Table 1.
Clinical trials used for weighted regression analysis.
| Index | Trial | Year | Experimental arm | Control arm | n | Trial duration (years) | Weight | Age at baseline (years) | IDP (%) |
p-Value | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Raw | Recalculated | ||||||||||
| A1 | CAMMS223 | 2008 | Alemtuzumab | Interferon beta-1a (Rebif) | 223 | 3.00 | 386.25 | 32.35 | 58.00 | 73.69 | 0.005 |
| A2 | CARE-MS I | 2012 | Alemtuzumab | Interferon beta-1a (Rebif) | 563 | 2.00 | 796.20 | 33.07 | 30.00 | 55.12 | 0.220 |
| A3 | CARE-MS II | 2012 | Alemtuzumab | Interferon beta-1a (Rebif) | 628 | 2.00 | 888.13 | 35.12 | 42.00 | 60.39 | 0.008 |
| D1 | SELECT | 2013 | Daclizumab HYP | Placebo | 397 | 1.00 | 397.00 | 35.94 | 57.00 | 57.00 | 0.021 |
| D2 | DECIDE | 2015 | Daclizumab HYP | Interferon beta-1a (Avonex) | 1841 | 2.76 | 3,059.41 | 36.30 | 16.00 | 40.63 | 0.160 |
| DF1 | CONFIRM | 2012 | Dimethyl fumarate | Placebo | 541 | 1.84 | 733.39 | 37.50 | 21.00 | 21.00 | 0.250 |
| DF2 | DEFINE | 2012 | Dimethyl fumarate | Placebo | 817 | 1.84 | 1,108.56 | 38.30 | 38.00 | 38.00 | 0.005 |
| F1 | FREEDOMS | 2010 | Fingolimod | Placebo | 843 | 2.00 | 1,192.18 | 36.90 | 30.00 | 30.00 | 0.020 |
| F2 | FREEDOMS II | 2014 | Fingolimod | Placebo | 713 | 1.97 | 1,001.06 | 40.35 | 17.00 | 17.00 | 0.227 |
| F3 | INFORMS | 2016 | Fingolimod | Placebo | 823 | 4.32 | 1,709.60 | 48.50 | 11.99 | 11.99 | 0.217 |
| F4 | TRANSFORMS | 2010 | Fingolimod | Interferon beta-1a (Avonex) | 860 | 1.00 | 860.00 | 36.35 | 25.32 | 47.14 | 0.250 |
| G1 | Copolymer 1 MS Study Group | 1995 | Glatiramer acetate | Placebo | 251 | 2.00 | 354.97 | 34.45 | 12.20 | 12.20 | NS |
| G2 | PROMiSe | 2007 | Glatiramer acetate | Placebo | 935 | 3.00 | 1,619.47 | 50.40 | 13.00 | 13.00 | 0.175 |
| G3 | REGARD | 2008 | Glatiramer acetate | Interferon beta-1a (Rebif) | 764 | 1.84 | 1,036.65 | 36.75 | 25.64 | 46.76 | 0.117 |
| G4 | BEYOND | 2009 | Glatiramer acetate | Interferon beta-1b (Betaseron) | 1343 | 2.00 | 1,899.29 | 35.60 | 4.76 | 34.04 | 0.680 |
| G5 | CONFIRM | 2012 | Glatiramer acetate | Placebo | 532 | 1.84 | 721.18 | 37.34 | 7.00 | 7.00 | 0.700 |
| G6 | CombiRx | 2013 | Glatiramer acetate | Interferon beta-1a (Avonex) | 487 | 3.00 | 843.51 | 38.31 | −14.92 | 14.08 | Not given |
| I1 | MSCRG | 1996 | Interferon beta-1a (Avonex) | Placebo | 301 | 2.00 | 425.68 | 36.80 | 37.25 | 37.25 | 0.020 |
| I2 | Montalban et al. | 2009 | Interferon beta-1b (Betaseron) | Placebo | 73 | 2.00 | 103.24 | 48.70 | 20.83 | 20.83 | 0.314 |
| I3 | Leary SM et al. | 2003 | Interferon beta-1a (Avonex) | Placebo | 35 | 2.00 | 49.50 | 44.50 | −20.00 | −20.00 | NS |
| I4 | PRISMS | 1998 | Interferon beta-1a (Rebif) | Placebo | 283 | 2.00 | 399.52 | 34.90 | 17.76 | 17.76 | <0.05 |
| I5 | PRISMS | 1998 | Interferon beta-1a (Rebif) | Placebo | 278 | 2.00 | 392.44 | 34.90 | 28.73 | 28.73 | <0.05 |
| I6 | SPECTRIMS | 2001 | Interferon beta-1a (Rebif) | Placebo | 259 | 3.00 | 447.74 | 42.97 | 12.00 | 12.00 | 0.305 |
| I7 | SPECTRIMS | 2001 | Interferon beta-1a (Rebif) | Placebo | 248 | 3.00 | 428.68 | 42.63 | 17.00 | 17.00 | 0.146 |
| I8 | INFB MS Study Group | 1995 | Interferon beta-1b (Betaseron) | Placebo | 244 | 5.00 | 545.60 | 35.50 | 23.21 | 23.21 | 0.096 |
