Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials

Individual participant data systematic review and meta-analysis of three randomized, double-blind, placebo-controlled trials in adults with COPD. The pooled active intervention arms included 469 participants with IPD from studies conducted in Belgium, the United Kingdom, and the Netherlands, with varying disease severity and predominantly White European participants.

Oral vitamin D3 supplementation was tested in three randomized placebo-controlled COPD trials, with dosing regimens that differed by study: 100,000 IU monthly for 12 months, 120,000 IU every 2 months for 12 months, or 1200 IU daily for 6 months. The active regimens were compared with placebo.

Vitamin D supplementation did not reduce the overall rate of moderate or severe COPD exacerbations. In the pooled IPD analysis, the adjusted incidence rate ratio was 0.94 (95% CI 0.78 to 1.13; p=0.52), and the two-step analysis was similar at 0.94 (95% CI 0.79 to 1.12; p=0.51). A prespecified subgroup analysis showed benefit only in participants with baseline 25(OH)D <25 nmol/L, where the aIRR was 0.55 (95% CI 0.36 to 0.84; n=87; p=0.006), while those with baseline 25(OH)D ≥25 nmol/L had no effect (aIRR 1.04, 95% CI 0.85 to 1.27; p for interaction=0.015). No significant effects were seen for secondary lung function or exacerbation outcomes, and serious adverse events were not increased (adjusted OR 1.16, 95% CI 0.76 to 1.75).

Only three trials contributed IPD, with 469 participants overall and a much smaller vitamin D deficient subgroup, limiting precision and subgroup robustness. Dosing schedules and treatment durations varied across studies, and the population was predominantly White European, which may limit generalizability. The review also combined secondary and primary care populations with differing COPD severity and one trial of patients with prior COPD hospitalization, adding clinical heterogeneity. Not all outcomes were uniformly improved, and the apparent benefit was restricted to a prespecified low-baseline-vitamin-D subgroup rather than the overall population in this review.