CURE: a phase-based therapeutic framework for chronic inflammation.

Background: Chronic inflammation represents a central mechanism underlying the persistence of immune-mediated diseases. Unlike acute inflammation, which resolves through coordinated regulatory checkpoints and active resolution programs, chronic inflammation stabilizes in pathological states maintained by cytokine redundancy, tissue-resident immune memory, and self-reinforcing feedback loops that resist termination. Conceptual framework: Here, we introduce the CURE framework (CONTROL - UNLOAD and RESET - EQUILIBRATE), a phase-based therapeutic model grounded in systems immunology and nonlinear dynamics. The acronym is used as a mnemonic for the proposed therapeutic sequence and does not imply curative eradication of chronic inflammatory disease. Rather, the framework addresses durable disease control, relapse prevention, and stabilization of functional remission. CURE is proposed as a conceptual, phase-based framework that interprets treatment as dependent on the cumulative intensity and duration of anti-inflammatory therapeutic exposure across three clinically relevant phases. Within this hypothesis, CONTROL refers to sufficiently intensive induction therapy intended to suppress self-sustaining inflammatory circuits and potentially cross clinically relevant inflammatory thresholds. UNLOAD and RESET describe a structured, guided de-escalation phase that consolidates remission while restoring endogenous resolution mechanisms. EQUILIBRATE represents proactive, low-amplitude maintenance aimed at stabilizing long-term immune equilibrium and preventing relapse. Systems perspective and evidence synthesis: From a complex systems perspective, durable disease control may depend not solely on dose selection but also on whether therapeutic exposure is sufficient to suppress feedback-driven immune networks below clinically relevant thresholds. The CURE framework integrates mechanistic and clinical evidence across multiple immune-mediated conditions-including atopic dermatitis, psoriasis, inflammatory bowel disease, and rheumatoid arthritis-to illustrate shared immunodynamic principles underlying durable disease control. Conclusions: By aligning therapeutic intensity with the dynamic state of the immune system, CURE may provide a transferable, mechanism-oriented framework for personalized intervention in chronic inflammation. It reframes disease management from reactive symptom driven suppression toward proactive, phase-specific immune stabilization. It further offers a common conceptual language across specialties, supporting functional remission, relapse prevention, and long-term tissue integrity.