Introduction
(Article introduction authored by Conquest Editorial Team)
Rheumatoid arthritis (RA) is an autoimmune-mediated inflammatory arthritis with a prevalence of 0.5–2%. RA patients may experience extra-articular complications like interstitial lung disease (ILD), cardiovascular disease, and osteoporosis, which contribute to increased mortality.
Various disease-modifying drugs are used for RA treatment, including conventional and biologic/targeted synthetic drugs. The KOBIO registry in South Korea collects real-world data on RA patients, offering insights into treatment outcomes.
This study from the KOBIO registry investigates the incidence of new-onset ILD in RA patients based on different drug types and explores factors influencing ILD occurrence, utilizing more than 10 years of data.
Patients and methods
The study utilized data from RA patients in the KOBIO registry (2012-2021), collected by the KCR. Inclusion criteria: RA patients aged >18, meeting 2010 ACR/EULAR criteria, and without ILD at enrollment.
Demographic, clinical, and medication data were collected at baseline, with follow-up annually. The study aimed to investigate new-onset ILD based on different drug types and identify factors influencing ILD occurrence. Statistical analyses, including Kaplan–Meier and Cox regression, were performed to assess ILD incidence. Data were analyzed using R software.
Results
Comparison of baseline characteristics between RA patients taking csDMARDs and b/tsDMARDs
A total of 2492 patients (1967 patients taking b/tsDMARDs and 525 patients taking csDMARDs) were included in the study. The flow chart showing the inclusion and exclusion process is presented in Figure 1.
Disease duration was longer, and the baseline ESR/CRP, DAS28, and SJC/TJC were higher, in the b/tsDMARDs group than in the csDMARDs group. In addition, radiographical evidence of erosion on the hands or feet was more common in the b/tsDMARDs group than in the csDMARDs group.
The most common b/tsDMARDs were TNFi (49.1%), whereas the use of MTX was similar between the two groups (84.6 versus 82.4%, respectively; p = 0.259). HCQ, SSZ, LEF, and TAC were used more frequently by the csDMARDs group than by the b/tsDMARDs group.
Incidence of ILD according to type of b/tsDMARDs and factors predictive of ILD in RA patients
The study had a mean follow-up duration of 5.2 years in the csDMARDs group and 4.2 years in the b/tsDMARDs group. Among the reported 30 new-onset ILD cases, two occurred in the csDMARDs group, 14 in the TNFi group, six each in the abatacept and tocilizumab groups, and none in the rituximab group. The ILD incidence rate was 0.07 per 100 person-years in the csDMARDs group and ranged from 0.29 to 0.61 per 100 person-years in the b/tsDMARDs groups. Kaplan–Meier analysis showed a higher probability of ILD occurrence in the TNFi, abatacept, and tocilizumab groups compared to the csDMARDs group. Univariate Cox regression identified factors like older age, male sex, higher DAS28, smoking history, RF titer, and TNFi or abatacept use as associated with increased HR for ILD. Air pollutant concentration and concurrent use of csDMARDs showed no association with ILD occurrence.
Discussion
The study investigates new-onset interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients using real-world data from the KOBIO registry. It identifies associations between various factors and ILD incidence, comparing csDMARDs and b/tsDMARDs groups. The incidence rates varied among b/tsDMARDs subgroups. Older age, male sex, higher time-averaged DAS28, and higher RF titer were associated with increased ILD risk. Notably, well-controlled disease activity contributed to ILD prevention. The study found no association between air pollutants and ILD in RA patients. The observational nature and limited ILD cases are acknowledged limitations. Further research with larger samples and controlled trials is recommended.
In conclusion, we compared the incidence of ILD in RA patients taking different b/tsDMARDs. We found that several factors (age, sex, time-averaged DAS28, and RF titer) were associated with an increased risk of ILD. ILD is an uncommon but potentially fatal complication in RA patients; therefore, RA patients at high risk of new-onset ILD should be monitored carefully.
References
1. Smolen JS, Aletaha D, Barton A, et al. Rheumatoid arthritis. Nat Rev Dis Primers 2018; 4: 18001.
2. KimH,SungY-K.EpidemiologyofrheumatoidarthritisinKorea.JRheumDis2021;28:60–67.
3. Lee H, Lee S-I, Kim H-O. Recent advances in basic and clinical aspects of rheumatoid arthritis-associated interstitial lung diseases. J Rheum Dis 2022; 29: 61–70.
4. LeeEE,ShinA,LeeJ,etal.All-causeandcause-specificmortalityofpatientswithrheumatoidarthritisinKorea:anation-widepopulation-basedstudy.JointBoneSpine2022; 89: 105269.
5. LeeY-K,BaeS-C.MortalityinKoreanpatientswithrheumatoidarthritis.JRheumDis2021;28:113–118.
6. Olson AL, Swigris JJ, Sprunger DB, et al. Rheumatoid arthritis-interstitial lung disease-associated mortality. Am J Respir Crit Care Med 2011; 183: 372–378.
7. NietoMA,Rodriguez-NietoMJ,Sanchez-PernauteO,etal.Mortalityrateinrheumatoidarthritis-relatedinterstitiallungdisease:theroleofradiographicpatterns.BMCPulm Med 2021; 21: 205.
8. Eun-Jung P, M.D, Hyungjin K, et al. The use of biological disease-modifying antirheumatic drugs for inflammatory arthritis in Korea: results of a Korean expert consensus. J Rheum Dis 2020; 27: 4–21.
9. Fraenkel L, Bathon JM, England BR, et al. 2021 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 2021; 73: 1108–1123.
10. Smolen JS, Landewé RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis 2023; 82: 3–18.
11. KimY,KimG-T.Positiveeffectsofbiologicsonosteoporosisinrheumatoidarthritis.JRheumDis2023;30:3–17.
12. ArtsEE,FransenJ,denBroederAA,etal.Theeffectofdiseasedurationanddiseaseactivityontheriskofcardiovasculardiseaseinrheumatoidarthritispatients.AnnRheum Dis 2015; 74: 998–1003.
13. Ozen G, Pedro S, Michaud K. The risk of cardiovascular events associated with disease-modifying antirheumatic drugs in rheumatoid arthritis. J Rheumatol 2021; 48: 648–655.
14. GulyásK,HorváthÁ,VéghE,etal.Effectsof1-yearanti-TNF-αtherapiesonbonemineraldensityandbonebiomarkersinrheumatoidarthritisandankylosingspondylitis. Clin Rheumatol 2020; 39: 167–175.
15. Nurmohamed MT, Heslinga M, Kitas GD. Cardiovascular comorbidity in rheumatic diseases. Nat Rev Rheumatol 2015; 11: 693–704.
16. Amarasekara DS, Yun H, Kim S, et al. Regulation of osteoclast differentiation by cytokine networks. Immune Netw 2018; 18: e8.
17. Kadura S, Raghu G. Rheumatoid arthritis-interstitial lung disease: manifestations and current concepts in pathogenesis and management. Eur Respir Rev 2021; 30: 210011. 18. Jani M, Hirani N, Matteson EL, et al. The safety of biologic therapies in RA-associated interstitial lung disease. Nat Rev Rheumatol 2014; 10: 284–294.
