Mortality in rheumatoid arthritis patients with pulmonary nontuberculous mycobacterial disease: A retrospective cohort study

Abstract

Objective: The aim of this study was to compare long-term mortality following diagnosis of pulmonary nontuberculous mycobacterial (NTM) disease between patients with and without rheumatoid arthritis (RA) and to evaluate predictive factors for death outcomes.

Methods: We reviewed the electronic medical records of all patients who were newly diagnosed with pulmonary NTM disease at participating institutions between August 2009 and December 2018. Patients were followed until death, loss to follow-up, or the end of the study. Taking into consideration the presence of competing risks, we used the cumulative incidence function with Gray's test and Fine-Gray regression analysis for survival analysis.

Results: A total of 225 patients (34 RA patients and 191 non-RA controls) were followed, with a mean time of 47.5 months. Death occurred in 35.3% of RA patients and 25.7% of non-RA patients. An exacerbation of pulmonary NTM disease represented the major cause of death. The estimated cumulative incidence of all-cause death at 5 years was 24% for RA patients and 23% for non-RA patients. For NTM-related death, the 5-year cumulative incidence rate was estimated to be 11% for RA patients and 18% for non-RA patients. Gray's test revealed that long-term mortality estimates were not significantly different between patient groups. Fine-Gray regression analysis showed that the predictive factors for NTM-related death were advanced age (adjusted hazards ratio 7.28 [95% confidence interval 2.91-18.20] for ≥80 years and 3.68 [1.46-9.26] for 70-80 years vs. <70 years), male sex (2.40 [1.29-4.45]), Mycobacterium abscessus complex (4.30 [1.46-12.69] vs. M. avium), and cavitary disease (4.08 [1.70-9.80]).

Conclusions: RA patients with pulmonary NTM disease were not at greater risk of long-term mortality compared with non-RA patients. Rather, advanced age, male sex, causative NTM species, and cavitary NTM disease should be considered when predicting the outcomes of RA patients with pulmonary NTM disease.

Fig 1. Cumulative incidence of NTM-related death and all-cause death in RA and non-RA patients.

Using the CIF, the cumulative incidence of NTM-related death (A) and all-cause death (B) in patients who were newly given a diagnosis of pulmonary NTM disease is shown in the RA and non-RA groups. Numbers below these figures represent the number of patients at risk. The cumulative incidence of death over time between both groups was compared using Gray’s test. According to univariate Fine-Gray analyses, the unadjusted HR (95% CI) of RA versus non-RA was 0.86 (0.38–1.98, p = 0.73) for NTM-related death and 1.34 (0.75–2.40, p = 0.32) for all-cause death. RA, rheumatoid arthritis; NTM, nontuberculous mycobacterial disease; CIF, cumulative incidence function; HR, hazard ratio; CI, confidence interval.

Fig 2. HRCT scans of a patient with the cavitary NB form (case 5).

(A) An HRCT scan taken at the time of diagnosis of pulmonary NTM disease. Nodules and ground-glass opacities are evident in both lungs. Consolidation is evident in the right middle lobe (S4). In addition, bronchiectasis, the tree-in-bud sign, and cavitary lesions are evident in the lingular segment of the left upper lobe (S4). (B) An HRCT scan taken 8 months before the patient died. Extensive nodular opacities are evident in both lungs. Bronchiectasis, the tree-in-bud sign, and cavitary lesions are prominent in the right middle lobe, the lingular, and the left lower lobe.

Fig 3. Cumulative incidence of NTM-related death grouped by predictive factors.

Using the CIF, the cumulative incidence of NTM-related death in patients who were newly diagnosed with pulmonary NTM disease is shown grouped according to predictive factors for death. Predictive factors included (A) age (≥80 years and 70–80 years vs. <70 years), (B) sex (male vs. female), (C) NTM species (M. abscessus complex [Mab] and M. intracellulare vs. M. avium), and (D) HRCT patterns (cavitary NB/fibrocavitary form and unclassifiable form vs. non-cavitary NB form). Numbers below these figures represent the number of patients at risk. The cumulative incidence of death over time between groups with and without predictive factors was compared using Gray’s test with or without the post hoc Holm’s procedure. NTM, nontuberculous mycobacterial disease; Mab, M. abscessus complex; NB, nodular bronchiectatic form; FC form, fibrocavitary form; CIF, cumulative incidence function.