Rheumatologist involvement often reclassifies interstitial lung disease
REPORTING FROM RWCS 2019
When to order a surgical lung biopsy
“If you’re pretty sure your patient had a CTD and then you get a characteristic HRCT and there are no exposures to account for the imaging findings – if we have a scenario where it all fits – we often don’t biopsy. Biopsy usually means a 2-night hospital stay, and it’s reportedly associated with about a 1% mortality risk. And the clinical reality is the biopsy may not impact treatment. They’re going to give you azathioprine, mycophenolate, cyclophosphamide, or prednisone for the ILD and the extrathoracic disease irrespective of the ILD pattern,” the rheumatologist said.
He reserves surgical biopsy for patients with an atypical HRCT, those with known CTD and a possible alternative etiology for the ILD, such as exposure to asbestos or owning pet birds, and patients where he’s just not sure a CTD is actually present.
Treatment of CTD-ILD
“The available controlled efficacy data are limited to scleroderma-ILD, where cyclophosphamide and mycophenolate work a little bit. And that’s it. We don’t have good data to guide us on which agent for which CTD or ILD pattern, for how long, or what dose,” Dr. Fischer said. “We have good drugs for the joints, nothing for the lungs. Treatment is not evidence based. We initiate with high-dose steroids, switch to a steroid-sparing agent, we evaluate the response to treatment with surveillance every 3-6 months by 6-minute walking, lung function tests, and sometimes imaging, and we treat for a long time. Oftentimes stability equals success.”
That being said, it must be emphasized that not all CTD-ILD warrants treatment of the pulmonary disease. If the patient’s ILD is mild and indolent, clinical surveillance is often appropriate, he continued.
More important than the pharmacotherapy available at present are adjunctive nonpharmacologic approaches: supplemental oxygen, pulmonary rehabilitation, treatment of comorbid GERD, immunizations, and addressing mental health issues related to these devastating diseases.
“We really don’t do these things well,” Dr. Fischer said.
On the horizon
An investigator-driven phase 2 clinical trial of the antifibrotic drug pirfenidone (Esbriet), now approved for IPF, is underway in patients with RA-ILD. Results of a trial of antifibrotic therapy in patients with scleroderma-ILD are due to be presented this year at EULAR. And a small study of antifibrotic therapy in patients with myositis-ILD is ongoing.
As for the biologics, there is a signal in the literature that tumor necrosis factor inhibitors may be associated with increased risk of rapidly progressive lung disease in patients with RA-ILD. An influential report from the British Society for Rheumatology Biologics Register on 299 patients with preexisting RA-ILD treated with anti-TNF therapy and 68 who received traditional disease-modifying antirrheumatic drugs showed that while mortality during follow-up was similar in the two groups, the proportion of deaths attributed to RA-ILD was 21% in the group on anti-TNF therapy, compared with only 7% in those on traditional DMARDs (Ann Rheum Dis. 2010 Jun;69[6]:1086-91).
Paul Emery, MD, rose from the audience at Dr. Fischer’s request to share his extensive experience with anti-TNF therapy and rituximab (Rituxan) in the setting of RA-ILD. When he was involved in several of the pivotal clinical trials of anti-TNF agents for RA he encountered a couple of cases of rapidly progressive ILD in patients on treatment.
“We had never before seen rapidly progressive ILD that didn’t respond to cyclophosphamide. Both patients died,” recalled Dr. Emery, professor of rheumatology and director of the University of Leeds (England) Musculoskeletal Biomedical Research Center.
“Our experience is if you’ve got mild ILD – and if you look hard enough you can find it in many rheumatoids – TNF inhibitor therapy doesn’t affect it. But if there’s any hint of deterioration we move away from anti-TNF therapy. Our preference has been for rituximab,” he said.
Dr. Emery was senior author of the largest study to date of rituximab in patients with RA-ILD (Rheumatology [Oxford]. 2017 Aug 1;56[8]:1348-57). While he and his coinvestigators concluded that rituximab “appears to be an acceptable therapeutic choice for patients with RA-ILD,” Dr. Fischer didn’t find persuasive evidence from this relatively small retrospective observational study in which only 44 patients had lung data available.
“My own conclusion is evidence is lacking to support a role of rituximab for treating ILD in RA,” Dr. Fischer said.
He reported receiving research grants from Boehringer-Ingelheim and Corbus and serving as a consultant to a handful of other pharmaceutical companies.
