Limitations
The small sample size, resulting from the strict exclusion criteria, limits the generalizability of the results. Although the low number of events seen in this study supports safety in ICS discontinuation, there may have been higher rates observed in a larger population. The most common reason for patient exclusion was the initiation of another ICS immediately following discontinuation of the original ICS. During the study period, VANTHCS underwent a change to its formulary: Fluticasone/salmeterol replaced budesonide/formoterol as the preferred ICS/LABA combination. As a result, many patients had their budesonide/formoterol discontinued during the study period solely to initiate fluticasone/salmeterol therapy. As these patients did not truly have their ICS discontinued or have a significant period without ICS therapy, they were not included in the results, and the total patient population available to analyze was relatively limited.
The low event rate also limits the ability to compare various factors influencing exacerbation risk, particularly taper vs abrupt ICS discontinuation. This is further compounded by the small number of patients who had a taper performed and the lack of consistency in the method of tapering used. Statistical significance could not be determined for any outcome, and all findings were purely hypothesis generating. Finally, data were only collected for moderate or severe COPD exacerbations that resulted in an emergency department visit or hospitalization, so there may have been mild exacerbations treated in the outpatient setting that were not captured.
Despite these limitations, this study adds data to an area of COPD management that currently lacks strong clinical guidance. Since investigators had access to clinician notes, we were able to capture ICS tapers even if patients did not receive a prescription with specific taper instructions. The extended follow-up period of 12 months evaluated a longer potential time to impact of ICS discontinuation than is done in most COPD clinical trials.
Conclusions
Overall, very low rates of COPD exacerbations occurred following ICS discontinuation, regardless of whether a taper was used. The results suggest that there may be several appropriate ways to discontinue ICS therapy. However, there is insufficient evidence to support a particular taper or the need to taper at all. It seems to be safe to discontinue ICS therapy in patients who are unlikely to benefit from continued use; however, patient-specific factors should be considered as part of clinical decision making.