Acute Exacerbations Common and Often Fatal in RA-ILD

Pam Harrison

July 06, 2022

Acute exacerbations (AEs) are both common in rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and are a frequent cause of imminent mortality, a retrospective Japanese study suggests.

The same is also true for patients with idiopathic pulmonary fibrosis (IPF) for whom an AE is the most frequent cause of death as well, the same comparative study indicates.

“Several studies have reported that acute exacerbation, which occurs during the clinical course of idiopathic pulmonary fibrosis (IPF), also occurs in rheumatoid arthritis–associated interstitial lung disease (RA-ILD),” lead author Junji Otsuka, MD, PhD, of the National Hospital Organization Omuta National Hospital, Fukuoka, Japan, and colleagues observed.

“[We found that] AE was not uncommon in RA-ILD or IPF ... but the prognosis after AE of RA-ILD was significantly better than that of IPF [even though] the most frequent cause of death in RA-ILD and IPF was AE,” they stated.

The study was published online in Respiratory Medicine.

Patient Features

The study involved 149 RA-ILD patients with a median age of 72 years at RA onset. The median time from ILD diagnosis to onset of AE was 48.5 months, while the median survival time after the onset of AE was 196 days (range 1-3,463 days), as the authors detailed. “All patients were treated with corticosteroids,” the authors noted, and almost all of them were treated with steroid pulse therapy.

Noninvasive positive pressure ventilation (NPPV) was used to maintain oxygenation in 18.5% of patients with severe respiratory failure, while invasive positive pressure ventilation (IPPV) was used in almost 26% of patients with the same degree of respiratory failure. Features of patients who developed an AE were then compared with those who did not.

Interestingly, no significant differences in clinical parameters were seen between those who developed an AE and those who did not. Nor were there any significant differences between the 2 groups in the length of time from the ILD diagnosis to the development of an AE. Some 18% of RA-ILD patients developed an AE, as did over 27% of patients with IPF, investigators report.

The median survival after RA-ILD patients developed an AE was 277 days, compared with only 60 days for those with IPF (P = .038). In a multivariable analysis, hypoalbuminemia at an odds ratio of .090 (95% confidence interval, 0.011-0.733; P = .012) as well as percent carbon monoxide diffusion capacity at an OR of .810 (95% CI, 0.814-0.964; P < .01) were both independent risk factors for the development of an AE, the investigators pointed out.

The best cut-off level for predicting the risk of an AE was 3.0 g/dL (95% CI, 0.011-0.733; P = .012) for serum albumin and 53% (95% CI, 0.814-0.964; P < .01) for carbon monoxide diffusion capacity. As Otsuka noted in an email to this news organization, low serum albumin likely correlates with a generally poor condition, while low carbon monoxide diffusion capacity is likely due to lung fibrosis.

“But if low albumin and low carbon monoxide diffusion capacity are due to the progression of ILD, both values may be difficult to improve,” he added.

Survivors Versus Nonsurvivors

Of those patients with RA-ILD who developed an AE, approximately half recovered. Among the IPF patients who developed an AE during the study period, approximately 39% recovered from the event, while 70% did not. Comparing RA-ILD patients who survived versus whose who did not, again, no significant demographic or clinical differences were seen between the 2 groups. On the other hand, the number of patients treated with immunosuppressants for their AE was significantly higher among patients who did not survive the AE, compared with those who did (P =.022), investigators note.

Similarly, the number of patients who required NPPV was also significantly higher among those who did not survive, compared with those who did. In fact, “none of the surviving patients used NPPV (P <0.01),” the authors stress. The number of patients who required IPPV was also significantly higher among nonsurvivors than among survivors (P =.017), and of the small number of patients who were treated with IPPV, all but one died without recovery.

As the authors suggested, these findings suggest that RA-ILD patients who recover from an AE with the help of corticosteroids alone have a relatively decent prognosis. In contrast, those who require immunosuppressive drugs in addition to steroids or mechanical ventilation for AE management can be expected to have a poor prognosis.

The same can also be said for IPF patients and even with the help of mechanical ventilation “with IPF patients, the survival rate is low anyway, so the indication for mechanical ventilation should be carefully judged,” Otsuka stressed.

Cause of Death

The authors also compared the cause of death between patients with RA-ILD and those with IPF. “In RA-ILD patients, the most frequent cause of death was AE,” they report, at close to 35% of all patients with RA-ILD. This was also true for IPF patients among whom AE was the cause of death for over 44%. “These results indicate that, as in IPF, AE develops in the clinical course of RA-ILD with considerable frequency,” investigators note.

“During the clinical course of RA-ILD, as with IPD, it is necessary to pay attention to AE,” they stress. Otsuka added: “It may be difficult to change the prognosis of these patients.”

“However, knowing which patients are more likely to develop AE may help predict the prognosis, and it may be improved if antifibrotic agents are used for these patients,” he said. Elizabeth Volkmann, MD, director, UCLA scleroderma program, University of California, Los Angeles, felt that understanding the risk factors for AEs in this patient population may help physicians identify a subgroup of patients with RA-ILD who require closer monitoring and follow-up.

“These patients may also require more aggressive treatment for RA-ILD to prevent AEs,” she said in an email to this news organization. Given that the study was retrospective in nature, Volkmann cautioned that there were likely multiple confounding factors that could have affected survival in this patient population and not to take away from the study that survival was solely affected by immunosuppressant use, for example.

“It is possible that patients [treated with] immunosuppressants had other features of their disease that independently heightened their risk of mortality,” Volkmann said. Similarly, physicians should not assume that the high mortality rate seen in RA-ILD patients who were treated with mechanical ventilation had anything to do with mechanical ventilation itself, as patients requiring ventilation are likely to have worse outcomes, as she stressed.

As for hypoalbuminemia, Volkmann pointed out that hypoalbuminemia is often a sign of malnutrition in these patients. “Studies have demonstrated that malnutrition is an independent predictor of mortality in patients with ILD,” she emphasized.

“Optimizing patients’ nutritional status could potentially help lower the risk of AEs,” Volkmann suggested.

Limitations of the study include the fact that it was a single-center design study and included only a limited number of patients.

No specific funding source was noted. The authors have no conflicts of interest to declare.

This story originally appeared on, part of the Medscape Professional Network.


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