P3. Immunomodulatory agents

A Cochrane review of 36 studies published between 1981 and 2015 and involved 6192 participants with chronic bronchitis or COPD treated with either immunostimulants or placebo over a mean treatment period of 6 months (Fraser 2022) [evidence level I]. Participants treated with immunostimulants were slightly more likely to be free of exacerbations during the treatment period (OR 1.48, 95% CI 1.15 to 1.90; 15 RCTs, n=2961; I2 = 53%). Based on a mean estimate of baseline risk of 52%, 11 (95% CI 7 to 29) participants required treatment with an immunostimulant agent for one to be exacerbation‐free. Compared to placebo, fewer participants receiving immunostimulants required antibiotics during treatment (OR 0.34, 95% CI 0.18 to 0.63; 542 participants). The odds of experiencing an adverse event were similar between immunostimulant and placebo groups (OR 1.01, 95% CI 0.84 to 1.21; 20 RCTs, 3780 participants). Because there were so few events, the effect of immunostimulants on all-cause and respiratory-related mortality was unclear. The evidence assessed in this Cochrane review has several limitations. The agents used across studies were diverse, and detail about their purity and composition was limited, though the majority are designed to stimulate an immune response from bacterial products. The external validity of the study findings are uncertain, as only two of the 15 included trials were published in the last 10 years, and they will not reflect the current standards of practice. Furthermore, the reviewed population may not represent people with COPD according to our current definition, as included participants with chronic bronchitis who did not necessarily have airflow limitation, making it less generalisable to COPD. In conclusion, it is uncertain whether immunostimulants improve quality of life, and whether they are associated with reduced exacerbation risk and duration of respiratory-related hospitalisations in people with COPD. Further trials are needed to determine efficacy along with current recommended treatments.

The available evidence suggests that the putative immunomodulatory agent OM-85 BV is well tolerated (Sprenkle 2004) [evidence level I]. However, consistent results across important clinical outcomes, such as exacerbation and hospitalisation rates, are lacking to determine whether it is effective. Further randomised, controlled trials enrolling large numbers of persons with well-defined COPD are necessary to confirm the effectiveness of this agent.