European League Against Rheumatism06.15.18
The results of two studies presented today at the Annual European Congress of Rheumatology (EULAR 2018) investigate joint replacement procedures in rheumatoid arthritis (RA) patients.1,2 The first study demonstrates that joint replacement procedures have significantly reduced in RA patients in the past decade1 and the second investigates the impact of biologic therapies on this change using the British Society for Rheumatology Biologics Registry for Rheumatoid Arthritis (BSRBR/RA).2
"We welcome these results demonstrating such a dramatic reduction of joint replacements in RA patients in recent years," said Professor Robert Landewé, Chairperson of the Scientific Programme Committee, EULAR. "It's also very interesting to see data relating specifically to the impact of biological treatments on this outcome given the breadth of progress in the management of RA over the same time period."
Joint Replacement Surgery Halved in Rheumatoid Arthritis Patients Between 1997-2010.1
The retrospective cohort study examined data from around one million people between 1997 and 2010 using administrative healthcare data. Results demonstrate a striking reduction of 51.9 percent (p<0.001) in joint replacement surgery in RA patients between 1997 and 2010.1
The number of joint replacements in matched controls increased by 31.9 percent (p=0.002) over the 13 years, although remained significantly less than in RA patients at both time points (4.78 percent vs. 0.47 percent in 1997 and 2.30 percent vs. 0.62 percent in 2010). Rates of cardiac interventions did not change significantly over time in either group suggesting the changes observed in joint replacement surgery were due to improvements in the treatment of RA rather than access to surgical procedures.1
"Literature to date has reported inconsistent findings," said Dr. John Hanly, Professor of Medicine (Rheumatology) and Pathology at Dalhousie University and attending staff rheumatologist at the Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, Canada. "However, our results add significant evidence to show a clear reduction in joint replacement surgery in RA patients, most likely due to improvements in medical management over the last few decades."
Cases of RA were identified using a method previously validated in the same data set.3 Each case was matched by age and gender to four randomly selected controls. The number of RA cases increased from 3,913 (0.42 percent) to 4,911 (0.52 percent) over the study, the mean age changed from 56.7 to 60.1 years and the proportion of females from 70.8 to 73.9 percent. Annual frequency of joint replacement surgery as well as coronary artery interventions was compared.1
Impact of Biological Therapy on Rate of Joint Replacement Procedures.2
The management of RA has progressed significantly over the last 25 years from providing relief of symptoms to regimens that impact disease activity.4 This evolution has been multi-factorial, however it is widely recognized that the introduction of biological therapy with tumor necrosis factor inhibitors (TNFi) in the late 1990s revolutionized treatment.4,5,6,7 Furthermore, recent research from the UK and Denmark has demonstrated a decline in the incidence of joint replacements for RA patients directly following the introduction of TNFi.8,9 However, findings presented today suggest that, although TNFi use may reduce the need for total hip replacement (THR) in older and more severe RA patients, no association was found in younger or less severe patients. Neither was there an association in rates of total knee replacement (TKR) or other joint replacement.2
"The use of biologic therapies has been routinely offered as an explanatory factor for the reduction in rates of joint replacement over recent years," said Samuel Hawley, University of Oxford. "Our study offers some support for this in that a reduction in hip replacement procedures was observed in older patients on TNFi, although our results also suggest additional factors are likely to be involved. For example, the drive for earlier diagnosis/treatment and increased prescription rates of conventional synthetic disease-modifying antirheumatic drugs. It's important to highlight that we used an observational study design and that despite our best efforts to address confounding factors, these may still partly explain our findings".
