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Combination therapy yields greater improvement in severe rosacea

James Q. Del Rosso

Patients with rosacea treated with topical ivermectin 1% cream and oral doxycycline modified-release 40 mg capsules had greater visible improvement and decreased stinging and flushing compared with monotherapy, according to data from a multicenter, randomized, parallel-group comparison study conducted by James Q. Del Rosso, DO, of JDR Dermatology Research/Thomas Dermatology in Las Vegas, and colleagues.

In the 12-week comparative study, 273 adults with severe rosacea were randomized to either topical ivermectin 1% cream (IVM) and oral doxycycline modified-release 40 mg (n = 135) or monotherapy treatment of IVM and placebo (n = 138).

The primary endpoint was the percentage change in inflammatory lesion count from baseline to week 12.

Both treatment groups experienced a reduction in inflammatory lesions from baseline, but the decrease was significantly greater in the combination therapy group starting from week 4 (P = .007), according to the study.

At week 12, the mean percentage reduction in inflammatory lesions was -80.3 in the combination arm vs. -73.6 in the monotherapy arm (P = .032).

Additionally, more patients achieved 100% lesion clearance at week 12 with combination therapy compared with monotherapy (17.8% vs. 7.2%; P = .006).

In an interview with Healio Dermatology, Del Rosso discussed the phase 3b/4 results and how their findings will affect the treatment of rosacea.

Healio: What do dermatologists need to know about your results in this phase 3b/4?

Del Rosso: This study demonstrates that in adult patients presenting with severe rosacea with papulopustular lesions, topical ivermectin 1% cream (Soolantra, Galderma) applied once daily and oral doxycycline modified-release 40 mg capsule once daily (Oracea, Galderma) are both highly effective as monotherapy.

However, the combination of these agents in this severe population has been shown to provide a greater reduction in papulopustular lesions, observed as early as 4 weeks, and throughout the 12-week duration of the study.

Importantly, the combination regimen was able to increase the percentage of patients who achieved complete clearance of rosacea by the end of the study, a goal that is desired by both the patient and their dermatologist. It is important to point out that proper skin care, with a gentle cleanser, moisturizer and sunscreen, is an integral component of rosacea management.

What I also take home from this study is that there is benefit in some patients, especially those with severe disease, to combine agents that have activity against papulopustular lesions, as there appears to be an incremental improvement that is very clinically relevant in some patients.

Healio: Was there anything along the way that surprised you within this study?

Del Rosso: Not really. We already knew from the phase 3 randomized controlled trials completed in adults with rosacea that Soolantra cream applied once daily markedly reduces papulopustular lesions. In fact, the average baseline number of papulopustular lesions in the trials was approximately 30, which is a fairly high average lesion count in rosacea.

In fact, I expected that adding another agent known to be effective in reducing papulopustular lesions of rosacea, namely Oracea capsules, would increase the magnitude of response such that some patients will experience a noticeable augmented benefit, which in some cases would clear facial skin of the visible signs of that disease that were evaluated over the 12-week duration of the study.

Both agents have been shown to be well-tolerated and safe, which proved to be the case during this study also.

Healio: What are some of the current challenges in treating rosacea?

Del Rosso: Rosacea is a chronic disease that flares and remits, often in an unpredictable pattern. Some triggers can be avoided, but it is hard to fully control all of the environmental or personal factors that can sometimes exacerbate rosacea.

Compliance with treatment is the biggest challenge, as even if patients use treatment and improve, they often stop treatment, hoping their rosacea will not return.

Guess what? It usually does.

An advantage of using doxycycline modified-release 40 mg capsule once daily is that it is subantibiotic, meaning it does not promote antibiotic resistance via selection pressure. This is especially important with a chronic disease such as rosacea.

Healio: Are there additional plans to further explore this research?

Del Rosso: I am not sure what is specifically being planned right now. However, this study opens the door for additional research on combination therapies for rosacea. Rosacea has many clinical features that may or may not manifest in a given patient.

Therefore, rosacea therapy must be customized to the individual patient's needs.

Healio: Can these study results affect the clinical practice of rosacea now or in the future?

Del Rosso: Absolutely. Clinicians can now ask themselves which therapeutic approach, including the selection of therapeutic agents chosen, is most likely to achieve the optimal clearance of rosacea signs and symptoms in each patient as effectively and expeditiously as possible.

Disclosures: Del Rosso reports he is a researcher for BiopharmX, Botanix, Dermira, Foamix, Galderma, Leo Pharma (Bayer Dermatology), Novan, Ortho Dermatology, Sol-Gel and Sun Pharma. He is a speaker for Almirall, Dermira, Galderma, Leo Pharma (Bayer Dermatology), Mayne Pharma and Ortho Dermatology. Del Rosso also consults for Almirall, BiopharmX, Cassiopeia, Foamix, Hovione, Leo Pharma (Bayer Dermatology), Mayne Pharma, Novan, Ortho Dermatology and Sol-Gel, and he is a Galderma advisory board member. Please see the study for all other authors’ relevant financial disclosures.