in disease management. A few clinical studies have reported the efficacy of a combination of MTX, a TNF inhibitor, and tacrolimus (TAC). However, few papers have so far compared the escalation of infliximab (IFX) and the addition of TAC.

Objectives The aim of this study was to compare dose escalation of IFX and adding TAC in rheumatoid arthritis patients with an inadequate response to IFX and MTX combination therapy.

Methods Twenty-two RA patients with an inadequate response to IFX and MTX combination therapy were included in this study (11 patients on escalation IFX, 11 patients on adding tacrolimus). The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), matrix metalloproteinase-3 (MMP-3), the swollen and tender joint counts, the Disease Activity Score in 28 joints using ESR (DAS28-ESR) were examined at baseline and six months later. The remission rate and adverse effects at 6 months were also examined.

Results There were no significant differences in the patient characteristics of each group. The IFX dose in the escalation group was 300-500 mg (an average of 345.5 mg). The TAC dose in the adding TAC group was 1-3 mg/day (an average of 1.9 mg/day).

CRP, MMP-3, ΔDAS28-ESR showed no significant difference between the two groups after 6 months. ESR fell more in the TAC group than in the escalation group. Five of eleven patients were in remission 6 months after escalation of IFX, and seven of eleven patients were in remission at 6 months after the onset of TAC.

No serious adverse events were observed during the follow-up periods. Two infections were recorded. One infusion reaction occurred in the escalation group and, non-disseminated herpes zoster occurred in the TAC group.

Conclusions The addition of low dose TAC improved the clinical variables in this case series with RA patients refractory to anti-TNF therapy with MTX. Moreover, the response was remarkable and majority of the patients achieved clinical remission.

Adding TAC was therefore found to have a therapeutic effect in RA patients with an inadequate response to infliximab therapies that was comparable to or better than the escalation of IFX.

1. Taio Naniwa, Maiko Watanabe, Shogo Banno, Tomoyo Maeda. Adding low dose tacrolimus in rheumatoid arthritis patients with an inadequate response to tumor necrosis factor inhibitor therapies. Rheumatol Int (2009) 29:1287–1291

Disclosure of Interest None Declared