Author Of 1 Presentation
PS01.04 - Comparison of disability trajectories in relapsing Multiple Sclerosis patients treated with early intensive or escalation treatment strategies
- P. Iaffaldano
- G. Lucisano
- F. Caputo
- D. Paolicelli
- F. Patti
- M. Zaffaroni
- V. Brescia Morra
- C. Pozzilli
- G. De Luca
- M. Inglese
- G. Salemi
- C. Florio
- E. Cocco
- P. Sola
- G. Lus
- A. Conte
- M. Amato
- F. Granella
- S. Galgani
- D. Centonze
- R. Totaro
- M. Rovaris
- M. Salvetti
- R. Mantegazza
- R. Bergamaschi
- D. Maimone
- E. Scarpini
- A. Bertolotto
- G. Comi
- M. Filippi
- M. Trojano
Abstract
Background
to date, no consensus exists on how aggressively and timely treat relapsing-remitting multiple sclerosis (RRMS) patients.
Objectives
To evaluate disability trajectories in a cohort of RRMS patients stratified according to two different disease modifying therapy (DMT) strategies, early intensive treatment (EIT) or moderate-efficacy treatment followed by escalation to higher-efficacy DMT (ESC).
Methods
RRMS patients with ≥5-year follow-up and ≥3 visits after start DMT, and a first visit within 3 years from disease onset were selected from the Italian MS Registry. EIT group included patients who received, as first DMT, fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group included those who received the high efficacy DMT after ≥1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score(PS)-matched for characteristics at the first DMT. The follow-up time from the first DMT start has been segmented into 12-month periods. The disability trajectories were evaluated by applying a longitudinal model for repeated measures with an autoregressive variance-covariance structure. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual EDSS changes compared to baseline values (delta-EDSS) in EIT and ESC groups.
Results
The study cohort included 2,652 RRMS patients from 62 Italian MS centers. The PS matching procedure produced 365 pairs. The median (IQR) follow-up after the first DMT start was 8.5 (6.5–11.7) years. All of the ESC patients escalated to a higher-efficacy DMT after a median time of 5.1 (3.1–8.4) years. The estimated baseline EDSS with relative confidence interval (95% CI) value was 2.52 (2.33-2.71) in the ESC group and 2.45 (2.26-2.64) in the EIT group. Mean delta-EDSS at each 12 month period were all significantly (p<0.02) higher in the ESC group compared to the EIT group. In particular, the mean delta-EDSS differences between the two groups tend to increase from 0.1 (0.01-0.19, p=0.03) at 1 year to 0.30 (0.07-0.53, p=0.009) at 5 years and to 0.67 (0.31-1.03, p=0.0003) at 10 years.
Conclusions
Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression and the effect tends to increase over time despite patients in the ESC group escalated to a higher-efficacy DMT.
Author Of 1 Presentation
P0752 - Safety of eculizumab in NMOSD and MG – analysis of the phase 3 studies PREVENT and REGAIN and their extensions (ID 554)
Abstract
Background
Aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD) and acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ gMG) are neurological disorders with complement involvement. Eculizumab (a terminal complement inhibitor) demonstrated efficacy in reducing relapse risk and in eliciting clinical improvements during the phase 3, randomized, double-blind PREVENT and REGAIN studies and their open-label extensions (OLEs) (NCT01892345/NCT02003144 [interim data, July 2019] and NCT01997229/NCT02301624) previously published.
Objectives
To compare infection rates in patients with AQP4+ NMOSD or AChR+ gMG receiving eculizumab or placebo with or without concomitant immunosuppressive therapy (IST) during PREVENT, REGAIN and their OLEs.
Methods
Patients were randomized to eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo. Concomitant ISTs, excluding rituximab, were permitted. Post hoc analysis was performed to examine rates of infections in these studies and for subgroups determined by number of ISTs received at baseline.
