Maxime Verhoeven

80 Chapter 5 ABSTRACT Objective To compare the effect of preventing radiographic progression (in its 3 components) of tocilizumab (TCZ) monotherapy with those of TCZ combined with methotrexate (TCZ+MTX), and to evaluate possible effect modifiers. Methods Randomized trials comparing TCZ-monotherapy with TCZ+MTX combination therapy regarding radiographic progression were analyzed on individual patient (n=820) data level for early as well as established RA patients using mixed-effects models. Outcomes were: not having radiographic progression after 2 years (i.e., preventing radiographic progression), respectively in total Sharp van der Heijde (SvdH) score, in erosion score and in joint space narrowing (JSN) score. Effect modification by baseline joint damage, disease duration and DAS28 was studied. Results Overall, TCZ+MTX was more effective in preventing radiographic progression regarding total SvdH scores compared to TCZ-monotherapy. However, in early RA patients with more joint damage (RR 1.02 vs. 0.91 for the less damage group), or a lower DAS28 (RR 1.04 vs. 0.92) at baseline, this advantage disappeared. In established RA, the advantage of TCZ+MTX over TCZ in preventing radiographic progression disappeared with a longer disease duration at baseline (RR 1.04 vs. 0.83). Results for erosion scores as outcome were in line, but were less clear for JSN. Conclusion Combination therapy with TCZ+MTX is more effective in preventing radiographic progression compared to TCZ-monotherapy, but the effectiveness of TCZ-monotherapy may approximate the effectiveness of TCZ+MTX in early RA patients with more joint damage and/or a lower DAS28 at baseline, and in established RA patients with longer disease duration.