Comparison of the Risk of Interstitial Lung Disease in Patients with RA with Biological and Targeted Disease-Modifying Antirheumatic Therapy

Purpose and Aim of the Study

Approximately 10% of RA patients develop clinically significant interstitial lung disease (ILD). The pathogenesis is not thoroughly explored, but risk factors include smoking, the positivity of rheumatoid factor or antibodies against cyclic citrullinated peptides, and variants of certain genes. When treating RA, a physician must choose a modality that keeps the patient's joint condition under control while having minimal potential toxic effects on lung tissue.

There is not yet enough data on the effect of biological therapy and targeted disease-modifying antirheumatic therapy (b/tsDMARD) on the development of ILD in RA patients. The aim of the cited nationwide retrospective study from the USA was to estimate the incidence of ILD in RA patients undergoing b/tsDMARD therapy and to compare the risk of ILD development with individual drugs versus the most commonly used tumor necrosis factor-alpha (TNF-α) inhibitor in RA treatment - adalimumab.

Analyzed Data and Patient Population

Data from the large American database Optum Clinformatics Data Mart Database from the period of December 1, 2003, to December 31, 2019, were used for the analysis. Individuals over 18 years old with a diagnosis of RA, who had been administered adalimumab, abatacept, rituximab, tocilizumab (the most commonly prescribed interleukin-6 inhibitor), or tofacitinib (the most commonly prescribed Janus kinase inhibitor) for at least 180 days (at least 2 doses of rituximab) were included.

Patients had to have records at least 1 year before the start of the evaluated therapy and could not have a pre-existing diagnosis of ILD. The primary parameter observed was the incidence of ILD. Included patients were followed until the discontinuation of the evaluated therapy + 90 days/+ 270 days for rituximab, the addition of new biological therapy, study termination, withdrawal from the study, or development of ILD.

Data from 28,559 RA patients with an average age of 56 years, of whom 78% were women, were analyzed. Adalimumab was administered to 13,326, abatacept to 5,676, rituximab to 5,444, tocilizumab to 2,548, and tofacitinib to 1,565 patients. The cohort with adalimumab was younger on average, more often male, had lower Charlson comorbidity scores, and more often concomitantly used methotrexate compared to other cohorts.

Results

During the follow-up, ILD newly developed in 276 patients (119 in the adalimumab cohort, 60 with abatacept, 62 with rituximab, 30 with tocilizumab, and 5 with tofacitinib). The crude incidence of ILD per 1,000 patient-years was 3.43 with adalimumab, 4.46 with abatacept, 6.15 with rituximab, 5.05 with tocilizumab, and 1.47 with tofacitinib. Treatment with tofacitinib resulted in a 69% lower likelihood of ILD development compared to adalimumab (adjusted hazard ratio [HR] 0.31; 95% confidence interval [CI] 0.12–0.78; p = 0.009). The likelihood of ILD development with tofacitinib was significantly lower than with other bDMARDs according to Kaplan-Meier analysis.

Cohorts of matched patients based on propensity score were created for the comparison of tofacitinib and adalimumab. These included 4,677 patients treated with adalimumab and 1,559 with tofacitinib. The average age of patients in these cohorts was 58 years, 83% were women, approximately 38% used methotrexate, and the average number of outpatient visits per year was 11. The incidence of ILD per 1,000 patient-years was 1.48 for patients with tofacitinib compared to 4.30 for patients with adalimumab. After adjusting for potential confounding factors, a 68% reduction in ILD risk was observed with tofacitinib compared to adalimumab (adjusted HR 0.32; 95% CI 0.13–0.82; p < 0.001).

Conclusion

In this retrospective cohort study with RA patients, a significant reduction in the risk of ILD development was observed with tofacitinib compared to adalimumab and other bDMARDs. The results suggest that treatment with tofacitinib, and possibly other Janus kinase inhibitors, may be beneficial in reducing the risk of ILD in RA patients.

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Source: Baker M. C., Liu Y., Lu R. et al. Incidence of interstitial lung disease in patients with rheumatoid arthritis treated with biologic and targeted synthetic disease-modifying antirheumatic drugs. JAMA Netw Open 2023 Mar 1; 6 (3): e233640, doi: 10.1001/jamanetworkopen.2023.3640.