The contribution of multiple sclerosis relapses to worsening of disability, and vice-versa, remains unclear. Vitamin D supplementation (VitD) and disease modifying therapies (DMTs) are potential modulators of this association. Understanding how these endo-phenotypes interact may provide insights to disease pathogenesis and treatment practice. Here, we examined independent associations between relapses and treatment and the risk of worsening of disability, and vice-versa. We find suggestive evidence that early relapses predict early worsening of disability but do not contribute to long-term worsening. Conversely, the effects of worsening of disability on relapse risk was pronounced and persisted. VitD and DMTs interacted significantly to markedly reduce the risk of future relapses and worsening of disability, particularly when commenced early. Personalised real-time survival probabilities revealed individuals having higher risk of future worsening. Worsening of disability in ROMS occurs in ways not clearly tied to relapses and is strongly linked to an increased risk of future relapses.
