Ocrelizumab treatment for relapsing-remitting multiple sclerosis after a suboptimal response to previous disease-modifying therapy: A nonrandomized controlled trial

Abstract

Background: Many patients with multiple sclerosis (MS) experience suboptimal disease control despite the use of disease-modifying therapy (DMT). Objective: To assess the efficacy and safety of ocrelizumab (OCR) in patients with relapsing-remitting MS (RRMS) and suboptimal response to prior DMTs. Methods: Patients with RRMS and suboptimal responses (one clinically reported relapse and/or lesion activity) after ⩾ 6 months on another DMT were enrolled. OCR 600 mg was given intravenously every 24 weeks. The primary outcome was no evidence of disease activity (NEDA), defined as the absence of protocol-defined relapse, confirmed disability progression (CDP), T1 Gd-enhancing lesions, and new/enlarging T2 lesions. Results: The intention-to-treat (ITT) population included 608 patients; NEDA was analyzed in a modified ITT (mITT) population ( n = 576 (94.7%)). Over 96 weeks, 48.1% of mITT patients achieved NEDA, and most were free from protocol-defined relapse (89.6%), CDP (89.6%), and T1 Gd-enhancing lesions (95.5%); 59.5% had no new/enlarging T2 lesions. Safety observations were consistent with findings in the pivotal trials. Conclusion: Consistent efficacy of OCR on clinical and magnetic resonance imaging (MRI) disease activity measures and progression was shown in patients with RRMS and a suboptimal response to prior DMTs; no new safety signals were observed.

Ocrelizumab: A Review in Multiple Sclerosis

“…2.1.2 ) [ 11 ], in addition to interim data from ongoing phase IIIb or IV trials in patients with treatment-naïve, early stage RRMS (ENSEMBLE [ 12 ]) and RMS previously treated with natalizumab (ENCORE [ 13 ]). The specific efficacy of ocrelizumab in patients with RRMS and a suboptimal response to prior DMTs has been investigated in two open-label, single-arm, multicentre phase IIIb studies (CHORDS in North America [ 14 ] and CASTING in the EU [ 15 ]; Sect. 2.1.3 ).…”

“…CASTING [ 15 ] and CHORDS [ 14 ] enrolled patients aged 18–55 years with a diagnosis of RRMS (based on the 2010 revised McDonald criteria), a disease duration from first symptom of < 10 years [ 15 ] or ≤ 12 years [ 14 ] and a screening EDSS score of 0.0–4.0 [ 15 ] or 0.0–5.5 [ 14 ]. Eligible patients had received ≤ 2 [ 15 ] or ≤ 3 [ 14 ] other DMTs prior to screening and had discontinued the most recent adequately used DMT due to suboptimal disease control [ 14 , 15 ].…”

“…CASTING [ 15 ] and CHORDS [ 14 ] enrolled patients aged 18–55 years with a diagnosis of RRMS (based on the 2010 revised McDonald criteria), a disease duration from first symptom of < 10 years [ 15 ] or ≤ 12 years [ 14 ] and a screening EDSS score of 0.0–4.0 [ 15 ] or 0.0–5.5 [ 14 ]. Eligible patients had received ≤ 2 [ 15 ] or ≤ 3 [ 14 ] other DMTs prior to screening and had discontinued the most recent adequately used DMT due to suboptimal disease control [ 14 , 15 ]. In both trials, patients received ocrelizumab 600 mg (administered as two 300 mg infusions on days 1 and 15 for the initial dose and a single 600 mg infusion thereafter) every 24 weeks for 96 weeks ( n = 680 evaluated in CASTING and 576 in CHORDS).…”

“…In both trials, patients received ocrelizumab 600 mg (administered as two 300 mg infusions on days 1 and 15 for the initial dose and a single 600 mg infusion thereafter) every 24 weeks for 96 weeks ( n = 680 evaluated in CASTING and 576 in CHORDS). The primary endpoint was NEDA (with prespecified MRI re-baselining at week 8 [ 15 ]), defined as the absence of 24-week CDP, protocol-defined relapse, gadolinium-enhancing T 1 lesions and new or enlarging T 2 lesions, over 96 weeks [ 14 , 15 ].…”

“…The proportion of ocrelizumab recipients with NEDA over 96 weeks was 48.1% in CHORDS [ 14 ] and 74.8% (with MRI re-baselining at week 8) in CASTING [ 15 ]. Most patients were free from 24-week CDP (89.6% in CHORDS and 87.5% in CASTING), protocol-defined relapses (89.6% and 89.8%), gadolinium-enhancing T 1 lesions (95.5% and 97.7%) and new or enlarging T 2 lesions (59.5% and 91.5%) [ 14 , 15 ].…”