Commentary—Oral MS Therapies Show Promise and Raise Questions

Ludwig Kappos’s assessment of approved and emerging oral disease-modifying therapies (DMTs) for multiple sclerosis and his comparison of these medicines with injectable therapies nicely summarizes efficacy and safety data for fingolimod, dimethyl fumarate, teriflunomide, and laquinimod.

Although these drugs were primarily compared to placebo in pivotal trials, all were also compared with injectable DMTs. Dimethyl fumarate was compared with glatiramer acetate, fingolimod and laquinimod were compared with intramuscular interferon beta-1a, and teriflunomide was compared with a high dose of subcutaneous interferon beta-1a.

Some clinical and MRI outcomes significantly favored fingolimod over interferon beta 1-a, whereas laquinimod did not demonstrate superiority to the latter drug. Dimethyl fumarate also showed a significant reduction in relapse rate in the 240-mg tid dosage group (but not in the 240-mg bid group) and on some MRI indicators, compared with glatiramer acetate. None of these drugs, however, showed a benefit versus a comparator on disability progression. In most instances, the comparator data did not reflect the primary outcome of the trial.

The best way to compare efficacy is by well-designed, head-to-head trials. Such studies require a large number of patients and are expensive to carry out. Whether such studies will eventually be initiated remains to be seen. Although preliminary evidence from the oral drug pivotal trials suggests the comparative efficacy of each, more studies are clearly needed. It is worth remembering that not all the injectable DMTs have the same effect on MRI or clinical outcomes, which must be considered when comparison studies are carried out.

Lastly, it is still early in the assessment of the relative safety of oral drugs, safety being the other major factor in drug assessment. On the other hand, the interferons and glatiramer acetate have been shown to have excellent safety records over long periods of time.