From the Guidelines
Imidazoquinolines, specifically imiquimod 5% cream, are the most effective treatment for actinic keratosis, with a complete clearance rate of 50% and a low risk of side effects, as demonstrated in a meta-analysis of five RCTs 1.
Key Points
- Imiquimod 5% cream is a topical immune-response modifier that stimulates the innate immune system to target abnormal tissue.
- The most recent and highest quality study, a meta-analysis of five RCTs, showed a 50% complete clearance rate for imiquimod 5% cream in the treatment of actinic keratosis 1.
- Imiquimod 5% cream is applied at night and washed off in the morning, 8 hours later, three times a week for 4 weeks, which can be repeated for a further 4 weeks if needed.
- Common side effects include local skin reactions such as redness, swelling, erosion, and scabbing, which are actually indicators of therapeutic inflammatory response.
- Systemic absorption is minimal, making imiquimod 5% cream relatively safe for topical use.
Treatment Options
- Imiquimod 5% cream is the most effective treatment for actinic keratosis, with a complete clearance rate of 50% 1.
- Other treatment options, such as 5-FU 0.5% in 10% salicylic acid, have lower complete clearance rates, ranging from 32% to 55% 1.
- Diclofenac 3% gel has a complete clearance rate of 20% 1.
Patient Counseling
- Patients should be counseled carefully to anticipate potential side effects and to understand the importance of completing the full treatment course.
- About 50% of patients discontinue treatment at 6 weeks due to disappearance of the AK 1.
From the FDA Drug Label
Adverse events which occurred more frequently in imiquimod-treated subjects compared with vehicle-treated subjects generally resembled those seen in studies in indications approved for adults and also included otitis media (5% imiquimod vs. 3% vehicle) and conjunctivitis (3% imiquimod vs. 2% vehicle). Systemic absorption of imiquimod across the affected skin of 22 subjects aged 2 to 12 years with extensive MC involving at least 10% of the total body surface area was observed after single and multiple doses at a dosing frequency of 3 applications per week for 4 weeks The overall median peak serum drug concentrations at the end of week 4 was between 0.26 and 1.06 ng/mL except in a 2-year old female who was administered 2 packets of study drug per dose, had a Cmax of 9. 66 ng/mL after multiple dosing. Children aged 2-5 years received doses of 12.5 mg (one packet) or 25 mg (two packets) of imiquimod and had median multiple-dose peak serum drug levels of approximately 0.2 or 0.5 ng/mL, respectively. Children aged 6-12 years received doses of 12.5 mg, 25 mg, or 37.5 mg (three packets) and had median multiple dose serum drug levels of approximately 0.1,0.15, or 0. 3 ng/mL, respectively.
The imidazoquinoline mentioned in the question refers to imiquimod, an immune response modifier.
- Systemic absorption of imiquimod was observed across the affected skin of subjects.
- Median peak serum drug concentrations varied based on the dose and age of the subjects.
- The mechanism of action of imiquimod cream in treating AK lesions is unknown 2.
From the Research
Imidazoquinoline Overview
- Imidazoquinolines are a class of immune response modifiers, with imiquimod being the first approved member for the topical treatment of external genital and perianal warts 3.
- Imiquimod is a synthetic imidazoquinoline amine that enhances both innate and acquired immune pathways, resulting in antiviral, antitumour, and immunoregulatory activities 3, 4.
Mechanism of Action
- The mechanism of action of imiquimod involves cytokine induction in the skin, triggering the host's immune system to recognize and eradicate viral infections or tumors 3, 5.
- Imiquimod acts as a toll-like receptor-7 agonist, exerting its anti-tumor effect via modification of the immune response and stimulation of apoptosis in cancer cells 6.
Clinical Applications
- Imiquimod 5% cream is approved for the treatment of superficial basal cell carcinoma, external genital warts, and actinic keratosis 4, 6, 5.
- Imiquimod has shown promise in the treatment of other cutaneous and mucosal viral infections, dysplasias, and neoplasia, as well as potential vaccine adjuvants 3.
- Topical imiquimod therapy has been shown to polarize lymphoid and monocyte/macrophage populations to a Th1 and M1 cytokine pattern, effective in defense against tumors and viral infections 7.