Background Prednisone (PRD) has been the basis of giant cell arteritis (GCA) treatment. Although adverse effects of high-dose (> 7,5 mg/day) PRD therapy are well known, there are not comparative studies evaluating the prednisone-sparing effect and outcomes of combined treatment regimes (i.e. PRD in combination with methotrexate [MTX] and/or methylprednisolone IV pulses [MPP]).
Objectives To investigate the role of MTX and MPP in GCA treatment, and the impact of combined treatment with PRD and MTX and/or MPP in reducing PRD cumulative dose.
Methods Retrospective study. 41 GCA patients with positive temporal artery biopsy were included. Univariate analyses, Kaplan-Meyer survival analysis and Cox regression including age, sex, clinical variables and treatment variables were performed using SPSS 19.0 package. Primary end-point was the time to complete remission (defined as remission of all symptoms and normalization of C-reactive protein with a maintenance daily dose of PRD of 7,5 mg or less). Four treatment groups were defined: 1) PRD (20 patients); 2) PRD and MTX (9 patients); 3) MPP and PRD (4 patients); 4) MPP, PRD and MTX (8 patients). Cumulative 6 and 12-month PRD dose was calculated in all patients.
Results 28 (68,3%) women and 13 (31,7) men. Mean age at diagnosis was 75,1 ± 7,3 years. Median duration of symptoms before diagnosis was 1 (1-19) months and follow-up since the diagnosis of GCA was 37,6 (9,4-215,8) months. No epidemiological or clinical significant differences between the treatment groups were found. Median cumulative 6 and 12-month PRD dose were 2,90 (1,27-9,87) and 4,02 (1,74-16,53) grams respectively in the total group. Patients treated with MTX (17) received a significantly minor PRD dose at 6 months (2,50 g vs. 3,44 g, p=0,003) and 12 months (3,63 g vs. 5,08 g, p=0,006), and median cumulative 6 and 12-month PRD dose were significantly minor in treatment group 4 (2,14 g and 3,00 g) than in groups 1 (3,44 g and 5,08 g), 2 (2,61 g and 3,91 g) and 3 (3,43 g and 4,62 g) (p = 0,003 and 0,001). Patients treated with MMP (12) received a median dose of 750 (375-2000) mg of IV methylprednisolone. Median time to complete remission was significantly shorter in patients treated with methylprednisolone: 180 (87-479) vs. 293 (93-886) days (p=0,007). Kaplan-Meier survival analysis showed that combined treatment with MPP, PRD and MTX was more efficient in achieving total remission (p=0,016, log rank test). Treatment with MPP and PRD (OR 6,71 [1,85-24,33], p=0,004) and with MPP, PRD and MTX (OR 3,59 [1,24-10,38], p=0,018) were independently associated with primary end-point (Cox regression).
Conclusions The results of this study suggest that combined therapy with MMP, PRD and MTX is more efficient for GCA treatment than classical treatment based on PRD alone. It seems that MMP and MTX may play different roles when associated with PRD: MMP, dispensed at diagnosis, reduces the time necessary to achieve complete remission (remission-induction effect) and MTX reduces the cumulative dose of PRD (prednisone-sparing effect). Long-term prospective controlled studies are needed to confirm these results.
In conclusion, combined therapy with MMP, PRD and MTX is more efficient in achieving complete remission and allow a significant reduction of cumulative PRD dose in patients with GCA.
Disclosure of Interest: None Declared