Polymyalgia rheumatic
Table 1 Demographic and disease characteristics of patients at baseline*
Tocilizumab N=19
Placebo N=17
Characteristic
Age (years) Female sex
68.8±9.0
71.1±9.0
52.6% 100%
52.9% 100%
Caucasian ethnicity
Weight (kg)
81.7±28.5 26.5±4.5
72.0±13.9 25.7±3.9
Body mass index (kg/m 2 ) Disease duration (days) at screening Patients on prednisone Current prednisone dose (mg) Erythrocyte sedimentation rate (mm/hour) C-reactive protein (mg/dL)
8±5
6±3
100%
94%
16.7±3.9 24.3±16.4
17.2±3.1 24.1±18.7
1.6±2.4
0.98±1.5 22.8±16.7 26.0±24.4
Pain by Visual Analogue Scale (mm) 30.8±26.0
Patient global assessment of disease activity by Visual Analogue Scale (mm) Heath Assessment Questionnaire (0–3) Short Form-36 physical component score (0–100)
30.1±25.9
0.64±0.60
0.65±0.61
47.7±7.5
45.9±5.2
*Data shown are means±SD, unless stated otherwise.
and 935 mg (IQR 861–1244) in the placebo group (p=0.003); over 24 weeks it was 781mg (IQR 721–972) and 1290mg (IQR 1106–1809), respectively (p=0.001; online supplemental figure 1). In figure 2C, the mean doses are shown which are more sensitive to depict dose increases of individual patients over time (no statistical analysis done). No significant difference was observed for proportions of patients with increased CRP or ESR at week 24 (table 2), all subsequent outcomes were not formally tested statistically. However, exploratory statistical analysis on secondary outcomes revealed no difference between the two groups (online supplemental table 2). At week 24, median CRP levels in the tocilizumab and placebo groups were 0.28 (IQR 0.09–1.07) and 0.71 (IQR 0.30–2.01) mg/dL, respectively (p=0.15); and median ESR levels were 12 (IQR 11–35) and 12 (IQR 6–20) mm/hour (p=0.12; online supplemental table 3). Safety The total number of adverse events per 100 patient-years was 490.6 (468.9–523.2) in the tocilizumab group and 555.0 (531.9–579.0) in the placebo group (table 3). In 41% of patients in the placebo group, clinical musculoskeletal adverse events were recorded, which had not been adjudicated as flare by the respective investigators. The most frequent adverse events were infections, which occurred in 63% of patients in the tocili- zumab group and 35% in the placebo group, none of them were serious (online supplemental table 4). None of the patient of the tocilizumab or the placebo group held treatment. One patient in the tocilizumab group and five patients in the placebo group developed serious adverse events. None of the patients in the tocilizumab group and two patients in the placebo group withdrew due to serious adverse events: one had pancreatitis and one a duodenal ulcer. In the placebo group, one patient was withdrawn because of a dental abscess and one developed seronegative rheumatoid arthritis. No gastrointestinal perfora- tions, anaphylaxis, myocardial infarctions or malignancies were reported. There were no deaths during the trial period.
Sensitivity analyses To confirm robustness of the results, we performed two sensi- tivity analyses: first, we performed a per-protocol evaluation of the primary outcome (instead of the intent-to-treat anal- ysis) to address the impact of the observed imbalance in drop outs between the two study arms on the results: 12/17 (70.6%) patients achieved glucocorticoid-free remission at week 16 in the tocilizumab group and 2/12 (16.7%) in placebo group (p=0.004), the corresponding OR for tocilizumab versus placebo was 13.5 (2.0–90.7). Second, we performed a post-hoc analysis, in which we included information on CRP and ESR in addition to the clinical evaluation of remission, since the study design had required blinding of investigators to these measures, and could therefore not be part of the remission assessment: if normal CRP and ESR would have been required for remission, none of the patients in the placebo group would have achieved glucocorticoid-free remission at week 16, whereas the number of patients in remission remained the same in the tocilizumab group 12/19 (63.2%), where all patients had suppressed CRP/ Figure 2 Efficacy analysis for patients treated with tocilizumab or placebo. ( A) Glucocorticoid-free remission at weeks 12, 16 (primary endpoint; p=0.002) and 24. (B) Time to relapse (Kaplan-Meier curves censoring patients who dropped out or were lost to follow-up). (C) Mean cumulative prednisone dose over time.
Bonelli M, et al . Ann Rheum Dis 2022; 81 :838–844. doi:10.1136/annrheumdis-2021-221126
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