The association of depression and anxiety with treatment outcomes in patients with rheumatoid arthritis - a pooled analysis of five randomised controlled trials

Background: Rheumatoid arthritis (RA) is an inflammatory autoimmune condition associated with an increased risk of developing depression and anxiety. Depression and anxiety are associated with worse outcomes in RA, but the magnitude of the effect of each condition on RA outcomes is unclear. It is also unknown how pharmacological treatment of depression affects RA outcomes. Objective: The primary aim of this study was to investigate the association of comorbid depression and anxiety with remission in patients with RA. Secondary aims were to determine the association between comorbid depression and anxiety on patient-reported outcomes and the relationship between concomitant use of antidepressants and remission in patients with depression. Design: Data from patients with moderate to severe RA were pooled from five randomised controlled trials investigating tocilizumab and conventional synthetic disease-modifying agents. Methods: Remission was defined as a clinical disease activity index (CDAI) of <= 2.8 and simple disease activity index (SDAI) of <= 3.3. The association between the time to reach remission and depression and anxiety was analysed using Cox proportional hazard analysis. Results: Individual patient data were available from 5502 subjects, of whom 511 had depression, 236 had anxiety and 387 were using antidepressants. Depression was significantly associated with reduced remission [adjusted HR (95% CI): 0.62 (0.48-0.80), p < 0.001 and adjusted HR (95% CI): 0.59 (0.44-0.79), p < 0.001] using CDAI and SDAI, respectively. Depression was associated with a lower likelihood of achieving more subjective outcomes (<= 1 physician global assessment, <= 1 patient global assessment) and <= 1 28-swollen joint count, but not <= 1 28-tender joint count or C-reactive protein measurement. Treatment with antidepressants did not improve outcomes for patients with depression. Anxiety was not significantly associated with RA remission. Conclusion: Comorbid depression, but not anxiety, was associated with less frequent remission. Concomitant antidepressant use was not associated with improvements in RA outcomes in patients with depression.