Clinical Evidence Concern Over New COPD Update

There has been some criticism of the recent update to COPD management guidelines published by GOLD, with concern over the how much of the changes are based on clinical evidence.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recently published its first update in five years on treatment recommendations for COPD. It now favors fixed-dose LABA/LAMA combinations over ICS/LABA combinations. It had previously recommended the use of either a LABA/LAMA or ICS/LABA in the majority of COPD patients. (Also see "GOLD Pushes LABA/LAMA Class In New COPD Treatment Update" - Scrip, 28 Nov, 2016.)

However, not everyone is convinced of the changes.

Chiesi Farmaceutici SPA, while acknowledging an update was "a positive step forward", has some concerns.

"The evidence base of the new version of the GOLD report is limited in certain key areas, since, as clearly written in the body text, the basis for treatment recommendations is only partially from evidence coming from randomized clinical trials," said Professor Stefano Petruzzelli, chief medical officer and head of global clinical development for Chiesi.

Chiesi does not market a combined LABA/LAMA product. In addition, in September this year, the Italian firm was the first to file a triple combination product in Europe, the ICS/LAMA/LABA product CHF 5993.

It is likely that the publication of data from Novartis AG's FLAME study comparing its Ultibro Breezhaler (a LABA/LAMA) with GlaxoSmithKline PLC's Advair/Seretide (an ICS/LABA) in reducing COPD exacerbations was a significant catalyst in changing the guidelines. (Also see "Novartis's FLAME Rockets LAMA/LABAs Into COPD Limelight At GSK's Expense" - Scrip, 26 May, 2016.)

Chiesi however notes that "this effect was not demonstrated in patients with a history of more than one exacerbation" and so the recommendation to step up from LAMA to LABA/LAMA "is at least questionable and not supported by evidence." Even more important, according to Chiesi, the new guidelines are not in line with the approved indications of all LABA/LAMA currently available to healthcare professionals. The approved indications for these products are essentially restricted to relieve symptoms, and do not include the use in patients with history of exacerbations, said Chiesi. "In short, the GOLD report therefore appears to be recommending off label and unapproved clinical use of these products in patients at high risk of exacerbations."

Chiesi is also concerned about the "repeated" references in the GOLD text to the risk of pneumonia with the use of inhaled corticosteroids (ICS). "A clear reference to the positive risk-benefit ratio with use of ICS in COPD (i.e. the marked reduction of exacerbations being significantly greater than the increase of pneumonia), as recently established by the European Pharmacovigilance Risk Assessment Committee (PRAC) and endorsed by the CHMP and European Commission, would have represented a more balanced vision to support the treatment recommendations. Moreover, there is no mention to the fact that this increase risk does not translate into a greater risk of death."

Professor Petruzzelli concluded: "We consider that the new GOLD report is not fulfilling the goal of clarifying the therapeutic approach to COPD patients compared with previous recommendations based on a convincing level of evidence."

Novasecta analysts Brian McGee told Scrip that GOLD guidelines have evolved substantially in the last decade "to recognize the need for a more holistic approach to the management of COPD and part of that evolution is an increasing willingness to look beyond clinical trial data to clinical experience, opinion and extrapolation – the so called ‘grey hair factor’ – and it seems there is an ideological preference for LAMA/LABAs."

According to McGee, "While it is too simplistic to think of winners and losers in a guideline, these guidelines are often translated into simplified marketing messages by the key players. Given that GlaxoSmithKline PLC, Novartis and Boehringer Ingelheim GMBH all have LABA/LAMAs it looks like they will all jointly ride the wave of LABA/LAMA support rather than fighting the tide."