Appendix 4Additional figures and tables

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TABLE 8

TABLE 8

Follow-up rates for sMMSE and BADLS by treatment arm and time point

TABLE 9

TABLE 9

Skin toxicity incidence and severity by treatment arm

TABLE 10

TABLE 10

Causes of death

FIGURE 7. Proportion of participants taking trial treatment over time: Kaplan–Meier plot.

FIGURE 7

Proportion of participants taking trial treatment over time: Kaplan–Meier plot.

FIGURE 8. Flow chart showing the completeness over time of participant follow-up.

FIGURE 8

Flow chart showing the completeness over time of participant follow-up. Colour coding to show assessments split by treatment arm: navy font is 400 mg of minocycline, light blue font is 200 mg of minocycline and red font is placebo.

FIGURE 9. Change in sMMSE and BADLS scores from baseline to month 24 using imputation methods 1 (a and b) and 2 (c and d).
FIGURE 9. Change in sMMSE and BADLS scores from baseline to month 24 using imputation methods 1 (a and b) and 2 (c and d).
FIGURE 9. Change in sMMSE and BADLS scores from baseline to month 24 using imputation methods 1 (a and b) and 2 (c and d).
FIGURE 9. Change in sMMSE and BADLS scores from baseline to month 24 using imputation methods 1 (a and b) and 2 (c and d).

FIGURE 9

Change in sMMSE and BADLS scores from baseline to month 24 using imputation methods 1 (a and b) and 2 (c and d). A to estimate scores for patients with no follow-up past baseline. Graph shows change in mean sMMSE and BADLS scores with standard errors. Baseline scores are set to zero and p-values are from tests for time-by-treatment interaction from repeated measures analyses. (a) Average change in sMMSE score from baseline to month 24, using imputation (baseline scores are 26.3 points for 400 mg of minocycline, 26.5 points for 200 mg of minocycline and 26.4 points for placebo). (b) Average change in BADLS score from baseline to month 24, using imputation (baseline scores are 5.6 points for 400 mg of minocycline, 4.9 points for 200 mg of minocycline and 5.5 points for placebo). (c) Average change in sMMSE score from baseline to month 24 using imputation. (d) Average change in BADLS score from baseline to month 24, using imputation.

FIGURE 10. Subgroup analyses of change in sMMSE score over 24 months for minocycline (any dose) vs.

FIGURE 10

Subgroup analyses of change in sMMSE score over 24 months for minocycline (any dose) vs. placebo by baseline characteristics: duration of symptoms, baseline sMMSE score, age and gender. Results are derived from a repeated measures model, with p-values from tests for interaction between treatment and the selected subgroup. Min., minimum. The p-value is from the test statistic for testing the interaction between the treatment and any subgroup variable.

FIGURE 11. Probability of (a) overall survival, (b) institutionalisation and (c) time to death or institutionalisation by treatment arm: Kaplan–Meier survival plots.
FIGURE 11. Probability of (a) overall survival, (b) institutionalisation and (c) time to death or institutionalisation by treatment arm: Kaplan–Meier survival plots.
FIGURE 11. Probability of (a) overall survival, (b) institutionalisation and (c) time to death or institutionalisation by treatment arm: Kaplan–Meier survival plots.

FIGURE 11

Probability of (a) overall survival, (b) institutionalisation and (c) time to death or institutionalisation by treatment arm: Kaplan–Meier survival plots.

FIGURE 12. Average decline of sMMSE score split by baseline sMMSE score (i.

FIGURE 12

Average decline of sMMSE score split by baseline sMMSE score (i.e. a score of 24–26 or 27–30a points). a, Eight patients start with a sMMSE score of 30 points and have a 24-month sMMSE score of 30 points.

TABLE 11

TABLE 11

Line-by-line listings of categorised SAEs