A treat-to-target strategy targeting low disease activity remained achievable for some patients with late-onset rheumatoid arthritis and chronic lung disease, but comorbidities, treatment limitations, and serious adverse events complicated long-term implementation, according to findings from a prospective Japanese registry study.
The study included 197 methotrexate-naïve patients diagnosed with rheumatoid arthritis at age 60 years or older, including 47 with chronic lung disease (CLD) at baseline. Chronic lung disease included interstitial lung disease (ILD), emphysema, and airway disease. Researchers analyzed 5-year outcomes from the single-center CRANE registry in Japan.
Patients were treated using a treat-to-target (T2T) strategy targeting low disease activity. Methotrexate was used in patients with poor prognostic features, although tacrolimus could be substituted at physician discretion in patients with ILD. Biologic disease-modifying antirheumatic drugs (bDMARDs) were added in patients who did not respond by week 12 or failed to achieve low disease activity by week 24.
At 5 years, simplified disease activity index remission by nonresponder imputation occurred in 29.8% of patients with CLD and 44.0% of those without CLD. Functional status, defined as a Health Assessment Questionnaire Disability Index score of 0.5 or lower, was achieved in 36.2% and 45.3% of patients, respectively. Although these differences were not statistically significant, outcomes were consistently numerically worse among patients with CLD.
The study may have been underpowered to detect clinically meaningful differences between groups, given the relatively small CLD subgroup and substantial attrition over 5 years. Only 23 of 47 patients with CLD completed the full observation period, compared with 99 of 150 patients without CLD.
Patients with CLD also experienced more treatment-related limitations. Nonadherence to the T2T strategy because of comorbidities or adverse events occurred in 34.0% of patients with CLD, compared with 18.7% of those without CLD.
Safety differences were more pronounced. Serious adverse events of special interest occurred more frequently among patients with CLD, including infections requiring hospitalization, worsening extra-articular manifestations—primarily ILD deterioration—and fractures. In adjusted analyses, CLD was associated with a significantly higher risk for these events over 5 years (adjusted hazard ratio, 2.53; 95% CI, 1.60-4.00).
Among 31 patients with ILD at baseline, 10 experienced worsening disease during follow-up. Three patients later died after ILD exacerbation outside the formal observation period, and several others required transfer to long-term care facilities because of functional decline after high-dose glucocorticoid treatment.
The investigators noted that cumulative disease activity was significantly higher among patients whose ILD worsened, raising the possibility that tighter disease control earlier in treatment could influence pulmonary outcomes. However, the study was not designed to establish causality, and treatment selection varied according to physician discretion and baseline lung disease severity.
The findings should be interpreted cautiously. The study was observational, nonrandomized, and conducted at a single center, with a relatively small CLD subgroup. High-resolution computed tomography and pulmonary function testing were not performed uniformly, potentially leading to underrecognition of mild lung disease or ILD progression. Treatment decisions—including methotrexate avoidance and tacrolimus use in patients with ILD—also introduced potential indication bias.
“More evidence is required regarding the management of ILD and SAEs when implementing T2T for late-onset rheumatoid arthritis patients with CLD,” Manami Nomura, of the Institute of Science Tokyo, and colleagues wrote.
Funding came from Japanese government and rheumatology research grants. Several authors reported research funding, consulting relationships, speaker fees, or honoraria from pharmaceutical companies, while others reported no conflicts of interest.
Source: Arthritis Research & Therapy