Rare diseases refer to a collective term for diseases with extremely low prevalence and incidence rates. Due to the lack of approved drugs for most rare diseases, off-label drug use has become an important clinical treatment option. To standardize the management of off-label drug use for rare diseases in China, the Rare Diseases Branch of Beijing Medical Association, the Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association, the Clinical Pharmacology Professional Committee of the Chinese Pharmacological Society, the National Joint Meeting of Rare Disease Academic Organizations, and the School of Public Health, Peking University jointly initiated the development of this expert consensus on off-label drug use for rare diseases (2026 edition). A systematic retrieval was conducted on guidelines, clinical recommendations, expert consensuses, and other relevant documents related to the 207 rare diseases included in the two batches of the national rare disease catalogue. A total of 1,870 articles were included after two rounds of screening and expert verification, and 5,497 disease-drug combinations were extracted. Through verification against the National Medical Products Administration official website and Chinese drug package inserts, 4,559 disease-drug combinations were identified as off-label use through verification, covering 157 rare diseases and 1,050 drugs. Randomized controlled trials and systematic reviews/Meta-analysis were searched, and the adapted Thomson evidence grading system for evidence rating were adopted. After multiple rounds of review by the same-specialty, cross-specialty, and external review groups, each disease-drug combination beyond the instructions is recommended by all experts and considered as the final consensus. Finally, 770 off-label disease-drug combinations were recommended, covering 121 rare diseases in the two batches of the national rare disease catalogue. Among them, 91 (11.82%), 51 (6.62%), 53 (6.88%), and 575 (74.68%) disease-drug/drug category combinations were supported by Grade A, B1, B2, and C evidence, respectively. This consensus can provide an important evidence-based basis for rare disease clinical practice, drug regulation, and medical insurance policy formulation.

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