How to Optimize Rosacea Treatment for Better Patient Outcomes: An Opinion Piece

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J Clin Aesthet Dermatol. 2022;15(7):E60–E62.

by Martin Schaller, MD, PhD; Jerry Tan, MD, FRCPC; and Guy Webster, MD, PhD, FAAD

Dr. Schaller is with the Department of Dermatology at Eberhard Karls University Tuebingen in Tuebingen, Baden-Wuerttemberg, Germany. Dr. Tan is with the Windsor Clinical Research Inc and the Department of Medicine at University of Western Ontario in Windsor, Ontario, Canada. Dr. Webster is with the Department of Dermatology at Thomas Jefferson University in Philadelphia, Pennsylvania. 

FUNDING: This article was funded by Galderma SA, Switzerland.

DISCLOSURES: Dr. Schaller reports grants and consultancy fees from Galderma, consultancy fees from Abbvie, consultancy fees from Bayer Healthcare, consultancy fees from Infectopharm, consultancy fees from Lilly, outside the submitted work. Dr. Tan reports consultancy fees from Bausch, consultancy fees from Leo, consultancy fees from L’Oréal, consultancy fees from Galderma, consultancy fees from Promius, consultancy fees from Sun, outside the submitted work. Dr. Webster reports consultancy fees from Almirall, consultancy fees from Galderma, consultancy fees from Nflection, consultancy fees from Ortho, outside the submitted work.

ABSTRACT: Rosacea is a chronic disease requiring long-term management. However, it is often treated according to package label instructions, which reflect the conditions of a Phase III study rather than a chronic disease. Furthermore, due to a lack of clinical data or guidelines on long-term treatment, many clinicians choose to discontinue treatment once success has been reached, rather than continuing with maintenance therapy. As experienced practicing dermatologists and investigators in the field, in this article we address the current evidence gaps in rosacea management and provide practical advice to clinicians on how optimal outcomes can be achieved and maintained in patients with rosacea in real-world practice, based on our own experience and the available clinical data.

Keywords: Rosacea, treatment, management, chronic, best practice, optimal, outcomes, maintenance


Room for improvement: what are the current pitfalls in rosacea management?

Clinical studies have shown that achieving complete clearance in rosacea is possible; however, multiple factors can prevent optimal outcomes from being reached.1,2 Firstly, current data suggests that few available treatments can realistically achieve complete clearance in the majority of patients.1–3 Even among those treatments that do make this goal possible, many are only indicated to treat a single feature of rosacea, so may need to be used in combination for patients presenting with multiple signs and symptoms.4–6 Furthermore, although systemic monotherapy can be an effective option for achieving and maintaining complete clearance, systemic treatments are often only prescribed as part of combination therapy in case of incomplete response to initial topical treatments.7,8 There is therefore a lack of clarity among clinicians regarding when and how to use different treatment modalities and combinations in order to achieve optimal outcomes in different patients.1,2,9,10 Additionally, both the impact of rosacea symptoms and the benefits of reaching complete clearance, such as patients being rosacea-free for longer and having a better overall quality of life, are often overlooked by clinicians.3,9,11 Due to these factors, we believe that many patients with the potential to attain complete clearance might be under-treated, as was suggested in a recent survey of 300 patients with rosacea, in which only one percent of respondents rated themselves as “clear” (Investigator Global Assessment [IGA] of 0) when reflecting over the previous year.11

Although rosacea is a chronic disease characterized by periods of remissions and flare-ups that requires lifelong management, it is often treated acutely in line with the 12- to 16-week duration of most clinical studies, approved usage and prescribing guidance.1–5,12–14 This highlights a data gap caused by a lack of real-world evidence on the effect of continued treatment beyond 12 to 16 weeks, leading to an inadequate understanding among clinicians of how long the different treatment modalities and combinations can be used.1,9,10,15 Moreover, maintenance therapy after reaching treatment success, often defined as almost or complete clearance in clinical studies, might be expected to extend time to relapse, yet we are frequently asked in practice and at congresses about strategies to maintain control once treatment success has been achieved.3,16 This reflects a paucity of evidence on maintenance therapy, which has resulted in a lack of clarity among clinicians on how to use the different treatment modalities and combinations to maintain treatment success, as well as duration of maintenance therapy use.2,10,15,16

What is driving the current gaps in rosacea management?

