Patients with RA Face Increased ILD Risk with Biologic Therapy

Sella Aarrestad Provan, MD, PhD

Results of a recent study revealed patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) who began treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) had a higher risk of developing interstitial lung disease (ILD) compared with the general population, with RA patients being at the greatest risk.

Interestingly, although the role of methotrexate in the development of ILD continues to be the subject of debate, the study found co-therapy with methotrexate did not significantly influence the likelihood of ILD in either condition.

Despite ILD being identified as one of the most common pulmonary manifestations of RA, with clinical estimations ranging from approximately 2 – 15%, its prevalence in PsA remains a mystery.

“Data on ILD in patients with PsA is scarce,” wrote a team of investigators led by Sella Aarrestad Provan, MD, PhD, Senior physician in rheumatology at the Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway. “Although comorbidities of PsA are increasingly recognized, ILD is not mentioned as a comorbidity that the clinician should be aware of in neither the PsA treatment recommendations. However, several ILD case reports have been published in patients with PsA and psoriasis.”

To compare the incidences of ILD in patients with these rheumatic conditions initiating a bDMARD with the general population, investigators conducted a large real-world observational study that recruited participants from five Nordic rheumatology registers. Information on demographics, disease activity and methotrexate prescription were collected. These patients were then matched with a group of controls from four countries using National Population Registers data.

Baseline disease activity among patients was evaluated using the Disease Activity Score for 28-joint count with CRP (DAS28-CRP). Other information collected included rheumatoid factor (RF) status, smoking habits, disease duration, self-reported physical function in the Health Assessment Questionnaire (HAQ), information on anticitrullinated protein antibodies (ACPA), and both the physician’s and patient’s global assessment of disease activity on a 100 mm Visual Analog Scale (VAS).

Incidence of ILD was assessed for a five-year follow-up period and rates were assessed among patients compared with the general population as well as among methotrexate users compared with non-users.

Ultimately, 29,478 patients with RA and 10,919 patients with PsA were included in the study, along with 362,087 controls. Over half (59%, 52% and 57%, respectively) of subjects completed the full 5 years of observation.

During the follow-up period, 225 patients with RA, 23 patients with PsA and 251 controls were diagnosed with ILD. The hazard ratios for ILD compared with the general population were higher in patients with RA (9.7 vs 4.4, respectively); however, hazard ratios for ILD for those receiving concurrent methotrexate were comparable among patient groups (0.9 vs 1.0, respectively).

No significant differences were observed between the initiation of a bDMARD and an ILD diagnosis between patients with RA and PsA (mean time 1.9 years for both). Patients with RA who developed the lung disease were older, more likely to be male and had higher disease activity. Patients with PsA and ILD were also older, had higher patient VAS at baseline and higher levels of erythrocyte sedimentation rate (ESR).

The large and heterogeneous international patient population strengthened the study, despite limitations including the lack of classification or diagnostic criteria for ILD in patients with rheumatic diseases.

“In patients with RA who are treated with methotrexate co-medication we cannot exclude the possibility of an increased risk during the first eight months of bDMARD therapy,” investigators concluded.