Low-dose prednisolone in rheumatoid arthritis: adverse effects of various disease modifying antirheumatic drugs

To assess the incidence and severity of disease modifying antirheumatic drug (DMARD)-induced adverse effects (AE) in patients with rheumatoid arthritis (RA) taking/not taking glucocorticoids (GC). More specifically, we tested whether GC can prolong the survival time of DMARD in patients receiving combination therapy.

In a retrospective study of 154 patients with RA, data were examined for DMARD therapy and duration of low-dose GC ((3/4) 7.5 mg prednisone equivalent/day). Patients were followed for 2-62 months, and AE were graded following WHO criteria.

GC therapy significantly increased the duration of therapy with sulfasalazine (SSZ) from 10.4 +/- 2.3 to 22.5 +/- 1.9 months and for methotrexate (MTX) from 21.8 +/- 2.9 to 43.3 +/- 2.7 months. Stratifying the withdrawal of DMARD for occurrence of AE and loss of efficacy revealed that GC comedication significantly increased the time until AE for users of MTX (3.0 +/- 0.6 vs 18.8 +/- 1.3 mo; p < 0.05), hydroxychloroquine (HCQ; 34.5 +/- 4.6 vs 54.4 +/- 5.1 mo; p < 0.05), and gold (6.6 +/- 0.9 vs 10.5 +/- 0.9 mo; p < 0.05). In patients taking SSZ the time until cessation due to loss of efficacy increased significantly under GC comedication (16.8 +/- 1.2 vs 31.3 +/- 2.9 mo; p < 0.05). However, in patients taking azathioprine (AZA) the duration of therapy decreased from 44.4 +/- 2.6 to 22.3 +/- 1.6 months under GC due to both time until AE and loss of efficacy. Patients under comedication of MTX + GC, HCQ + GC, and AZA + GC experienced significantly more AE compared to the respective DMARD monotherapy. A highly significant reduction was observed in the frequency of erosive RA in patients with GC comedication (n = 30; 49.1%) compared to patients without low-dose GC (n = 81, 80.4%; OR 4.05, 95% CI 1.91-8.66, p < 0.0001).

Low-dose GC retard radiological progression of RA and exhibit a differential effect on survival of DMARD and degree of AE due to DMARD. Further studies are warranted to address safety and interactions of chronic low-dose GC in RA patients treated with DMARD.