I am always reading something conflicting about steroids. They are good for you and they are also bad for you. The latest controversy is the role of inhaled corticosteroids in Chronic Obstructive Pulmonary Disease. Unlike asthma, the use of inhaled corticosteroids (ICS) has never demonstrated their clinical benefits consistently. They have been shown to improve symptoms, lung function and quality of life as well as reducing exacerbation in patients with FEV1 of less than 60% predicted. However, inhaled corticosteroids have not been demonstrated to prevent the progression of the disease nor to improve survival.
Recently, the use of inhaled corticosteroids, particularly with fluticasone and especially in high doses, has been associated with an increased risk of pneumonia as demonstrated in TORCH and INSPIRE trials. Inhaled corticosteroids are also associated with side effects such as oral candidiasis and hoarse voice and skin bruising. As such, we are seriously re-evaluating the role of inhaled corticosteroids in COPD and to identify candidates who will truly benefit from such therapy.
In fact, the approach to managing COPD has been updated recently. According to the GOLD (Global Initiatives for Chronic Obstructive Disease) guidelines for COPD, inhaled corticosteroid is now listed as third line treatment option whereas LAMA (long acting muscarinic antagonist) and LABA (long acting beta agonist) are the mainstay of COPD therapies. As such, we are also seeing the explosion of new inhalation devices either as single agent of LAMA or LABA or a combination of these two medications.
In my practice setting, I see many COPD patients who are currently on a combination therapy with fluticasone and salmeterol (in addition to tiotropium). The missing piece with the new guideline is how we should go about managing patients who are currently on high doses of fluticasone (1000mcg/day). Given the demonstrated increased risk of pneumonia, how do we go about adjusting their treatment taking into considerations of their recent history of COPD exacerbation, pnuemonia, and other factors such as frailty and comorbidities?
- Do we reduce the dose of fluticasone? If so, what’s the lowest effective dose to prevent exacerbation?
- Do we get rid of fluticasone? If so, how? Abruptly or gradually over several months?
- Do we switch over to budesonide which is known to be less potent than fluticasone?
- Do we add a long acting beta agonist or long acting muscarinic antagonist (if not already on these therapies) to help optimize the management of COPD?
The WISDOM study evaluated if inhaled cortiocsteroids can be safely withdrawn. The study compared stable COPD patients who were on triple therapy with ICS, LABA and LAMA to the same patient population whose ICSs were gradually withdrawn over a 3-month period. The results indicate there was a non-statistically significant increase in COPD exacerbation in the ICS withdrawal group that was transient and did not sustain over the study period (HR 1.06, p=0.35). There was also a significant greater reduction in lung function (reduction in FEV1) in the ICS withdrawal group, which I thought was somewhat alarming. However, the authors pointed out that these results were not related to any changes in exacerbation. In any case, the WISDOM study has confirmed that it is probably safe to withdraw ICS without any significant harmful effects in an otherwise stable COPD patient.
Kaplan has proposed an algorithm for stepping down inhaled corticosteroids in patients with COPD. He points out that there is a subgroup of COPD patients who may benefit from continued inhaled corticosteroid therapy; these include patients with certain COPD phenotypes (patients with ACOS – asthma chronic obstructive syndrome, frequent exacerbators and those with eosinophilia). For individuals who do not meet these criteria, it may be prudent to assess for stepping down therapy, especially the elderly with several co-morbidities. He has also included a detailed algorithm which has become my new best friend when I conduct med review for my COPD patients.
It is an exciting time in COPD – we have many treatment options available now in different inhalation devices catered to different needs (e.g. cognitive impairment, frailty, convenience) but I wish there is a better emphasis in how we deal with patients who are currently on an inhaled cortiocsteroids to determine whether any adjustment is needed. It seems, to me at least, withdrawing the ICS should be one of the next depresribing initiatives.