| I9 | EUSPMS | 1998 | Interferon beta-1b (Betaseron) | Placebo | 718 | 2.75 | 1,190.67 | 41.00 | 21.73 | 21.73 | 0.005 |
| I10 | NASPMS | 2004 | Interferon beta-1b (Betaseron) | Placebo | 625 | 3.00 | 1,082.53 | 46.80 | 5.59 | 5.59 | 0.590 |
| I11 | ADVANCE | 2014 | Pegylated interferon beta-1a (Plegridy) | Placebo | 1012 | 0.92 | 970.96 | 36.60 | 38.00 | 38.00 | 0.038 |
| I12 | BRAVO | 2014 | Interferon beta-1a (Avonex) | Placebo | 672 | 2.00 | 950.35 | 38.00 | 26.00 | 26.00 | 0.130 |
| L1 | ALLEGRO | 2012 | Laquinimod | Placebo | 1106 | 2.00 | 1,564.12 | 38.70 | 36.00 | 36.00 | 0.010 |
| L2 | BRAVO | 2014 | Laquinimod | Placebo | 659 | 2.00 | 931.97 | 37.10 | 31.00 | 31.00 | 0.063 |
| M1 | MIMS | 2002 | Mitoxantrone | Placebo | 124 | 2.00 | 175.36 | 39.98 | 63.64 | 63.64 | 0.036 |
| N1 | AFFIRM | 2006 | Natalizumab | Placebo | 942 | 2.30 | 1,429.04 | 36.00 | 54.00 | 54.00 | <0.001 |
| N2 | SENTINEL | 2006 | Natalizumab + IFN-beta-1a (Avonex) | IFN-beta-1a (Avonex) + Placebo | 1171 | 2.30 | 1,776.44 | 38.90 | 24.00 | 24.00 | 0.020 |
| N3 | ASCEND | 2016a | Natalizumab | Placebo | 887 | 1.84 | 1,203.54 | 47.20 | −6.67 | −6.67 | 0.753 |
| O1 | OPERA I | 2016 | Ocrelizumab | Interferon beta-1a (Rebif) | 821 | 1.84 | 1,113.99 | 37.00 | 43.00 | 58.90 | 0.010 |
| O2 | OPERA II | 2016 | Ocrelizumab | Interferon beta-1a (Rebif) | 835 | 1.84 | 1,132.99 | 37.30 | 37.00 | 54.19 | 0.020 |
| O3 | ORATORIO | 2016 | Ocrelizumab | Placebo | 731 | 2.85 | 1,234.07 | 44.60 | 25.00 | 25.00 | 0.040 |
| R1 | OLYMPUS | 2009 | Rituximab | Placebo | 439 | 1.84 | 595.67 | 49.90 | 23.00 | 23.00 | 0.144 |
| S1 | EXPAND | 2016a | Siponimod | Placebo | 1363 | 1.75 | 1,803.08 | 48.00 | 21.00 | 21.00 | 0.013 |
| T1 | TEMSO | 2011 | Teriflunomide | Placebo | 547 | 2.07 | 786.51 | 37.73 | 23.70 | 23.70 | 0.080 |
| T2 | TEMSO | 2011 | Teriflunomide | Placebo | 540 | 2.07 | 776.44 | 38.00 | 29.80 | 29.80 | 0.030 |
| T3 | TOWER | 2014 | Teriflunomide | Placebo | 601 | 1.54 | 746.87 | 37.63 | 5.00 | 5.00 | 0.762 |
| T4 | TOWER | 2014 | Teriflunomide | Placebo | 564 | 1.60 | 714.14 | 38.17 | 32.00 | 32.00 | 0.044 |
Of the 44 clinical trials analyzed, 6 of these trials were conducted using two treatments arms and one control arm to give 38 independent trials. For the weighted regressions, each arm was considered as an independent trial, and patients in the control arms were divided equally between the treatment arms. Age at baseline was calculated by adding the products of mean age and sample size for each group (experimental and control) and then dividing by the total sample size. The raw value for percent inhibition of disability progression (%IDP) was calculated using Eq. 1 in Section “Materials and Methods” and then recalculated (for trials with interferon beta as active comparator) using Eq. 7. The p-value denotes the significance of the reported difference in confirmed disability progression between trials arms. For trials that did not report a p-value (due to non-significant results), these p-values are denoted by NS. A complete table with trial references, doses, and calculations can be found in the uploaded Excel file in Supplementary Material.
aUnpublished Trial.