Multiple sclerosis in older adults: the clinical profile and impact of interferon Beta treatment

Abstract

Background: We examined (1) patient characteristics and disease-modifying drug (DMD) exposure in late-onset (LOMS, ≥50 years at symptom onset) versus adult-onset (AOMS, 18-<50 years) MS and (2) the association between interferon-beta (IFNβ) and disability progression in older relapsing-onset MS adults (≥50 years).

Methods: This retrospective study (1980-2004, British Columbia, Canada) included 358 LOMS and 5627 AOMS patients. IFNβ-treated relapsing-onset MS patients aged ≥50 (regardless of onset age, 90) were compared with 171 contemporary and 106 historical controls. Times to EDSS 6 from onset and from IFNβ eligibility were examined using survival analyses.

Results: LOMS patients (6%) were more likely to be male, with motor onset and a primary-progressive course, and exhibit faster progression and were less likely to take DMDs. Nonetheless, 57% were relapsing-onset, of which 31% were prescribed DMDs, most commonly IFNβ. Among older relapsing-onset MS adults, no significant association between IFNβ exposure and disability progression was found when either the contemporary (hazard ratio [HR]: 0.46; 95% CI: 0.18-1.22) or historical controls (HR: 0.54; 95% CI: 0.20-1.42) were considered.

Conclusion: LOMS differed clinically from AOMS. One-third of older relapsing-onset MS patients were prescribed a DMD. IFNβ exposure was not significantly associated with reduced disability in older MS patients.

Figures

Figure 1

Multivariable Cox regression analysis of potential factors associated with time to reach confirmed and sustained EDSS 6 from onset of MS symptoms in patients with relapsing-onset (a) and primary-progressive (b) MS.  ∗Out of 5373 patients with relapsing-onset MS, 874 patients did not contribute to the analysis (i.e., were excluded from the analyses). Those included 640 patients who had already reached the outcome by first clinic assessment (i.e., were left-censored), 185 patients with no EDSS score recorded, and 49 patients who were censored before the earliest event. †Reference level = absence of the specific onset symptom. ‡Out of 612 patients with primary-progressive MS, 273 patients did not contribute to the analysis (including 234 patients who had already reached the outcome by first clinic assessment (i.e., left-censored), 33 patients with no EDSS score recorded, and 6 patients who were censored before the earliest event).

Figure 2

Selection of the interferon beta-treated and untreated cohorts aged ≥50 at interferon beta eligibility date. BCMS clinic, British Columbia Multiple Sclerosis clinic; DMD, disease-modifying drug; EDSS, Expanded Disability Status Scale; RRMS, relapsing-remitting multiple sclerosis; and SPMS, secondary progressive multiple sclerosis.  ∗The sum of the individual reasons (numbers) exceeds the total number of patients in some boxes because some patients met more than one condition.

Figure 3

Multivariable time-dependent Cox regression analysis of potential factors affecting time to reach confirmed and sustained EDSS 6 for 90 interferon beta-exposed patients versus 171 contemporary controls aged ≥50 at baseline, with interferon beta treatment as a time-varying covariate (a). Results of the same analysis for 90 interferon beta-exposed patients and 106 historical controls (b).  ∗Ten patients who were censored before the earliest event did not contribute to the analysis. †266 person-years of interferon beta exposure and 151 person-years of untreated time (92 person-years before and 59 person-years after the initiation of interferon beta treatment). ‡597 person-years of untreated time. §Seven patients who were censored before the earliest event did not contribute to the analysis. ||694 person-years of untreated time.