Since the arrival of biologics in the late 1990s, the incidence rate of total knee replacement (TKR) in rheumatoid arthritis patients has declined in Denmark, a nationwide registry study indicated.

In 1996, in the era before biologic disease-modifying antirheumatic drugs (bDMARDs), the incidence rates of total hip replacement (THR) and TKR were 3 and 14 times greater, respectively, in Danish RA patients relative to the general population, reported Rene Lindholm Cordtz, MD, of Rigshospitalet-Gentofte, Copenhagen, and colleagues in Annals of the Rheumatic Diseases.

The introduction of bDMARDs was associated with a reduction in TKR but not in THR, which had already begun to decline before the era of tumor necrosis factor (TNF) inhibition.

“If treatment with bDMARD reduces the need for joint replacements, this will likely change the cost-effectiveness of these drugs,” Cordtz and co-authors wrote. “Joint replacements are expensive procedures and carry the risk of potential adverse events; and risk estimates for complications are increased in patients with RA.”

Cordtz’s group identified 30,404 patients with incident RA from 1996 to 2011 in the Danish National Patient Register and matched them for age, sex, and municipality with 297,916 general-population controls. About 70% were women whose average age was in the mid-50s. More in the RA group had comorbidities such as pulmonary or heart disease and diabetes. All were followed for up to 5 years.

Age and sex standardized 5-year incidence rates for THR and TKR per 1,000 person-years were calculated for RA patients and controls in 6-month periods. Levels and trends in the pre-bDMARD (1996-2001) era were compared with those of the bDMARD era (2003–2016) using segmented linear regression interrupted by a 1-year lag period (2002). The time of introduction of bDMARDs was set to the calendar year 2000.

In 1996, the incidence rates for THR and TKR were 8.72 and 5.87, respectively, among RA patients, and 2.89 and 0.42, respectively, in controls. In the pre-bDMARD era, the incidence rate of TKR increased by 0.19 per year (P=0.173), but then decreased at –0.20 per year (P=0.083) in the bDMARD era. Among controls, in contrast, TKR incidence increased throughout the period, rising by 0.21 per year during 1996-2003 and by 0.08 during 2003-2016.

From 1996 to 2016, the incidence rate for THR decreased among patients with RA by –0.36 per year but increased slightly among controls at 0.02 per year.

The authors pointed out that their observed incidence rates and trends for THR and TKR in Denmark were very similar to those reported this year in Welsh and English RA patients. A 2014 study also found a 28% reduction in knee and hip replacement surgeries for U.S. RA patients since the introduction of TNF inhibitors. In 2012 MedPage Today reported that biologics had substantially reduced hospitalizations in Irish RA patients.

“There have been numerous studies documenting that the rates of THR/TKR are reduced after aggressive management of RA, and this is especially true since the introduction of biologics,” Umbreen Hasan, MD, MBA, of Allina Health in Minneapolis, told MedPage Today. “In my own practice we have noted a decline in arthroplasties secondary to inflammatory arthritis when a treat-to-target approach is utilized,” she continued. “It makes sense that if we are able to aggressively control the chronic synovitis associated with rheumatoid arthritis with potent disease modifying agents such as biologics, we can essential prevent damage and destruction, which leads to arthroplasties.”

Hasan stressed that the societal price tag of RA must be balanced against the price of biologic DMARDs. “Indirect RA costs include loss of paid productivity at work, decreased quality of life, and higher rates of pain, depression, and anxiety,” she said, citing a large 2013 analysis of healthcare and payroll costs that calculated the annual incremental burden of RA to employers at $579 million in indirect costs and 4 million lost workdays. “These numbers speak for themselves. Although biologics are costly, their use is justified in order to improve the quality of life for patients with RA and to decrease the overall societal burden from this condition,” she said.

One limitation of the Danish study was the inherent risk of patient misclassification in registries. Furthermore, the decreased need for TKR among RA patients could have been due in part to increased use of treat-to-target strategies and more aggressive conventional synthetic DMARD combination therapy.

In addition, possible changes in diagnostic criteria for RA may have altered referral patterns of to orthopedic surgery. Increased focus on non-treatment factors such as obesity along with changes in the prevalence of certain comorbidities that would affect the use of joint replacement surgery around the time of bDMARD introduction might also have impacted the findings. “To investigate the true impact of bDMARDs on the need for joint surgery, studies using individual-level based information on DMARD treatment are needed,” the authors wrote.