Background: Patient-centred care is essential for effectively managing relapsing multiple sclerosis (RMS). The PROFILE-RMS study aimed to characterise unmet medical needs using clinically meaningful patient profiles. Methods: This 12 month observational study collected real-world data across Germany. Adults with RMS receiving disease-modifying therapy (DMT) were classified into predefined profiles: ongoing disease activity (Profile 1), significant adverse drug reactions (ADRs; Profile 2), or low treatment satisfaction (Profile 3). Outcomes included treatment response, disease activity, patient-reported outcomes (PROs), and safety. Results: In total, 488 patients were analysed. In Profile 1 (n = 246), 41.6% had insufficient response to therapy, with severe fatigue identified as an indicator (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.12–3.88), but only 14.2% changed treatment (mainly for disease activity); 4.1% experienced a serious adverse event (SAE). In Profile 2 (n = 179), 31.5% had insufficient response, but only 18.4% changed treatment (mainly for disease activity); 1.6% experienced an SAE. In Profile 3 (n = 63), 33.3% had insufficient response, with male sex identified as an indicator (HR: 3.09; 95% CI: 1.40–6.82), but only 17.5% changed treatment (mainly for low satisfaction); 1.6% experienced an SAE. Across profiles, most patients received low-moderate efficacy DMTs, the percentage of patients without DMTs increased, and PROs were impaired. Conclusions: Patient profiling highlights gaps in real-world RMS management, where DMTs are often discontinued without substitution and escalation to high-efficacy regimens often delayed, reinforcing the need for patient-centred care. Fatigue may indicate non‑response (Profile 1), disease activity outweighs ADR burden (Profile 2), and symptom load drives dissatisfaction (Profile 3). Trial registration: Protocol number ML39348.