Delayed initiation of anti-TNF therapy in the treatment of severe RA increases the risk of total knee replacement (TKR) surgery. Further addition of methotrexate can decrease the risk of future TKR.

Rheumatoid arthritis (RA) is a common autoimmune disorder and imposes a major public health concern. It significantly affects life expectancy, cause of disability that leads to deformities and stiffness of the joints, especially in the hands and feet thereby impairing the quality of life of patients. Patients with severe RA undergoes bone destruction and disability in the knee joints and thus some patients may require a total knee replacement (TKR) surgery. However, the development of effective medical treatments in recent years had decreased the need of TKR surgery. The increased use of synthetic and biological disease-modifying anti-rheumatic drugs (DMARDs) had improved the long-term prognosis of patients with RA. Current anti-rheumatic therapies alleviate pain by either delaying or by preventing joint deterioration. Traditional DMARDs such as methotrexate and anti-TNF-α agents can control disease activity and prevent or delay the joint destruction in patients with RA. However, there is little information available regarding the effect of biological agents on the need for joint replacement surgery.

Rationale behind the research:

There is a little information available regarding the effect of biological agents on the need for joint replacement surgery. Therefore, this study was conducted to examine the effects of anti- TNF therapy on the need of TKR surgery.

Objective:

To evaluate the subsequent risk of TKR surgery due to delayed initiation of anti-TNF therapy in patients diagnosed with severe RA.

Study outcome measures:

• The baseline characteristics were age, sex, body mass index (BMI), underlying diseases, use of concomitant DMARDs (i.e., hydroxychloroquine, methotrexate, leflunomide, cyclosporine, sulfasalazine, azathioprine), erythrocyte sedimentation rate, and C reactive protein level
• The associations between various factors and TKR were calculated using logistic regression analysis
• The odds ratios (ORs) for TKR in the patients with RA prescribed with anti-TNF therapy (years) were calculated, with adjustments for possible confounding factors such as DAS28 and the use of methotrexate

Time Points: Baseline and 3 months

Study Outcomes

Baseline: There were no significant differences observed between groups in baseline characteristics.

• Of the 200 enrolled patients, 84 underwent an early intervention (≤3 years from the diagnosis of RA to the initiation of anti-TNF therapy), and 116 underwent a late intervention (>3 years from the diagnosis of RA to the initiation of anti-TNF therapy) 
• Five (6.0%) patients in the early intervention group underwent TKR compared to 31 (26. 7%) in the late intervention group (p=0.023)
• There was a significantly higher risk of TKR (p=0.004; odds ratio (OR), 5.572; 95% confidence interval (CI), 1.933–16.062) in those receiving biological therapy and a lower risk of TKR (p=0.004; OR, 0.287; 95% CI, 0.122–0.672) in those receiving methotrexate in late intervention group after adjustment of confounding factors (Fig 1)

Figure 1. Higher risk of TKR surgery in those receiving biological therapy and a lower risk in those receiving methotrexate. 

The results of this study indicated that the use of methotrexate decreased the need for TKR in patients with RA which was consistent with the findings of a previous study conducted by da Silva et al. After adjustment of confounding factors, there was an increase in the need of subsequent TKR due to longer duration from the diagnosis of RA to the initiation of anti-TNF therapy. These outcomes may be attributed to the fact that anti-TNF agents could reduce disease activity in patients with RA and either slow or completely halt the progression of joint erosion, even when there are persistent clinical signs of joint inflammation. There could be prolonged effects on the joints.