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Higher Risk of Interstitial Lung Disease in Patients With RA, PsA Initiating bDMARDs

There were no differences in risk between patients with RA or PsA using or not using methotrexate.

Sella Aarrestad Provan, MD, PhD, Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway, Section of Public Health, Inland Norway University of Applied Sciences

Sella Aarrestad Provan, MD, PhD

Credit: Inland Norway University of Applied Sciences

Patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) initiating biologic disease-modifying antirheumatic drugs (bDMARD) had a higher risk of interstitial lung disease (ILD).1

"ILD is one of the most common pulmonary manifestations of RA, but its prevalence has not been investigated in PsA. The role of Methotrexate in ILD development remains debated. This study compares the incidences of ILD in patients with RA or PsA initiating a first bDMARD to that in the general population and investigates the role of methotrexate comedication on ILD incidence,” lead investigator Sella Aarrestad Provan, MD, PhD, Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway, Section of Public Health, Inland Norway University of Applied Sciences, and colleagues wrote.1

Provan and colleagues analyzed patients from 5 rheumatology registers and compared data with matched participants from the general population in 4 countries. They analyzed the incidence of ILD in 5 years of follow-up in patients with RA and PsA compared with the general population and for patients using methotrexate compared with those not.

The study included 29,487 patients with RA and 10,919 patients with PsA initiating a first bDMARD, as well as 362,087 participants from the general population. The investigators identified 225 cases of ILD in patients with RA, 23 cases in patients with PsA, and 251 in the general population cohort. Ater calculating hazard rates (HRs), Provan and colleagues found that patients with RA had an HR of 9.7 (95% CI, 8.0-11.9), patients with PsA had an HR of 4.4 (95% CI, 2.8-7.0) compared with the general population cohort. Patients that used methotrexate had an HR of 0.9 (95% CI, -.7-1.2) in the RA cohort and an HR of 1.0 (95% CI, 0.2-2.2) in the PsA cohort compared with those who did not use methotrexate.1

“To conclude, ILD occurs more frequently in patients with RA and PsA on bDMARDs than in the general population, especially in RA. In this treatment context, methotrexate is not a risk factor for ILD in the PsA population. In patients with RA who are treated with methotrexate co-medication we cannot exclude the possibility of an increased risk during the first 8 months of bDMARD therapy,” Provan and colleagues concluded.1

Other recent research with PsA elucidated factors associated with long-term opioid use in patients with PsA axial spondyloarthritis (AxSpA), including substance use disorder and a history of suicide or self-harm.2

The investigators found that being a current smoker (odds ratio [OR], 1.62 [95%CI, 1.38-1.90]), substance use disorder (OR, 2.34 [95%CI, 1.05-5.21]), history of suicide/self-harm (OR, 1.84 [95%CI, 1.13-2.99]), co-existing fibromyalgia (OR, 1.62 [95%CI, 1.11-2.37]), higher Charlson Comorbidity Index (OR, 3.61 [95%CI, 1.69-7.71] for high scores), high morphine milligram equivalent/day at initiation (OR, 1.03 [95%CI, 1.02-1.03]) and gabapentinoid (OR, 2.35 [95%CI, 1.75-3.16]) and antidepressant use (OR, 1.69 [95%CI, 1.45-1.98]) were associated with long-term opioid use. They also found that after comprehensive adjustment, socioeconomic deprivation was associated with an incrementally higher risk of long-term opioid use.2

On the other hand, being female (OR=0.83, 95% CI=0.74, 0.95), taking benzodiazepines (OR=0.79, 95% CI=0.63, 0.98), and being mixed or non-white ethnicity (OR=0.55, 95% CI=0.37, 0.82) was associated with a reduced risk of long-term opioid use only seen in patients with PsA.2

REFERENCES
1. Provan SA, Ljung L, Kristianslund EK, et al. Interstitial lung disease in rheumatoid or psoriatic arthritis patients initiating biologics, and controls - data from five Nordic registries. J Rheumatol. 2024; 51(9) doi: 10.3899/jrheum.2024-0252
2. Huang YT, Jenkins DA, Yimer BB, Jani M. Factors associated with long-term opioid use among patients with axial spondyloarthritis or psoriatic arthritis who initiated opioids. Rheumatol. Published online August 16, 2024; keae444.doi: 10.1093/rheumatology/keae444
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