Systematic review and meta-analysis of prognostic factors for idiopathic inflammatory myopathy-associated interstitial lung disease

Abstract

Objective: To clarify prognostic factors for idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD).

Design: Systematic review and meta-analysis using the Grades of Recommendation, Assessment, Development and Evaluation system.

Data sources: Medline, EMBASE and Science Citation Index Expanded were searched through 9 August 2018.

Eligibility criteria for selecting studies: The review includes primary studies addressing all-cause mortality of IIM-associated ILD. Potential prognostic factors were any clinical information related to the outcome.

Data extraction and synthesis: Two reviewers extracted relevant data independently and assessed risk of bias using the Quality in Prognostic Studies tool. Meta-analysis was conducted using a random effects model and if inappropriate the results were reported qualitatively. Prognostic factors were determined based on statistically significant results derived from multivariate analysis.

Results: Of a total of 5892 articles returned, 32 were deemed eligible for analysis and cumulatively, these studies reported 28 potential prognostic factors for all-cause mortality. Each study was subject to certain methodological constraints. The four prognostic factors, which demonstrated statistically significant results on both univariate and multivariate analyses, were as follows: age (MD 5.90, 3.17-8.63/HR 1.06, 1.02-1.10 and 2.31, 1.06-5.06), acute/subacute interstitial pneumonia (A/SIP) (OR 4.85, 2.81-8.37/HR 4.23, 1.69-12.09 and 5.17, 1.94-13.49), percentage of predicted forced vital capacity (%FVC) (OR 0.96, 0.95-0.98/HR 0.96, 0.93-0.99) and anti-Jo-1 antibody (OR 0.35, 0.18-0.71/HR 0.004, 0.00003-0.54) (univariate/multivariate, 95% CI). Other prognostic factors included ground glass opacity/attenuation (GGO/GGA) and extent of radiological abnormality. The quality of the presented evidence was rated as either low or very low.

Conclusions: Older age, A/SIP, lower value of %FVC, GGO/GGA and extent of radiological abnormality were demonstrated to predict poor prognosis for IIM-associated ILD while a positive test for anti-Jo-1 antibody indicated better prognosis. However, given the weak evidence they should be interpreted with caution.

Trial registration number: CRD42016036999.

Keywords: idiopathic inflammatory myopathy; interstitial lung disease; meta-analysis; prognosis; systematic review.

Figure 1

Forest plot of the result of univariate analysis for age. Nine studies were pooled for meta-analysis and a total of 267 patients with 22 of polymyositis, 126 of dermatomyositis, 93 of clinically amyopathic dermatomyositis (CADM) and 26 of polymyositis or dermatomyositis were included. Non-survivors were significantly older than survivors with the mean difference (MD) of 5.90 years (95% CI 3.17 to 8.63, p<0.0001) and there was no heterogeneity (Χ²=3.20, p=0.92, I²=0%).

Figure 2

Forest plot of the result of univariate analysis for acute/subacute interstitial pneumonia (A/SIP). Ten studies were pooled for meta-analysis and a total of 460 patients with 48 of polymyositis, 223 of dermatomyositis, 156 of clinically amyopathic dermatomyositis (CADM) and 33 of polymyositis or dermatomyositis were included. There was a significant difference of all-cause mortality between A/SIP and chronic IP with the OR of 4.85 (95% CI 2.81 to 8.37, p<0.00001). A point estimate of individual studies was all in the same direction although substantial heterogeneity was identified (Χ²=19.50, p=0.02, I²=54%). The 95% prediction interval was between 0.80 and 29.40.

Figure 3

Forest plot of the result of univariate analysis for forced vital capacity of predicted (%FVC). Four studies were pooled for meta-analysis and a total of 245 patients with 41 of polymyositis, 63 of dermatomyositis, 98 of clinically amyopathic dermatomyositis (CADM) and 43 of antisynthetase syndrome (ASS) were included. %FVC was significantly associated with all-cause mortality with the OR of 0.96 (95% CI 0.95 to 0.98, p<0.0001). A point estimate of individual studies was all in the same direction although not important heterogeneity was identified (Χ²=3.13, p=0.37, I²=4%). The 95% prediction interval was between 0.92 and 0.99.

Figure 4

Forest plot of the result of univariate analysis for anti-Jo-1 antibody. Six studies were pooled for meta-analysis and a total of 403 patients with 30 of polymyositis, 162 of dermatomyositis, 54 of clinically amyopathic dermatomyositis (CADM), 43 of antisynthetase syndrome (ASS) and 114 of polymyositis, dermatomyositis and CADM were included. Anti-Jo-1 antibody was significantly protective against all-cause mortality with the OR of 0.35 (95% CI 0.18 to 0.71, p=0.003). There was no heterogeneity (Χ²=2.42, p=0.79, I²=0%).