From the Guidelines
Primary Progressive Multiple Sclerosis (PPMS) treatment should focus on managing symptoms and slowing disease progression with Ocrelizumab (Ocrevus) as the only FDA-approved medication specifically for PPMS, administered as an intravenous infusion every six months. The treatment approach for PPMS is multifaceted, aiming to improve quality of life and reduce morbidity and mortality.
Key Treatment Components
- Medications:
- Ocrelizumab for disease modification
- Baclofen or tizanidine for spasticity
- Amantadine for fatigue
- Gabapentin or pregabalin for neuropathic pain
- Anticholinergics like oxybutynin for bladder dysfunction
- Therapies:
- Physical therapy to maintain mobility and strength
- Occupational therapy for daily activities
- Speech therapy for speech or swallowing difficulties
- Lifestyle:
- Healthy diet
- Regular exercise within capabilities
- Stress management
- Adequate rest
As noted in the study by 1, the diagnosis of PPMS can be challenging, particularly with normal brain MRI and inconclusive spinal cord findings, highlighting the importance of a comprehensive diagnostic approach. The 2010 McDonald criteria, discussed in 1, have improved the diagnostic process but exhibit limitations in PPMS, emphasizing the need for careful clinical evaluation and paraclinical support. Given the complexity of PPMS and its resistance to treatment compared to relapsing forms of MS, regular follow-up with a neurologist is essential to monitor disease progression and adjust treatment as needed.
From the FDA Drug Label
OCREVUS ZUNOVO is indicated for the treatment of: ... Primary progressive MS, in adults The efficacy of intravenous ocrelizumab was demonstrated in ... patients with relapsing forms of multiple sclerosis (RMS) ... The dose of intravenous ocrelizumab was 600 mg every 24 weeks
- Treatment for PPMS: Ocrelizumab (IV) is indicated for the treatment of Primary Progressive MS (PPMS) in adults.
- Dosage: The dose of intravenous ocrelizumab is 600 mg every 24 weeks 2 2
From the Research
Treatment for Primary Progressive Multiple Sclerosis (PPMS)
- Ocrelizumab is an approved treatment for adults with PPMS, which has been shown to reduce measures of clinical and MRI progression relative to placebo 3, 4.
- The efficacy of ocrelizumab in PPMS was demonstrated in a phase 3 trial, where it was associated with lower rates of clinical and MRI progression than placebo 4.
- Ocrelizumab is generally well-tolerated, with a safety profile consistent with its known effects, and no new safety signals have emerged with long-term use 3, 5.
- Real-world data from a compassionate use program in Germany supports the safety and efficacy of ocrelizumab in patients with PPMS, with a low rate of adverse events and no significant differences in serious adverse events or serious infections compared to placebo 5.
Mechanism of Action and Pharmacokinetics
- Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20-expressing B cells, which has been shown to be effective in reducing disease activity in patients with PPMS 6, 4.
- The pharmacokinetics of ocrelizumab have been characterized in patients with RMS and PPMS, with a terminal half-life of approximately 26 days and a time-dependent clearance 7.
- Body weight is a significant covariate affecting the pharmacokinetics of ocrelizumab, with higher exposure and greater B-cell depletion observed in patients with lower body weight 7.
Clinical Benefits and Outcomes
- Ocrelizumab has been shown to slow disease progression in patients with PPMS, with significant reductions in the risk of 12-week and 24-week confirmed disability progression 4.
- Treatment with ocrelizumab has also been associated with improvements in MRI outcomes, including reduced total volume of brain lesions and decreased brain-volume loss 4.
- The clinical benefits of ocrelizumab in PPMS have been maintained over long-term treatment, with no significant differences in adverse events or serious infections compared to placebo 3, 5.