Table 2.
Efficacy End Points (Intention-to-Treat and Per-Protocol Populations).*
| Variable | Transplantation | Cyclophosphamide | P Value† |
|---|---|---|---|
| Intention-to-treat population | |||
| No. of participants | 36 | 39 | |
| Primary efficacy end point: GRCS at 54 mo‡ | |||
| Median (range) | 17.0 (−58 to 52) | −6.0 (−58 to 52) | 0.01 |
| Percent of favorable pairwise comparisons | 66.6 | 33.4 | |
| GRCS at 48 mo‡ | |||
| Median (range) | 20.0 (−58 to 55) | −8.0 (−58 to 55) | 0.008 |
| Percent of favorable pairwise comparisons | 67.6 | 32.4 | |
| Death or respiratory, renal, or cardiac failure — no. (%) | |||
| By 54 mo | 10 (28) | 20 (51) | 0.06 |
| By 48 mo | 10 (28) | 20 (51) | 0.06 |
| Death from any cause — no. (%) | |||
| By 54 mo | 6 (17) | 11 (28) | 0.28 |
| By 48 mo | 6 (17) | 11 (28) | 0.28 |
| Treatment-related death — no. (%)§ | |||
| By 54 mo | 1 (3) | 0 | 0.48 |
| By 48 mo | 1 (3) | 0 | 0.48 |
| Per-protocol population | |||
| No. of participants | 33 | 34 | |
| GRCS at 54 mo‡ | |||
| Median (range) | 16.0 (−56 to 46) | −11.0 (−56 to 46) | 0.004 |
| Percent of favorable pairwise comparisons | 70.1 | 29.9 | |
| GRCS at 48 mo‡ | |||
| Median (range) | 17 (−56 to 49) | −13.0 (−56 to 49) | 0.003 |
| Percent of favorable pairwise comparisons | 71.3 | 28.7 | |
| Death or respiratory, renal, or cardiac failure — no. (%) | |||
| By 54 mo | 7 (21) | 17 (50) | 0.02 |
| By 48 mo | 7 (21) | 17 (50) | 0.02 |
| Death from any cause — no. (%) | |||
| By 54 mo | 3 (9) | 8 (24) | 0.19 |
| By 48 mo | 3 (9) | 8 (24) | 0.19 |
| Treatment-related death — no. (%)§ | |||
| By 54 mo | 1 (3) | 0 | 0.49 |
| By 48 mo | 1 (3) | 0 | 0.49 |
| Disease-progression event by 54 mo — no. (%) | |||
| Initiated DMARDs¶ | 3 (9) | 15 (44) | 0.001 |
| New or worsening arrhythmia | 6 (18) | 4 (12) | 0.46 |
| Congestive heart failure leading to treatment | 0 | 4 (12) | 0.04 |
| Clinically significant pericardial effusion | 2 (6) | 0 | 0.15 |
| Pulmonary arterial hypertension | 0 | 5 (15) | 0.02 |
| Scleroderma-related renal crisis | 0 | 1 (3) | 0.32 |
| Myositis | 1 (3) | 0 | 0.31 |
The intention-to-treat population was defined as all the participants who had undergone randomization. The per-protocol population was defined as participants who received a transplant or completed nine or more doses of cyclophosphamide. Because pulmonary and renal toxic effects are expected and reversible during the recovery period after autologous stem-cell transplantation, events of respiratory failure or renal failure were not evaluated in either treatment group until month 14 and month 8, respectively.
For the global rank composite score (GRCS), P values are based on the Wilcoxon signed-rank test. For death with or without respiratory, renal, or cardiac failure, P values are based on Fisher’s exact test. For disease-progression events by 54 months, P values are based on Pearson’s chi-square test.
The range for the GRCS is sample specific and depends on the number of participants included in the analysis and the number of ties in score. The higher the score, the better the participant’s performance relative to others in the sample. Percent refers to the percent of pairwise comparisons between participants that favored transplantation or cyclophosphamide. For example, in the intention-to-treat analysis at 54 months, with 36 participants in the transplantation group and 39 in the cyclophosphamide group, there were 1404 possible pairwise comparisons (i.e., 36 × 39). In 935 of the 1404 paired comparisons (66.6%), the global rank composite score favored transplantation.
“Related” includes events that were deemed to be probably or definitely related to the treatment regimen or CD34+ hematopoietic progenitor cells, as reported by the site investigator. By 72 months, there were 2 deaths (6%) in the transplantation group and 0 in the cyclophosphamide group (intention-to-treat and per-protocol populations).
By 24 months, a total of three participants (9%) in the transplantation group and seven participants (21%) in the cyclophosphamide group had initiated disease-modifying antirheumatic drugs (DMARDs).