## 4 Discussion
FM patients face a high RPO, influenced by the intricate interplay of clinical characteristics and prognostic factors, including physical (e.g., pain, disability), psychological (e.g., depression, anxiety, catastrophizing), and social factors (e.g., employment, economic strain, isolation) [73; 74; 75]. FM itself is associated with reduced satisfaction, increased pain, poorer functional outcomes, higher opioid use, and an increase in post-orthopedic surgery complications [74; 76]. Our preliminary study is the first to explore the use of the KSMT to stratify FM patients based on baseline risk, as EULAR promotes its generic use [42]. Interestingly, only 18% of participants in our sample did not show a positive change in risk scores after the iVRE protocol, all of whom had a high baseline RPO. Future well-designed studiesshould validate KSMT as a reliable predictive tool for treatment response in FM and explore its potential in guiding personalized therapeutic approaches. Additionally, our study opens the door for future research to investigate whether iVRE can positively influence other key prognostic indicators, further expanding treatment options for FM. While the primary focus of this study was to explore the preliminary clinical outcomes of the intervention protocol, feasibility indicators were also reported. The enrollment rate was 1.44 patients per week, the recruitment rate was 76.92%, and the retention rate was 55%. The relatively low retention rate was attributed to unavoidable non-clinical circumstances, including personal reasons, scheduling conflicts, and difficulties in rescheduling, all consistent with the study's protocol requirements. Importantly, no adverse events were reported throughout the study. Although the intervention was well tolerated and executed as planned, suggesting no necessary protocol adjustments, future studies could enhance retention by offering more flexible scheduling options (such as evening or weekend sessions), implementing contingency plans for rescheduling missed sessions, and considering similar apps with audible stimuli (e.g., music) or remote delivery options to address motivational, weather-related, or accessibility barriers. These adaptations would help minimize non-compliance and improve overall participant retention. The limitations of the study include: (i) the absence of a control group, which introduces potential confounding bias in the results; (ii) the sample size was not probabilistically estimated, implying a potential limitation in statistical power; (iii) due to the small sample size, exploratory nature, and single-arm design, statistical inferences and external validity cannot be assured, limiting the generalizability of the results. However, these design choices were based on the novelty of the intervention and the lack of prior studies evaluating iVRE protocols targeting endogenous analgesic mechanisms or prognostic stratification in FM. Additionally, the low retention rate of 55% may influence the internal validity of the study; (iv) despite no reported adverse health events, the low retention rate highlights the need for more flexible scheduling to reduce dropout; (v) the study lacked long-term follow-up; (vi) although a survey format was used to assess the most frequently reported adverse events in the literature, the tool employed has not been validated; (vii) psychosocial factors such as kinesisophobia, catastrophizing, and motivation were not considered in this exploratory study, which may have influenced results and participant engagement; (viii) quantitative sensory testing was not employed to further assess pain mechanisms; and (ix) there were selection biases that may affect the generalizability of the findings. Adherence bias was present, as only participants who completed the intervention were analyzed. Additionally, recruitment from a patient association may limit the representativeness of the sample, and volunteer bias could introduce baseline differences or more favorable outcome expectations.