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.