The Rosacea Consensus (ROSCO) panel recommend aiming for complete clearance (IGA 0) in rosacea management, however regulatory authorities and treatment guidelines generally evaluate treatment success as “clear” (IGA 0) or “almost clear” (IGA 1) in clinical studies.3,9,10 As a result, patients who reach treatment success within study time frames might not necessarily reach complete clearance, meaning data-driven insights are lacking on how to achieve clearance and how long it can take to do so.3 Additionally, IGA treatment success does not imply symptom clearance; therefore, this regulatory measure might inadequately capture holistic success in rosacea treatment.3 Furthermore, despite the existence of long-term data for certain treatments, prescribing guidance commonly recommends short treatment lengths of 12 to 16 weeks based on the duration of pivotal trials, which might not allow enough time for patients to reach the full potential of their treatment.1,2,4,5,13–15,17–19

Moreover, the standard pivotal trial endpoints required by regulatory authorities and cited in treatment guidelines do not cover the entire patient experience, as generally only inflammatory lesions and erythema of rosacea are assessed.3,10 In contrast, expert groups including the American Acne and Rosacea Society and the ROSCO panel promote a phenotypic approach to rosacea diagnosis and management, based on consideration of all presenting disease features.9,10 Even after achieving visible clearance, patients might still be sub-optimally managed if they continue to experience rosacea symptoms such as stinging, burning, pain or itching, which can have a large impact on quality of life.9,11 Thus, we believe that rosacea management could be improved in the future by the development of a more comprehensive measure of treatment success, designed for use in clinical practice, that takes into account all signs and symptoms, as well as patient satisfaction. 

Maximizing results: how can optimal outcomes be achieved?

Clinical studies and prescribing guidance do not reflect the variety of situations clinicians face in real-world practice; therefore, treatment decisions should also be informed by clinical expertise and patient factors in order to reach optimal outcomes.9 Due to the individual nature of each patient’s disease presentation and circumstances, clinicians should also consider additional factors, such as patient preferences for treatment modality or dosing regimen, comorbidities, budget, concern about adverse events, and prior therapies.9,20–22 We believe that aligning treatment with patients’ needs in this way can improve adherence, treatment outcomes, and patient satisfaction.

Furthermore, clinical studies often measure treatment success based on visible signs only, but in real-world practice, success should be measured based on the factors that are important to patients.3,16 Accordingly, we recommend that clinicians should also consider symptoms when deciding on a treatment plan and continue to monitor these, as there might be a need to incorporate mitigation of both signs and symptoms of rosacea in order to successfully reduce the disease burden and achieve the patient’s idea of treatment success.11

We recommend introducing systemic treatments earlier, rather than with a stepwise approach, as this can reduce time to treatment success.1 We also recommend that clinicians not only consider systemic treatment for patients with an inadequate response or intolerance to topicals, but likewise for those with severe disease or a high burden.16 While systemic monotherapy could be considered in these cases, combination treatment can also be an effective solution for patients with multiple features, severe disease, a high burden, or those who need results quickly.9,16 Particularly with systemic treatments, safety and tolerability should be taken into consideration when prescribing courses beyond 30 days.

Treatment adherence is key to successful rosacea management, and we believe that this can be encouraged via informed decision making, choosing treatment modalities and dosing regimens that are simple and easy to assimilate into daily life.23 Additionally, clinicians can help manage expectations by discussing treatment aims and likely duration with the patient, making sure to clarify that not all patients are able to reach complete clearance in the same time frame or in the usual 12- to 16-week prescription duration, and that treatment adjustments might be needed.9,15,17 We have found that adherence can also be improved by scheduling regular follow-up visits, including via telemedicine, and reiterating the goals of therapy. Furthermore, clinicians should educate patients on the nature of rosacea as a chronic disease that requires long-term treatment, as well as the importance of a good skincare routine and trigger avoidance.9

How long does it really take to reach optimal outcomes?

Achieving treatment success in rosacea takes time, so rather than relying on the minimum treatment duration required for drug approval, the target should be to treat until the patient is satisfied.16 This is especially true given that long-term efficacy and safety data does exist for some rosacea treatments.15,17–19 Long-term data up to 52 weeks is available for metronidazole 0.75% cream (26 weeks), azelaic acid 15% gel (40 weeks), ivermectin 1% cream (52 weeks), oxymetazoline 1% cream (52 weeks), brimonidine tartrate gel 0.5% (52 weeks), as well as doxycycline 40mg modified-release capsules (52 weeks), meaning clinicians can be more confident in prescribing these for longer periods of time.15,17–19,24 Importantly, the time taken to reach optimal outcomes can depend on several patient factors, warranting an individualized treatment approach with durations tailored to each patient’s needs.

How can optimal outcomes be maintained?

Once treatment success has been reached, we recommend that clinicians actively aim to prolong remission and prevent relapse for as long as possible. It has been shown that treatment up to 52 weeks can reduce the rate of relapse and increase the proportion of patients achieving almost or complete clearance, and continuous treatment such as this might be required to maintain results in some patients.15,17,18 Conversely, given the unique characteristics of rosacea features in each individual, other patients can remain in remission while taking breaks from treatment.9 Once optimal outcomes have been reached, we recommend that treatment should be tapered by slowly reducing the dosage, allowing for the dosage to be increased again if signs or symptoms worsen.16 This can be reassuring for patients worried about relapse once they stop treatment. In the case of combination therapy, we recommend that clinicians taper treatments one by one, choosing which treatment to taper based on phenotype presentation, clinical expertise, patient preference, cost, and potential for adverse events.

