Background/Purpose

Rheumatoid arthritis (RA) flares are predictive of structural damage even in case of stable disease course. No definition for flare has been validated to date. The objective of our study was to determine the rate of flares in RA patients on stable LDA or remission. We considered flares assessed at each visit (FV), self-reported flares (SRF), and major flares (MF) defined as flares requiring a change in the DMARD or in the biologic dose or lasting more than 30 days. We investigated the relationships between flare rate and baseline characteristics of patients or treatments. We further investigated whether flare rate could be related to survival of remission or LDA.

Methods

We conducted an observational study on RA patients, treated with subcutaneous anti-TNF-alpha, on stable (> 6 months) LDA or remission, with a minimum follow up of one year. We investigated associations of flare rates with age, sex, disease duration, baseline activity indices, positive ACPA and RF, concurrent fibromyalgia, smoking, previous biologic failures, treatment with methotrexate (MTX), prednisone (PDN) dose, and dose of biologics. Survival of remission or LDA according to flare rate was calculated with Kaplan-Meier curves. 

Results

Out of 86 patients, 11 patients were excluded because of pregnancy or little reliability in recalling events, and 55 patients achieved a stable LDA or remission. We observed 237 flares in 55 patients with a mean follow up of 70.72 ± 30.41 months: 91 FV, 146 SRF, and 18 MF. Overall flare rate was 0.80 ± 0.79 flares/year, rate of FV was 0.26 ± 0.28, rate of SRF was 0.54 ± 0.70 and rate of MF was 0.05 ± 0.10. Flare rates on remission or LDA were not significantly different (0.67 ± 0.75 and 1.08 ± 1.29 flares/year, respectively). Mean time to flare was 23.62 ± 21.21 months and was inversely correlated with flare rate on LDA periods (Spearman’s correlation, R² = -0.405, p 0.024).  Overall flare rate and SRF rate were higher in patients with concurrent fibromyalgia and active smokers (Table). No significant differences were seen between full dose and low dose biologic, between different PDN doses or between combination with and without MTX, although fewer flares were observed on MTX (Table). Patients na•ve to biologics had many fewer flares than those who had a failure of one biologic or specifically of one anti-TNF-alpha (Table ). PDN was the most used medication in case of flare (138/237, 58.2% of flares). Mean increase of PDN compared with previous dose was 3.66 ± 5.81 mg daily. Flare rate < 1 flare/year or a SRF rate  < 0.5 flares/year were associated with a longer survival of LDA/remission (p 0.029 and p 0.037 respectively).

Conclusion

Flares are frequent on LDA or remission. Patients that have already failed a biologic treatment, active smokers and with concurrent fibromyalgia patients seem to be more prone to experience flares. SRF account for most of the flares and have the greatest impact on survival of remission.

Table. Flare rate.