Injection of collagenase clostridium histolyticum–aaes (CCH) for the treatment of moderate to severe cellulite in women’s buttocks demonstrated excellent durability of response at 6 months follow-up in an ongoing, 5-year, phase 3b, open-label extension study, Michael H. Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.
However, outcomes in that study, as well as in the earlier pivotal trials, were assessed via physician and patient subjective assessments of aesthetic appearance. In a separate presentation at the conference, Michael S. Kaminer, MD, presented a different study evaluating the objective quantifiable effects of CCH on buttock cellulite dimple volume using three-dimensional imaging. The results, indicating that smaller cellulite dimples responded better than larger dimples, he noted, were unexpected.
Discussant Zoe D. Draelos, MD, who practices in High Point, N.C., and is a consulting professor of dermatology at Duke University, Durham, N.C., put the two studies in perspective, explaining that there are multiple challenges associated with the use of CCH to treat buttock cellulite, and dermatologists need to understand them in order to maximize the benefit.
“There’s definitely a market for this therapy,” she observed, noting the plethora of over-the-counter products and devices sold for removal of cellulite. “I think if you manage patient expectations, this will be a very, very successful procedure.”
In 2020, the Food and Drug Administration approved subcutaneous injections of CCH (marketed under the brand name QWO) for treatment of cellulite in women’s buttocks on the basis of the randomized RELEASE-1 and -2 trials. But while this is a new indication for CCH, it is not a new drug. The medication has been approved for years for treatment of fibrotic band contracture disorders, namely Dupuytren’s contracture and Peyronie’s disease. The mechanism of action for treatment of cellulite involves a process dubbed enzymatic subcision, in which CCH breaks down mature collagen and stimulates new collagen formation and fat redistribution in an effort to achieve smoother skin contour.
“This adds a whole new wrinkle to injectables available in dermatology. We have fillers, we have toxins, and now we have enzymatic subcision,” Draelos commented.
Durability of Effects
Gold, founder of the Gold Skin Care Center and at the Tennessee Clinical Research Center, Nashville, reported on 483 women with moderate to severe buttock cellulitis who completed the 71-day, randomized, double-blind, phase 3 RELEASE-1 or RELEASE-2 studies and then enrolled in the open-label extension study. At the end of the randomized trial, 61.7% of women experienced at least a 1-level improvement on the Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), compared with 36.7% of placebo controls. The key finding in the interim analysis of the extension study: After the first 6 months, during which no one received any additional therapy, 52.7% of the CCH group still had at least a 1-level improvement in PR-PCSS, compared with the randomized trial baseline, as did 32.6% of controls.
Similarly, 63% of CCH-treated patients showed at least a 1-level improvement in the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) from baseline to the end of the randomized trial, and 52.7% met that standard after 6 months off treatment in the open-label extension. In contrast, the control group had response rates of 36.7% and 32.6%. There were no long-term safety concerns, according to Gold.
Measuring Cellulite Dimple Volume Shrinkage
Kaminer and coinvestigators measured the change in cellulite dimple volume from baseline to 30 days after the final injection of 33 buttock dimples in 27 women in order to get a quantifiable sense of the effectiveness of the CCH injection. To their surprise, smaller-volume dimples up to 118 mm3 showed a mean 43% reduction in volume, a significantly better result than the 15.8% reduction seen in dimples greater than 118 mm3.
“That’s almost counterintuitive, right? You’d think that larger dimples would have a bigger improvement, but it turns out that the smaller dimples do better,” he said at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.
Also, cellulite dimples in women age 40 and under responded significantly better than those in older women, added Kaminer, a dermatologist in private practice in Chestnut Hill, Mass., who is also on the faculty at Yale University, New Haven, Conn., and Brown University, Providence, R.I.
Challenges in Using CCH Therapy
Draelos, who is familiar with CCH, having worked on some earlier studies of the product, commented that “this is really the first medical treatment for cellulite that’s been proven to work.”
That being said, there are challenges with this therapy. While roughly 53% of women rated themselves as having at least a 1-level improvement after 6 months of follow-up, so did 33% of placebo-treated controls, for a placebo-subtracted 20% response.
“Is a 1-grade improvement going to be enough for women to engage in this procedure? You do need to remember that it takes multiple injections: most need at least three injections to see durable impact. And there’s discomfort during the procedure and afterwards during the healing process because the mechanism of action is enzymatic. You’re breaking down fibrous bands, and that’s a proinflammatory process. Many women who undergo this procedure may have discomfort and bruising, and they should be warned that this is not a procedure to do before taking a cruise or wearing a bikini. Also, it’s important to note that many women will have discomfort in the area where they sit, so if they have a job where they need to be sitting for long periods of time they need to plan their activities around this particular procedure,” the dermatologist said.
Another consideration: “The area they actually studied – the buttocks – is an area where I’m not sure a lot of women would expose their skin in public. I think thigh dimpling is more bothersome because it shows in shorts and other types of clothing. We need to figure out if the injections work on the posterior thighs, the most common place most postpubertal women get cellulite,” Draelos noted.
She wasn’t surprised that smaller cellulite dimples did better. Larger dimples presumably have a broader fibrous attachment and tighter fibrous band. She found the less robust outcomes in women over age 40 similarly unsurprising, since cellulitis seems to worsen with age. Cellulitis can’t really be called a disease, anyway, since it occurs in about 90% of postpubertal women.
One last tip about managing patient expectations: “Let a woman know that it’ll be better, but it won’t be gone,” she said.
Gold and Kaminer reported serving as paid investigators for and consultants to Endo Pharmaceuticals, the study sponsor and manufacturer of CCH, as well as for several other pharmaceutical companies.
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This article originally appeared on MDedge.com, part of the Medscape Professional Network.
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