Discussion
Rheumatoid arthritis is an inflammatory autoimmune disease causing progressive articular destruction and malformation, damage to knee joints is particularly detrimental to patient mobility and quality of life, posing significant economic burden to patients, family and society [1,7,11]. Immunosuppressant medications including GC, conventional and biologic DMARDs, in monotherapy or co-therapy, are mainstays in RA management by reducing inflammatory pathophysiology and providing patients with greater joint mobility, symptomatic relief, and slowing disease progression [1,7-9,12,13]. However, TKA remains the definitive treatment in end-stage disease with severe malformation. Appropriate and timely surgical intervention can restore joint function [14,15], allow patients to reduce dosage of costly medications [8] and facilitate physical activities [16]. Although GC and DMARD management is routinely used to control chronic RA disease activity, long effects of their use perioperatively presently remains unclear. This study will provide a better understanding of the long-term clinical effects of perioperative anti-rheumatic medication use in TKA surgery, aiming to be a reference for future clinical rheumatology and orthopedic management of RA patients.
Unlike osteoarthritis, inflammatory control and suppression of RA disease activity is critical to TKA perioperative management, allowing patients symptomatic relief from pain and stiffness, avoiding ongoing mobility impairment, and facilitating postoperative rehabilitation [7,12,17,18]. HSS knee score, VAS pain and ROM were used as metrics to evaluate joint function and patient satisfaction with surgery. Our study showed that perioperative treatment with DMARDs and GC co-therapy resulted in significant long-term improvements in all of these measures compared to patients managed with only DMARDs. Long-term ROM was additionally also significantly better in co-therapy patients than patients not given anti-rheumatics. This agrees with previous literature describing greater patient satisfaction and better prognosis post TKA in patients treated with GC and DMARD co-therapy [13,19]. Furthermore, GC is reported to provide analgesic effects and improve joint function, supporting why we found greater postoperative ROM in the co-therapy group compared to DMARD alone or no medication regimen [1,9,13,19]. Interestingly, no significant difference in HSS score, VAS pain or ROM was observed between patients given DMARD alone and the no medication control group. One possible explanation for this is that without rapid onset of GC analgesic effects, pain from other joints damaged by systemic RA may interfere with assessment of knee joints after TKA surgery which can decrease patient satisfaction with surgery [20, 21]. Moreover it should be noted that co-therapy patient ROM was statistically similar to the no drug control when measured shortly after surgery prior to patient discharge, but then significantly surpassed both DMARD and control groups by the long-term follow up. This might suggest a gradual improvement in joint mobility following TKA related to long-term steroid use. Overall, this study supports the use of perioperative DMARD and GC co-therapy to improve knee function, patient satisfaction, and decrease pain.
TKA is amongst the most common reasons for allogenic blood transfusion [22]. Avoidance of blood transfusion is ideal to avoid complications including hemolytic reaction, coagulopathy, and allergic reaction. Our study analysis did not indicate any increase in need for blood transfusion related to perioperative DMARD with GC use. Furthermore, anti-rheumatic medication use did not affect hemolytic markers such as WBC, and although DMARD patients had lower postoperative HGB than control, there were no significant differences between these groups when assessing net HGB change post-surgery. There was also one case of allergic shock related to blood transfusion observed in the control group, but it is difficult to draw conclusions from an isolated case and it was not statistically significant. In all, this study suggests no hematologic risk related to perioperative immunosuppressant use in RA patient TKA.
DVT is another complication frequently associated with TKA, however not all clots require intervention with some resolving spontaneously. This study reported no cases of DVT in the GC and DMARD co-therapy group, while one case was reported in the control and four in the DMARD therapy group. This means the co-therapy group actually had the lowest incidence of postoperative DVT, suggesting no increase in DVT risk associated with co-therapy use, which agrees with previous literature [23].
Although our study shows GC and DMARDs to improve joint function, mobility and patient satisfaction with limited complications, conventional practice often suggests discontinuation of immunosuppressants perioperatively for fear of infection, which RA patients are at particular risk for [4]. Prosthetic joint infection (PJI) occurs in about 0.5-2% of TKAs and is a disastrous surgical complication that compromises stability of prosthesis resulting in periprosthetic joint failure [7,24,25]. Literature meta-analysis describes increased risk for PJI up to three years postoperatively in patients using continuous GC therapy [24]. There is also correlation between intra-articular injection of GC and PJI after knee arthroplasty [26]. However, in this case like many, it’s the dose that makes the poison and 2017 guidelines from the American College of Rheumatology directly balance fear infection against risk for inflammatory flare [7]. As perioperative inflammatory damage itself can potentially cause periarticular bone degradation and implant loosening [2,27,28]. Studies have also suggested that a standard dose of GC perioperatively can help with inflammation without drastically increasing infectious risk during the surgical period [29]. Only one case of PJI requiring surgical revision at three years following TKA was reported in our entire study, and although it occurred in the GC and DMARD co-therapy group, it is very difficult to draw any definitive conclusions based on this isolated incident. Especially since pharmacotherapy did not appear to affect perioperative hemolytic measures of inflammation and disease activity including WBC, HGB, CRP, and RF in our study.
Limitations are inevitable in all studies including this one. First, the study cohort was relatively small, as all patient profiles were acquired from the database of a single medical center. Although we were able to draw confident conclusion from our study and patients were selected over an 11-year period covering the breadth of conventional RA presentations, a larger population might have provided greater statistical power and may have allowed for more thorough analytical analysis of surgical complications. Second, many different types of conventional and biologic DMARDs were analyzed combinedly which potentially may mask specific medication affects. However, more detailed categorizing and analysis of patient drug regimens would have required a much larger study population and combined analysis of DMARDs allow our study results to better reflect and apply to a heterogeneous general RA population. Finally, our long-term analysis period with an average 11.4-year follow-up period inevitably contributed to cohort attrition due to death or an inability or refusal to follow-up, which further limited our study size and required that we obtain medical information from close relatives which is rarely as accurate as patient self-reported history.
In conclusion, this study suggests that perioperative co-pharmacotherapy with GC and conventional or biologic DMARDs can result in improved long-term TKA clinical outcomes and patient satisfaction measured through HSS knee score, joint ROM, and VAS pain when compared to management with DMARDs alone or no anti-rheumatic drug treatment, without significant increase of the surgical related complications. Further investigation is warranted with a larger cohort size to better understand more specific medication affects.