Systemic Recombinant Human Interferon-β Treatment of Relapsing–Remitting Multiple Sclerosis: Pilot Study Analysis and Six-Year Follow-Up

Abstract

A pilot study was undertaken to test the safety and establish the side effect profile of recombinant human interferon-beta 1b (Betaseron, Berlex Laboratories, Richmond, CA), in patients with relapsing-remitting multiple sclerosis (RRMS). During the initial dose finding period (24 weeks), five groups of 6 patients each were treated by subcutaneous injection three times each week with either 0.8, 4, 8, or 16 million units (mU) of Betaseron or placebo (WHO Standard). Although some side effects were noted in all groups, a dose-related trend in reduction of exacerbation frequency and side-effect profile was noted. Patients given 16 mU had no exacerbations during the initial dosing period, but associated side effects led to dose reduction or dropout. An 8 mU dose was selected for further study after 24 weeks, and continuous dosing at 8 mU in 15 patients has now exceeded 6 years. Side effects abated over time. Neutralizing antibody developed in most patients, but titers were variable, fluctuated independently of clinical course, and tended to fall with prolonged treatment. A dose-dependent rise in neopterin levels was observed during the initial dosing period. This pilot study has demonstrated responsiveness to Betaseron, shown a stable safety profile over time, and established guidelines for a dosing regimen to evaluate and optimize further the efficacy of Betaseron in RRMS.

Clinical effectiveness and cost-effectiveness of beta-interferon and glatiramer acetate for treating multiple sclerosis: systematic review and economic evaluation

“…Similar findings based on final data were reported, but only a p-value (p = 0.012) for a relationship in the same direction was provided. Knobler et al 211 did not find a significant relationship for 'attack severity', although the findings were reported only as a non-significant p-value (p = 0.67) and relapse severity was not defined.…”

“…[170][171][172][174][175][181][182][183][184][185][186]188,190,192,[195][196][197][198][199]209,211,213,[216][217][219][220][221][222][223][224] Fourteen studies, most of which were comparisons between different active drugs, specifically did not blind participants or practitioners; 170,[182][183][184][185][186]188,190,192,[195][196][197]199,216 in another 15 studies, participants were initially blinded but were at high risk of unblinding from increased rates of side effects. [171][172][174][175]…”

“…171,175,189,192,198,[222][223][224] In nine cases, outcome assessors were otherwise blinded but injection sites were not covered and these studies were designated to be at high risk of bias. 170,174,184,209,211,213,[216][217]219 Additionally, studies in which participants were unblinded were designated as being at high risk of bias for outcome assessment if they did not report that participants were given specific instructions against sharing treatment information with assessors. 170,[182][183][184][185][186]188,190,192,[195][196][197][198][199]216 All studies that reported MRI outcomes and detailed methods for blinding of MRI assessment were found to be at low risk of bias (n = 13/15).…”

“…[209][210][211] Schwartz et al 181 examined QoL outcomes only and used BSC as the comparator instead of placebo.…”

Early stage and long term treatment of multiple sclerosis with interferon-β

“…25 Thirty RRMS patients were randomized to receive 0.8, 4, 8, or 16 million international units (MIU) of IFNβ-1b or placebo via subcutaneous (SC) injection administered three times per week (TIW). The 8 MIU dose was reasonably well tolerated; however, the 16 MIU caused excessive side effects.…”