Retinoids vs. Combination Therapy with MOTS-C: Evidence-Based Recommendations
For most dermatological conditions requiring retinoid therapy, combination treatment with retinoids and other agents is more effective than retinoid monotherapy. This recommendation is particularly strong for conditions like palmoplantar pustulosis, where evidence shows significantly better outcomes with combination approaches.
Efficacy of Retinoids in Different Dermatological Conditions
- Retinoids are effective for various skin conditions including psoriasis, acne, and congenital ichthyoses, acting primarily as comedolytics with additional anti-inflammatory properties 1
- For mycosis fungoides and variants, retinoids can be used in combination with PUVA, IFNa, or TSEBT for patients with extensive infiltrated plaques and tumors or those refractory to skin-directed therapies 2
- In acne treatment, topical retinoids are recommended as monotherapy for primarily comedonal acne, but should be used in combination with topical or oral antimicrobials for mixed or inflammatory acne lesions 2
Evidence for Combination Therapy vs. Monotherapy
- For palmoplantar pustulosis, multiple randomized controlled trials show that the combination of oral PUVA with oral retinoids is significantly more effective than PUVA alone, with clearance rates of 61-100% for combination therapy versus 21-44% for PUVA monotherapy 2
- A Cochrane systematic review of interventions for palmoplantar pustulosis concluded that retinoids combined with PUVA have increased efficacy compared to PUVA used alone 2
- For psoriasis, retinoids combined with UVB phototherapy accelerate response and reduce the cumulative dosage of UVB and the dose of retinoid required to achieve clearance 2
Specific Combination Recommendations by Condition
Palmoplantar Pustulosis
- Unless contraindicated, the combination of oral PUVA with oral retinoids should be used as first-line treatment (strength of recommendation 1+; level of evidence A) 2
- Clearance rates with combination therapy (61-100%) significantly exceed those with PUVA monotherapy (21-44%) 2
Psoriasis
- For chronic plaque-like psoriasis, retinoids at 0.5 mg/kg/day combined with photo(chemo)therapy, tar, or dithranol is recommended 2
- Retinoids combined with UVB have been extensively studied and accelerate response to phototherapy while reducing cumulative UVB dosage 2
Acne
- Combination therapy using multiple topical agents that affect different aspects of acne pathogenesis is recommended for the majority of patients 2
- Topical retinoids should be used in combination with topical or oral antimicrobials in patients with mixed or primarily inflammatory acne lesions 2
Monitoring and Safety Considerations
When using retinoids (particularly acitretin), monitor:
Common side effects of retinoids include:
Special Considerations
- When adding retinoids to phototherapy, the light dose should be reduced by 30-50% to prevent excessive phototoxicity 2
- For hypohidrosis in congenital ichthyoses, oral retinoids may help improve thermoregulation 2
- Retinoids can interact with several medications including tetracyclines (increased risk of intracranial pressure), methotrexate (increased hepatotoxicity), and vitamin A supplements (hypervitaminosis A) 2, 4
Conclusion on MOTS-C Combination
While there is substantial evidence supporting the combination of retinoids with various therapies like PUVA, UVB, and antimicrobials, there is no specific evidence in the provided guidelines regarding combination with MOTS-C. Based on the available evidence, established combination therapies (particularly retinoids with phototherapy for conditions like palmoplantar pustulosis and psoriasis) should be preferred over unproven combinations.