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Patients with rheumatoid arthritis (RA) who also had chronic obstructive pulmonary disease (COPD) had no increased risk of serious respiratory complications when treated with abatacept (Orencia), a large claims-based analysis found.
Compared with patients receiving other biologic agents, RA patients with COPD receiving abatacept were not at greater risk for an acute exacerbation of COPD requiring hospitalization, with a hazard ratio of 0.60 (95% CI 0.32-1.11), according to Samy Suissa, MD, of McGill University in Montreal, and colleagues.
Nor did the abatacept patients have an elevated risk for a combined endpoint of hospitalized COPD exacerbation, bronchitis, or hospitalized pneumonia/influenza, with an adjusted hazard ratio of 0.87 (95% CI 0.68-1.12), the researchers reported online in Seminars in Arthritis & Rheumatism.
"This paper was reassuring," said Mark Genovese, MD, of Stanford University in Palo Alto, California, who was not involved in the study. With regard to pulmonary events in patients receiving abatacept versus other biologic agents, the investigators "didn't find any real difference in a real-world population," he told MedPage Today.
The rationale for the study was an observation in a previous randomized trial known as ASSURE that serious respiratory events were reported more commonly among patients with RA and COPD on abatacept compared with placebo. That analysis included 37 patients receiving abatacept and 17 given placebo -- the abatacept product label cautions that "COPD patients may develop more frequent respiratory adverse events."
"This safety concern is important because it is estimated that close to 10% of RA patients also have COPD ... [and] it is uncertain whether these respiratory adverse events are more frequent than for other biologic disease-modifying antirheumatic drugs [DMARDs] in RA patients with COPD," Suissa and colleagues stated.
Accordingly, to explore these concerns in a larger, more representative population, the team analyzed outcomes from the Truven MarketScan and MarketScan Medicare databases in a study with a prevalent new-user design and matched time-conditional propensity scoring.
The cohort was selected from patients enrolled in those databases from 2007 through 2015, and included 1,807 patients with RA and COPD who initiated treatment with abatacept and 3,547 matched patients who started treatment with other biologics including etanercept (Enbrel), adalimumab (Humira), rituximab (Rituxan), and infliximab (Remicade). Mean follow-up was 235 days for abatacept and 171 days for other biologics.
Patients' mean age was 65, and almost three-quarters were women. Comorbidities such as hypertension, ischemic heart disease, and diabetes were common in both groups, as was the use of other medications such as oral and inhaled corticosteroids, antibiotics, DMARDs, and nonsteroidal anti-inflammatory drugs.
The incidence rates of severe COPD exacerbations were 1.2 per 100 per year for abatacept and 2.1 per 100 per year for other biologics. For bronchitis, the incidence rates were 4.2 and 5.3 per 100 per year for abatacept and other biologics, respectively.
For hospitalized pneumonia/influenza, the rates were 3.6 and 2.6 per 100 per year, respectively, and for outpatient pneumonia/influenza, the rates were 14.7 and 14.4 per 100 per year. For the combined endpoint of all events, the incidence rates were 8.7 for abatacept and 9.9 per 100 per year for other biologics.
Hazard ratios for events other than COPD exacerbations and the combined endpoint were as follows:
- Bronchitis, HR 0.80 (95% CI 0.56-1.14)
- Hospitalized pneumonia/influenza, HR 1.39 (95% CI 0.91-2.13)
- Outpatient pneumonia/influenza, HR 1.05 (95% CI 0.86-1.29
In discussing their findings, the authors noted that the ASSURE trial aimed to evaluate the safety of abatacept in RA in 959 patients on the active treatment and 482 on placebo. However, only 54 patients had concurrent COPD.
Serious respiratory events were reported in four patients in the abatacept group and none in the placebo group -- a difference of 11% versus 0%, which "is compatible with chance," Suissa and colleagues noted.
In contrast, "this large population-based comparative safety study in the real-world setting, which included over 1,800 patients with RA and COPD who initiated treatment with abatacept, showed that the risk of serious adverse respiratory events was not elevated compared with initiating treatment with other biologic DMARDs," the researchers concluded.
"I agree with the authors' conclusions," Genovese told MedPage Today.
Limitations of the study, the team said, included the observational design and the possibility of intrinsic biases and residual confounding.
The study was funded by the Canadian Foundation for Innovation and Bristol-Myers Squibb.
The authors reported financial relationships with Bristol-Myers Squibb, AstraZeneca, Bayer, Boehringer Ingelheim, and Novartis; two co-authors are employees of Bristol-Myers Squibb.