Cardiff University

Author Of 1 Presentation

Clinical Outcome Measures Poster Presentation

P0128 - Outcomes in Alemtuzumab-Treated Patients With Thyroid Adverse Events: 6-Year Pooled CARE-MS Data (ID 736)

Abstract

Background

Over 6 years in the CARE-MS core and extension trials (NCT00530348; NCT00548405; NCT00930553), alemtuzumab improved outcomes in RRMS patients, but many experienced thyroid adverse events (AEs).

Objectives

To characterize thyroid AEs over 6 years in alemtuzumab-treated patients from the CARE-MS core and extension trials.

Methods

Patients received 2 alemtuzumab courses, with as-needed additional alemtuzumab ≥12 months after the most recent course. An expert panel of 3 independent endocrinologists reviewed all reported cases of thyroid-related laboratory abnormalities and AEs to assess diagnosis, start date, and outcome through a consensus approach. Cases for which consensus was not reached, or those that were preexisting or occurred after Y6 were excluded.

Results

Over 6 years, 378/811 (47%) alemtuzumab-treated patients had a thyroid AE or laboratory abnormality (342 [42%] with thyroid AE; 44 serious AEs). After panel review, 292 cases had a consensus diagnosis as a thyroid AE, no consensus diagnosis could be reached in 60 cases, 2 cases were deemed pre-existing, and 24 occurred after Y6. Cases with a consensus diagnosis were adjudicated to Graves’ disease (40%), Hashimoto’s disease (17%), transient thyroiditis (8%), Graves’ disease switching to hypothyroidism (6%), Hashimoto’s disease switching to hyperthyroidism (3%), or uncertain (27%). Oral thyroid medications were given to 245/292 (84%) patients, primarily levothyroxine/levothyroxine sodium (n=187; 64%) or thiamazole (n=126; 43%); 32/292 (11%) patients underwent thyroidectomy and 26/292 (9%) underwent radioiodine therapy. Within 2 years of the last alemtuzumab course, 83% of thyroid AEs appeared (>97% were detected within 4 years). Patients with vs without thyroid AEs received similar numbers of alemtuzumab courses (2 courses: 62% vs 60% of patients; 3 courses: 24% in each group). From baseline to Y6, MS disease outcomes were similar in patients with vs without thyroid AEs (annualized relapse rate: 0.20 vs 0.21; mean EDSS score change: −0.04 vs +0.08; proportion with stable/improved EDSS scores: 81% vs 80%; proportions MRI disease activity-free: 60%-78% per year vs 60%-76% per year; and median cumulative brain volume loss: −1.11% vs −1.27%). Outcomes as of last follow-up were recovered (53%), ongoing (46%), and unknown (0.3%).

Conclusions

Graves’ disease was the most common thyroid AE. Most thyroid AEs were treated with oral medications. No differences in 6-year MS disease outcomes were seen when comparing patients with or without thyroid AEs.

STUDY SUPPORT: Sanofi and Bayer Healthcare Pharmaceuticals.

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