Results
Rates/100 patient-years (PY) and types of infection were similar in eculizumab and placebo groups. In patients with NMOSD, rates/100 PY and % (n/N), respectively, were: no IST: 176.1, 80.0% (28/35) vs 192.2, 61.5% (8/13); 1 IST: 171.5, 81.8% (45/55) vs 154.1, 63.6% (14/22); 2 ISTs: 186.7, 85.1% (40/47) vs 238.2, 83.3% (10/12). For patients with gMG, rates/100 PY and % (n/N), respectively, were: no IST: 236.8, 100.0% (2/2) vs 305.6, 50.0% (1/2); 1 IST: 228.8, 82.9% (34/41) vs 253.1, 50.0% (9/18); 2 ISTs: 170.5, 91.0% (71/78) vs 192.5, 58.5% (24/41); ≥ 3 ISTs: 97.5, 50.0% (1/2) vs 100.1, 50.0% (1/2). In patients with NMOSD or gMG receiving eculizumab vs placebo, serious infection rates/100 PY and % (n/N), respectively, were: no IST: 2.3, 5.7% (2/35) vs 8.0, 7.7% (1/13) and none observed (0/2 vs 0/2); 1 IST: 11.2, 16.4% (9/55) vs 7.0, 9.1% (2/22) and 16.2, 24.4% (10/41) vs 34.5, 5.6% (1/18); 2 ISTs, 14.8, 29.8% (14/47) vs 47.6, 25.0% (3/12) and 13.4, 21.8% (17/78) vs 24.1, 12.2% (5/41); ≥ 3 ISTs (gMG only), 13.9, 50.0% (1/2) vs 0.0, 0.0% (0/2). One patient with gMG (2 ISTs) had meningococcal meningitis that resolved with antibiotics and eculizumab was resumed.
Conclusions
In AQP4+ NMOSD and AChR+ gMG, infection rates/100 PY were similar in eculizumab and placebo groups, regardless of concomitant IST. Infection rates/100 PY were consistent with the established safety profile of eculizumab.
Presenter Of 1 Presentation
P0752 - Safety of eculizumab in NMOSD and MG – analysis of the phase 3 studies PREVENT and REGAIN and their extensions (ID 554)
Abstract
Background
Aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD) and acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ gMG) are neurological disorders with complement involvement. Eculizumab (a terminal complement inhibitor) demonstrated efficacy in reducing relapse risk and in eliciting clinical improvements during the phase 3, randomized, double-blind PREVENT and REGAIN studies and their open-label extensions (OLEs) (NCT01892345/NCT02003144 [interim data, July 2019] and NCT01997229/NCT02301624) previously published.
Objectives
To compare infection rates in patients with AQP4+ NMOSD or AChR+ gMG receiving eculizumab or placebo with or without concomitant immunosuppressive therapy (IST) during PREVENT, REGAIN and their OLEs.
Methods
Patients were randomized to eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo. Concomitant ISTs, excluding rituximab, were permitted. Post hoc analysis was performed to examine rates of infections in these studies and for subgroups determined by number of ISTs received at baseline.
Results
Rates/100 patient-years (PY) and types of infection were similar in eculizumab and placebo groups. In patients with NMOSD, rates/100 PY and % (n/N), respectively, were: no IST: 176.1, 80.0% (28/35) vs 192.2, 61.5% (8/13); 1 IST: 171.5, 81.8% (45/55) vs 154.1, 63.6% (14/22); 2 ISTs: 186.7, 85.1% (40/47) vs 238.2, 83.3% (10/12). For patients with gMG, rates/100 PY and % (n/N), respectively, were: no IST: 236.8, 100.0% (2/2) vs 305.6, 50.0% (1/2); 1 IST: 228.8, 82.9% (34/41) vs 253.1, 50.0% (9/18); 2 ISTs: 170.5, 91.0% (71/78) vs 192.5, 58.5% (24/41); ≥ 3 ISTs: 97.5, 50.0% (1/2) vs 100.1, 50.0% (1/2). In patients with NMOSD or gMG receiving eculizumab vs placebo, serious infection rates/100 PY and % (n/N), respectively, were: no IST: 2.3, 5.7% (2/35) vs 8.0, 7.7% (1/13) and none observed (0/2 vs 0/2); 1 IST: 11.2, 16.4% (9/55) vs 7.0, 9.1% (2/22) and 16.2, 24.4% (10/41) vs 34.5, 5.6% (1/18); 2 ISTs, 14.8, 29.8% (14/47) vs 47.6, 25.0% (3/12) and 13.4, 21.8% (17/78) vs 24.1, 12.2% (5/41); ≥ 3 ISTs (gMG only), 13.9, 50.0% (1/2) vs 0.0, 0.0% (0/2). One patient with gMG (2 ISTs) had meningococcal meningitis that resolved with antibiotics and eculizumab was resumed.
Conclusions
In AQP4+ NMOSD and AChR+ gMG, infection rates/100 PY were similar in eculizumab and placebo groups, regardless of concomitant IST. Infection rates/100 PY were consistent with the established safety profile of eculizumab.