‘The uncertainty continues’
“These differences that we see in the effectiveness can be somewhat surprising, especially when it comes to natalizumab,” which is considered very effective, said Mr. Alping. The vulnerable period that occurs after switching from natalizumab may partly explain the difference. “This is something to keep in mind when starting patients on natalizumab treatment in the clinic,” Mr. Alping added.
Although rituximab is not indicated for MS, many clinics are using it in this population, said Robert Fox, MD, staff neurologist at the Mellen Center for MS and vice chair for research at the Neurological Institute of Cleveland Clinic, both in Cleveland, Ohio. Dr. Fox was not involved in the study.
“Assessing the generalizability of the study outside Sweden will be important,” he added, “but I would be surprised if their findings did not hold up to external validation.”
The way that the researchers addressed missing data could affect the interpretation of the findings. “Depending upon how much data was missing, their imputation methods may have a high level of uncertainty,” said Dr. Fox.
The researchers’ adjustments for baseline differences also raise questions. “Even though MRI was an outcome, it doesn’t appear they adjusted for baseline differences in MRI between the groups,” Dr. Fox observed.
Moreover, the study was conducted over a long period of time. “We know there are time effects in MS, with a very different disease activity expected from patients over time,” said Dr. Fox. For example, relapse rates in placebo groups of MS trials tend to decline over time. “This time effect likely impacted their results.”
But the disability findings may be the most important part of the study, according to Dr. Fox. The lack of significant difference in disability progression between therapies “highlights that a couple relapses or lesions on MRI may be too small to translate into long-term differences in disability progression,” he said.
“The long-term implications of small differences in relapse and MRI outcomes may be very small,” Dr. Fox went on. “Thus, the uncertainty continues around escalation treatment versus initial highly effective treatment paradigms.”
The Patient-Centered Outcomes Research Institute, the Swedish Research Council, and NEURO Sweden funded this study. Mr. Alping disclosed no relevant financial relationships. Dr. Fox receives consulting fees from the companies that manufacture all the therapies analyzed in the study.
A version of this article first appeared on Medscape.com.