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Published on: August 25, 2017

Is Kaposi's sarcoma the end of the OX40/OX40L axis in atopic dermatitis?

Shahram Salek-Ardakani1

  • 1YZ Consulting, La Jolla, CA, United States.

Frontiers in Immunology
|June 18, 2026
PubMed

Insights

The OX40/OX40L axis shows promise for atopic dermatitis but faces challenges. Kaposi

Area of Science:

  • Immunology
  • Dermatology
  • Pharmacology

Background:

  • The OX40/OX40L axis has a strong biological rationale for atopic dermatitis treatment.
  • Early clinical trials showed durable activity, but efficacy compared to other therapies is questioned.

Purpose of the Study:

  • To evaluate the therapeutic strategy for targeting the OX40/OX40L axis in atopic dermatitis.
  • To address concerns regarding safety, specifically Kaposi's sarcoma, in the context of OX40/OX40L modulation.

Main Methods:

  • Review of clinical development programs for OX40/OX40L inhibitors (rocatinlimab, amlitelimab).
  • Analysis of safety data, including cases of Kaposi's sarcoma.
  • Evaluation of biological plausibility and mechanistic understanding of the OX40/OX40L axis in relation to adverse events.

Main Results:

  • Discontinuation of rocatinlimab due to Kaposi's sarcoma cases.
  • Two cumulative cases of Kaposi's sarcoma reported in the amlitelimab program, some in patients with risk factors.
  • A causal link between OX40/OX40L modulation and Kaposi's sarcoma is unproven but biologically plausible.

Conclusions:

  • Kaposi's sarcoma cases highlight the limits of first-generation OX40/OX40L targeting strategies.
  • Future development requires a more selective approach focusing on molecule design, patient selection, and risk mitigation.
  • The OX40/OX40L axis may still hold therapeutic potential in atopic dermatitis with refined strategies.
Keywords:
HHV-8Kaposi’s sarcomaOX40 (TNFRSF4)OX40L (TNFSF4)antiviral immunityatopic dermatitisdrug safetyinflammation

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