Conclusion

Recent advances in our understanding of rosacea treatment have highlighted the patient benefits of reaching and maintaining complete clearance.3,9 However, there is inadequate data-driven guidance available on how to use the different treatment modalities and combinations to achieve this goal.1,2,9,10,15 Although clinical studies provide evidence-based insights, they can be of limited value in real-world practice due to their short durations and narrow endpoints that do not reflect the entire patient experience.1–3,15 Therefore, insights from experienced practicing dermatologists and investigators in the field may help bridge knowledge gaps by providing guidance on how to attain optimal rosacea outcomes via long-term management and consideration of individual patient needs.

Acknowledgements

Manuscript preparation and editorial assistance was provided to the authors by Abira Sittampalam and Paige Yates of Havas Life Medicom, UK, and was funded by Galderma SA, Switzerland. This paper was funded by Galderma SA, Switzerland.

References

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  2. Taieb A, Ortonne JP, Ruzicka T, et al. Superiority of ivermectin 1% cream over metronidazole 0.75% cream in treating inflammatory lesions of rosacea: a randomized, investigator-blinded trial. Br J Dermatol. 2015;172(4):1103­–1110.
  3. Webster G, Schaller M, Tan J, et al. Defining treatment success in rosacea as ‘clear’ may provide multiple patient benefits: results of a pooled analysis. J Dermatolog Treat. 2017;28(5):469–474.
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  8. van Zuuren EJ, van der Linden MMD and Arents BWM. Rosacea treatment guideline for the Netherlands. Br J Dermatol. 2020;182(6): 1504–1506.
  9. Schaller M, Almeida LMC, Bewley A, et al. Recommendations for rosacea diagnosis, classification and management: update from the Global ROSacea COnsensus 2019 Panel. Br J Dermatol. 2020;182(5):1269–1276. 
  10. Del Rosso JQ, Tanghetti E, Webster G, et al. Update on the management of rosacea from the American Acne & Rosacea Society (AARS). J Clin Aesthet Dermatol. 2019;12(6):17–24.
  11. Steinhoff M, Harper J, Gieler U, et al. The BMJ Hosted Content 2020. Beyond the visible: rosacea and psoriasis of the face. Available at: https://hosted.bmj.com/rosaceabeyondthevisible. Date accessed: September 2021.
  12. Salzer S, Ruzicka T and Schauber J. Face-to-face with anti-inflammatory therapy for rosacea. Exp Dermatol. 2014;23(6):379–381.
  13. Stein Gold L, Kircik L, Fowler J, et al. Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies. J Drugs Dermatol. 2014;13(3):316–323.
  14. ROZEX® (metronidazole) 0.75% w/w Cream. Summary of Product Characteristics. April 2021.
  15. Stein Gold L, Kircik L, Fowler J, et al. Long-term safety of ivermectin 1% cream vs azelaic acid 15% gel in treating inflammatory lesions of rosacea: results of two 40-week controlled, investigator-blinded trials. J Drugs Dermatol. 2014;13(11):1380–1386.
  16. Asai Y, Tan J, Baibergenova A, et al. Canadian clinical practice guidelines for rosacea. J Cutan Med Surg. 2016;20(5):432–445.
  17. Draelos ZD, Gold MH, Weiss RA, et al. Efficacy and safety of oxymetazoline cream 1.0% for treatment of persistent facial erythema associated with rosacea: Findings from the 52-week open label REVEAL trial. J Am Acad Dermatol. 2018;78(6):1156–1163.
  18. Dahl MV, Katz HI, Krueger GG, et al. Topical metronidazole maintains remissions of rosacea. Arch Dermatol. 1998;134(6):679–683.
  19. Moore A, Kempers S, Murakawa G, et al. Long-term safety and efficacy of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of a 1-year open-label study. J Drugs Dermatol. 2014;13(1): 56–61.
  20. Hofmann MA and Lehmann P. Physical modalities for the treatment of rosacea. J Dtsch Dermatol Ges. 2016;14 Suppl 6:38–43.
  21. Buddenkotte J and Steinhoff M. Recent advances in understanding and managing rosacea. F1000Res. 2018;7:1885. 
  22. Schaller M and Gonser L. A tailored approach to the treatment of a patient with a severe dynamic manifestation of rosacea: a case report. Drugs R D. 2016;16(3):279–283.
  23. Kuo S, Huang KE, Davis SA, and Feldman SR. The rosacea patient journey: a novel approach to conceptualizing patient experiences. Cutis. 2015;95(1):37–43.
  24. Del Rosso JQ, Brantman S, Baldwin H. Long-term inflammatory rosacea management with subantibiotic dose oral doxycycline 40 mg modified-release capsules once daily. Dermatol Ther. 2022;35:e15180. 

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