Topical Tretinoin Photoaging RCTs: GRADE Evidence Review

How Strong Is the Evidence?

GRADE grades a body of evidence for one comparison and outcome, not for a drug as a whole, and this page does not assign a GRADE certainty rating. The evidence discussed here is a small trial set: five controlled trials described in the Renova 0.02% cream label [1] and one biopsy study that used 0.1% cream [2].

What the Renova Label Trials Showed

Four multicenter trials and one single-center randomized trial compared Renova 0.02% cream with vehicle on the face for 24 weeks alongside a comprehensive skin care and sun avoidance program: 324 evaluable patients on tretinoin and 332 on vehicle [1]. Two of the five adequately demonstrated efficacy for fine facial wrinkling; the trials did not adequately demonstrate efficacy for coarse wrinkling, mottled hyperpigmentation, tactile roughness or laxity [1]. The label also notes that many patients in the vehicle group achieved desired palliative effects on fine wrinkling with the skin care and sunlight avoidance program alone [1].

Among lightly pigmented subjects (279 tretinoin, 280 vehicle), moderate improvement in fine wrinkling, a fall of three or more units on a 10-unit scale, occurred in 10% versus 3%; mild improvement in 15% versus 9%; minimal improvement in 35% versus 27%; no change in 40% versus 58% [1]. A single-center study of 107 darkly pigmented, mostly African-American subjects found minimal or mild improvement in 43% of vehicle users versus 29% of Renova users; the label says this may reflect the small size of the study [1].

The Collagen Biopsy Evidence

In a separate comparison of biopsies from 26 healthy subjects, collagen I formation was 56% lower in photodamaged skin than in sun-protected skin (P<0.001) [2]. Griffiths and colleagues also treated 29 patients with photodamaged skin for 10 to 12 months: 15 with 0.1% tretinoin cream and 14 with vehicle [2]. Tretinoin produced an 80% increase in collagen I formation, against a 14% decrease with vehicle (P=0.006) [2]. That study used 0.1% cream, not the 0.02% the Renova label covers, and measured collagen rather than wrinkles; the label says no correlation was made between procollagen I propeptide staining after 0.1% cream and collagen I levels or observed clinical effects [1].

Irritation and Label Warnings

In the Renova label's vehicle-controlled studies of 339 patients, almost all reported local reactions such as peeling, dry skin, burning, stinging, erythema or itching; 32% had irritation that was severe, led to temporary discontinuation or led to use of a mild topical corticosteroid, and about 4% discontinued because of adverse reactions [1].

The label says safety and efficacy of daily use beyond 52 weeks have not been established, and that patients may lose some of the mitigating effects after 12 weeks without Renova [1]. The label says not to use Renova if the patient is pregnant or attempting to become pregnant, is sunburned, has eczema or other chronic skin conditions of the face, is inherently sensitive to sunlight, or is taking photosensitizing drugs such as thiazides, tetracyclines, fluoroquinolones, phenothiazines or sulfonamides [1].