The study analyzed the differences between RA patients who were TNFi or conventional synthetic disease-modifying antirheumatic drug (csDMARD) users in a 1:1 propensity score matched cohort of 19,116 patient records using the BSRBR/RA data. In the full study population, investigators found no significant association between TNFi use and THR or TKR. However, there was a significant reduction of THR by 40 percent in those over 60 years taking TNFi (HR 0.60 [CI:0.41-0.87]) and THR rate was cut by a quarter in TNFi users when analyses were restricted to more severe patients (DAS>5.1), although this didn't reach significance (HR 0.74 [CI 0.51-1.05]). No significant findings were found relating TNFi users with TKR procedures.2
References
1 Hanly JG, Lethbridge L, Skedgel C. Change in frequency of arthroplasty surgery in rheumatoid arthritis: A 13 year population health study. EULAR 2018; Amsterdam: Abstract SAT0077.
2 Hawley S, Cordtz R, Dreyer L, et al. Impact of TNF inhibitors on need for joint replacement in patients with rheumatoid arthritis: A matched cohort analysis of UK biologics registry data. EULAR 2018; Amsterdam: Abstract OP0116.
3 Hanly JG, Thompson K, Skedgel C. The use of administrative healthcare databases to identify patients with Rheumatoid Arthritis. Open Access Rheumatol. 2015;7:69-75.
4 Upchurch KS, Kay J. Evolution of treatment for rheumatoid arthritis. Rheumatology (Oxford). 2012;51(suppl 6):vi28-36.
5 Scott DL. Biologics-based therapy for the treatment of rheumatoid arthritis. Clin Pharmacol Ther. 2012;91(1):30-43.
6 Feldmann M, Williams RO, and Paleolog E. What have we learnt from targeted anti-TNF therapy? Ann Rheum Dis. 2010;69:97-9.
7 Curtis JR and Singh JA. Use of biologics in rheumatoid arthritis: current and emerging paradigms of care. Clin Ther. 2011;33:679-707.
8 Cordtz RL, Hawley S, Prieto-Alhambra D, et al. Incidence of hip and knee replacement in patients with rheumatoid arthritis following the introduction of biological DMARDs: an interrupted time-series analysis using nationwide Danish healthcare registers. Ann Rheum Dis. 2018;77(5):684-9.
9 Hawley S, Cordtz R, Dreyer L, et al. Association between NICE guidance on biologic therapies with rates of hip and knee replacement among rheumatoid arthritis patients in England and Wales: An interrupted time-series analysis. Semin Arthritis Rheum. 2018;47(5):605-10.
"We welcome these results demonstrating such a dramatic reduction of joint replacements in RA patients in recent years," said Professor Robert Landewé, Chairperson of the Scientific Programme Committee, EULAR. "It's also very interesting to see data relating specifically to the impact of biological treatments on this outcome given the breadth of progress in the management of RA over the same time period."
Joint Replacement Surgery Halved in Rheumatoid Arthritis Patients Between 1997-2010.1
The retrospective cohort study examined data from around one million people between 1997 and 2010 using administrative healthcare data. Results demonstrate a striking reduction of 51.9 percent (p<0.001) in joint replacement surgery in RA patients between 1997 and 2010.1
The number of joint replacements in matched controls increased by 31.9 percent (p=0.002) over the 13 years, although remained significantly less than in RA patients at both time points (4.78 percent vs. 0.47 percent in 1997 and 2.30 percent vs. 0.62 percent in 2010). Rates of cardiac interventions did not change significantly over time in either group suggesting the changes observed in joint replacement surgery were due to improvements in the treatment of RA rather than access to surgical procedures.1
"Literature to date has reported inconsistent findings," said Dr. John Hanly, Professor of Medicine (Rheumatology) and Pathology at Dalhousie University and attending staff rheumatologist at the Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, Canada. "However, our results add significant evidence to show a clear reduction in joint replacement surgery in RA patients, most likely due to improvements in medical management over the last few decades."
