Usual Care Without Antimicrobials sufficient for Patients with IPF: JAMA
Lung dysbiosis, observed as increased bacterial load and/or loss of diversity, has been reported in patients with idiopathic pulmonary fibrosis (IPF). It is usually associated with disease progression and a local and systemic immune response, potentially contributing to acute exacerbations, hospitalizations, and decreased survival.
In a recent study, researchers have reported that among adults with idiopathic pulmonary fibrosis, the addition of co-trimoxazole or doxycycline compared with usual care did not significantly improve the time to nonrespiratory hospitalization or death. The research has been published in the JAMA on May 11, 2021.
Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis. Previous randomized trial data suggested improved outcomes with co-trimoxazole (trimethoprim-sulfamethoxazole) therapy in patients with fibrosing interstitial lung diseases. However, a large placebo-controlled trial failed to document an improvement in clinical outcomes with this agent. To further evaluate this association, Dr Fernando J. Martinez and his team conducted a study and assessed the effect of antimicrobial therapy on clinical outcomes.
CleanUP-IPF was a pragmatic, randomized, unblinded clinical trial conducted across 35 US sites. The researchers included a total of 513 patients and randomly assigned them to receive antimicrobials (n = 254) or usual care alone (n = 259). Antimicrobials included co-trimoxazole (trimethoprim 160 mg/sulfamethoxazole 800 mg twice daily plus folic acid 5 mg daily, n = 128) or doxycycline (100 mg once daily if bodyweight <50 kg or 100 mg twice daily if ≥50 kg, n = 126). The major outcome assessed was time to first nonelective respiratory hospitalization or all-cause mortality.
Key findings of the study were:
- By the end of follow up at 13.1 months, the researchers identified 108 primary endpoint events.
- Among 108 events they noted that 52 events were reported on the usual care plus antimicrobial therapy group and 56 events on the usual care group, with no significant difference between groups (adjusted HR, 1.04).
- They found no statistically significant interaction between the effect of the prespecified antimicrobial agent (co-trimoxazole vs doxycycline) on the primary endpoint (adjusted HR, 1.15 in the co-trimoxazole group vs 0.82 in the doxycycline group).
- They reported 5% greater serious adverse events among those treated with usual care plus antimicrobials vs usual care alone included respiratory events (16.5% vs 10.0%).
- They also reported a higher number of infections (2.8% vs 6.6%); adverse events of special interest included diarrhoea (10.2% vs 3.1%) and rash (6.7% vs 0%) among the usual care plus antimicrobials than in usual care alone.
The authors concluded, "Among adults with idiopathic pulmonary fibrosis, the addition of co-trimoxazole or doxycycline to usual care, compared with usual care alone, did not significantly improve time to nonelective respiratory hospitalization or death. These findings do not support treatment with these antibiotics for the underlying disease."
For further information:
https://jamanetwork.com/journals/jama/article-abstract/2779827
