Editor's Note: With the increasing aging population in China, major chronic diseases have become the leading cause of death and the most significant disease burden for Chinese residents. As an essential means of treating chronic diseases, medications urgently require scientific, rational, and precise usage and management. At a domestic academic conference, Professor Houwen Lin from Shanghai Jiao Tong University School of Medicine, gave a remarkable academic report titled "The Role of Clinical Pharmacy in the Diagnosis and Treatment of Major Chronic Diseases." He provided a detailed introduction of how the clinical pharmacy team at Renji Hospital, driven by clinical needs, established key technologies for precise medication and new drug clinical positioning for major chronic diseases such as cardiovascular metabolism, rheumatology, and oncology. This article summarizes the report's content for the readers of Hepatology Digest.Introduction
Under the dual influence of an aging population and lifestyle changes, China faces a complex and severe situation in chronic disease prevention and treatment. Statistics show that there are over 260 million chronic disease patients, including 170 million patients with multiple chronic diseases. To meet the urgent needs of drug therapy for chronic diseases, Renji Hospital has formed a multidisciplinary team led by clinical pharmacy, focusing on key scientific issues such as “selecting good drugs, using good drugs, and producing good drugs.” Supported by three national key research and development programs, major scientific and technological projects, and key overseas cooperation projects of the National Natural Science Foundation, the team has engaged in 16 years of dedicated research and clinical practice. They have concentrated on three main areas: “evidence-based medication decision-making for chronic diseases,” “individualized precise medication technology for chronic diseases,” and “clinical value-oriented drug development paradigms,” forming three innovative systems: “rational medication system,” “precise medication system,” and “new drug clinical positioning technology system.”
Establishing an Innovative Rational Medication System Through Scientific Evidence, Real-World Evidence, and Standardized Use
The team has developed key evidence-based technologies such as multi-source data fusion analysis, statistical framework interactive verification, rare event hierarchical analysis, decision tree-M nesting, and discrete event dynamic simulation. These technologies created evidence chains for cardiovascular, oncology, and rheumatology medications, with 22 evidence-based results cited in international guidelines, solidifying “scientific evidence.” For example, in studying adverse reactions to immune checkpoint inhibitors (ICI), the team thoroughly explored the characteristics of immune-related hepatitis (IRH). They found that the incidence of IRH ranges from 2% to 10%, with higher rates in combination therapy than in monotherapy, and a mortality risk as high as 31%. Early onset is insidious, making timely detection and early intervention crucial. This result provides important evidence for ICI treatment decisions and adverse reaction management.
Based on scientific evidence, the team focused on complex chronic diseases and established real-world cohorts for cardiovascular metabolism, rheumatology, and oncology. They proposed 52 innovative medication strategies and developed 17 medication guidelines. In the field of rheumatology drug therapy, the team was the first globally to propose a Chinese scheme for tofacitinib in treating polymyalgia rheumatica and a step-down scheme for biological agents in the Chinese population, establishing “real-world evidence.” They developed a rational medication decision system for chronic disease patients, which has been promoted to 108 medical institutions in 12 provinces and cities nationwide, benefiting 350,000 chronic disease patients and significantly improving the rational use of medications, achieving “standardized use.”
Establishing a Precise Medication System Through Genetic Testing, Fine-Tuned Typing, and Targeted Intervention
The team established an automated genetic testing platform integrating “tube laboratories,” “box laboratories,” and “microfluidic chips,” enabling rapid (15 minutes), highly sensitive (0.1% mutation abundance), and efficient (18 targets in parallel) “bedside testing” of drug-related genetic markers. They developed 3D cultured organoids to predict drug response, constructing models for 14 diseases, including systemic sclerosis, inflammatory bowel disease, and ovarian cancer, to implement fine stratification of drug resistance risks in chronic disease patients. They created a new single-point methylation detection technology and a precise treatment strategy based on SLC22A2 methylation dynamic modification to reverse tumor resistance, achieving “targeted intervention.” Seventeen genetic mutation detection kits developed based on the innovative precise medication system have obtained national second and third class product registration certificates, serving 800,000 chronic disease patients and significantly improving treatment outcomes.
Establishing a New Drug Clinical Positioning Technology System and a New Drug Development Paradigm Through Evidence-Based Guidance, Pharmacological Exploration, and Clinical Validation
The team discovered that over 35.7% of rheumatoid arthritis patients had poor responses to methotrexate, the cornerstone drug, 37% discontinued treatment due to adverse reactions, and 33% experienced worsened organ damage and poor prognosis after disease relapse, revealing a significant treatment gap. This led to the proposal of an innovative treatment strategy focusing on inflammation control and target organ protection. Pharmacological exploration revealed that ailanthus altissima extract has unique pharmacological properties different from traditional nonsteroidal anti-inflammatory drugs, with significant anti-inflammatory, immunomodulatory, and bone-protective activities, precisely matching the multi-target treatment needs of rheumatoid arthritis. The team led national multi-center clinical studies for innovative clinical positioning in phases II and III, successfully achieving the market approval of ailanthus altissima extract, the only new class 1.1 drug approved in the rheumatology field in nearly ten years in China. The drug has generated sales of 4.39 billion RMB over the past three years, saving approximately 1.3 billion RMB in annual drug costs, achieving significant economic and social benefits. The new drug clinical positioning technology system developed by the team has significantly accelerated innovative drug development, discovering over 100 novel lead molecules for anti-tumor, anti-inflammatory, and immunomodulatory applications. They have obtained four candidate drugs with independent intellectual property rights, including anti-tumor metastasis YH-Z-02, hypoglycemic candidate A6, anti-tumor resistance UAT-B, and anti-lung cancer stem cell AP-7, with system evaluation completed for anti-tumor drugs YH-Z-2 and UAT-B, which are about to enter clinical development.
Facing the severe challenges of chronic disease management in China, clinical pharmacy is increasingly demonstrating its unique value in providing robust technical support for rational and precise medication use. It plays a vital role in optimizing healthcare resource allocation and reducing medical costs. The new drug development paradigm led by clinical pharmacy will further enhance research and development efficiency, shorten development cycles, and produce more clinically valuable drugs. In summary, clinical pharmacy will play an increasingly important role in the future development of medicine, contributing significantly to the health of humanity.