Cases of RA were identified using a method previously validated in the same data set.3 Each case was matched by age and gender to four randomly selected controls. The number of RA cases increased from 3,913 (0.42 percent) to 4,911 (0.52 percent) over the study, the mean age changed from 56.7 to 60.1 years and the proportion of females from 70.8 to 73.9 percent. Annual frequency of joint replacement surgery as well as coronary artery interventions was compared.1
Impact of Biological Therapy on Rate of Joint Replacement Procedures.2
The management of RA has progressed significantly over the last 25 years from providing relief of symptoms to regimens that impact disease activity.4 This evolution has been multi-factorial, however it is widely recognized that the introduction of biological therapy with tumor necrosis factor inhibitors (TNFi) in the late 1990s revolutionized treatment.4,5,6,7 Furthermore, recent research from the UK and Denmark has demonstrated a decline in the incidence of joint replacements for RA patients directly following the introduction of TNFi.8,9 However, findings presented today suggest that, although TNFi use may reduce the need for total hip replacement (THR) in older and more severe RA patients, no association was found in younger or less severe patients. Neither was there an association in rates of total knee replacement (TKR) or other joint replacement.2
"The use of biologic therapies has been routinely offered as an explanatory factor for the reduction in rates of joint replacement over recent years," said Samuel Hawley, University of Oxford. "Our study offers some support for this in that a reduction in hip replacement procedures was observed in older patients on TNFi, although our results also suggest additional factors are likely to be involved. For example, the drive for earlier diagnosis/treatment and increased prescription rates of conventional synthetic disease-modifying antirheumatic drugs. It's important to highlight that we used an observational study design and that despite our best efforts to address confounding factors, these may still partly explain our findings".
The study analyzed the differences between RA patients who were TNFi or conventional synthetic disease-modifying antirheumatic drug (csDMARD) users in a 1:1 propensity score matched cohort of 19,116 patient records using the BSRBR/RA data. In the full study population, investigators found no significant association between TNFi use and THR or TKR. However, there was a significant reduction of THR by 40 percent in those over 60 years taking TNFi (HR 0.60 [CI:0.41-0.87]) and THR rate was cut by a quarter in TNFi users when analyses were restricted to more severe patients (DAS>5.1), although this didn't reach significance (HR 0.74 [CI 0.51-1.05]). No significant findings were found relating TNFi users with TKR procedures.2
References
1 Hanly JG, Lethbridge L, Skedgel C. Change in frequency of arthroplasty surgery in rheumatoid arthritis: A 13 year population health study. EULAR 2018; Amsterdam: Abstract SAT0077.
2 Hawley S, Cordtz R, Dreyer L, et al. Impact of TNF inhibitors on need for joint replacement in patients with rheumatoid arthritis: A matched cohort analysis of UK biologics registry data. EULAR 2018; Amsterdam: Abstract OP0116.
3 Hanly JG, Thompson K, Skedgel C. The use of administrative healthcare databases to identify patients with Rheumatoid Arthritis. Open Access Rheumatol. 2015;7:69-75.
4 Upchurch KS, Kay J. Evolution of treatment for rheumatoid arthritis. Rheumatology (Oxford). 2012;51(suppl 6):vi28-36.
5 Scott DL. Biologics-based therapy for the treatment of rheumatoid arthritis. Clin Pharmacol Ther. 2012;91(1):30-43.
6 Feldmann M, Williams RO, and Paleolog E. What have we learnt from targeted anti-TNF therapy? Ann Rheum Dis. 2010;69:97-9.
7 Curtis JR and Singh JA. Use of biologics in rheumatoid arthritis: current and emerging paradigms of care. Clin Ther. 2011;33:679-707.
8 Cordtz RL, Hawley S, Prieto-Alhambra D, et al. Incidence of hip and knee replacement in patients with rheumatoid arthritis following the introduction of biological DMARDs: an interrupted time-series analysis using nationwide Danish healthcare registers. Ann Rheum Dis. 2018;77(5):684-9.
9 Hawley S, Cordtz R, Dreyer L, et al. Association between NICE guidance on biologic therapies with rates of hip and knee replacement among rheumatoid arthritis patients in England and Wales: An interrupted time-series analysis. Semin Arthritis Rheum. 2018;47(5):605-10.
