Effect of Intravenous Golimumab on Fatigue and the Relationship with Clinical Response in Adults with Active Ankylosing Spondylitis in the Phase 3 GO-ALIVE Study

Abstract

Introduction: We studied the effect of intravenous (IV)-golimumab on fatigue and the association of fatigue improvement with clinical response post hoc in adults with active ankylosing spondylitis (AS) in the GO-ALIVE trial.

Methods: Patients were randomized to IV-golimumab 2 mg/kg (N = 105) at week (W) 0, W4, then every 8 W (Q8W) or placebo (N = 103) at W0, W4, W12, crossover to IV-golimumab 2 mg/kg at W16, W20, then Q8W through W52. Fatigue measures included Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question #1 (fatigue; 0 [none], 10 [worst]; decrease indicates improvement) and 36-Item Short Form Health Survey (SF-36) vitality subscale (0 [worst], 100 [best]; increase indicates improvement). Minimum clinically important difference is ≥ 1 for BASDAI-fatigue and ≥ 5 for SF-36 vitality. GO-ALIVE primary endpoint was Assessment of SpondyloArthritis international Society ≥ 20% improvement criteria (ASAS20). Other clinical outcomes assessed included other ASAS responses, Ankylosing Spondylitis Disease Activity Score, and Bath Ankylosing Spondylitis Functional Index score. The distribution-based minimally important differences (MIDs) were determined for BASDAI-fatigue and SF-36 vitality. The relationship between improvement in fatigue and clinical outcomes was assessed via multivariable logistic regression.

Results: Mean changes in BASDAI-fatigue/SF-36 vitality scores were greater with IV-golimumab versus placebo at W16 (- 2.74/8.46 versus - 0.73/2.08, both nominal p ≤ 0.003); by W52 (after crossover), differences between groups narrowed (- 3.18/9.39 versus - 3.07/9.17). BASDAI-fatigue/SF-36 vitality MIDs were achieved by greater proportions of IV-golimumab-treated versus placebo-treated patients at W16 (75.2%/71.4% versus 42.7%/35.0%). A one-point/five-point improvement in BASDAI-fatigue/SF-36 vitality scores at W16 increased likelihood of achieving ASAS20 (odds ratios [95% confidence intervals]: 3.15 [2.21, 4.50] and 2.10 [1.62, 2.71], respectively) and ASAS40 (3.04 [2.15, 4.28] and 2.24 [1.68, 3.00], respectively) responses at W16; concurrent improvements and clinical response at W52 were consistent. A one-point/five-point improvement in BASDAI-fatigue/SF-36 vitality scores at W16 predicted increased likelihood of achieving ASAS20 (1.62 [1.35, 1.95] and 1.52 [1.25, 1.86], respectively) and ASAS40 (1.62 [1.37, 1.92] and 1.44 [1.20, 1.73], respectively) responses at W52.

Conclusions: IV-golimumab provided important and sustained fatigue improvement in patients with AS that positively associated with achieving clinical response.

Trial registration: ClinicalTrials.gov identifier, NCT02186873.

Keywords: Ankylosing spondylitis; Clinical response; Fatigue; Intravenous golimumab; Vitality.

Fig. 1

Mean (SD) change from baseline in the a BASDAI-fatigue score and the b SF-36 vitality score through week 52. Improvement is indicated by a decrease in BASDAI-fatigue score and increase in SF-36 vitality score. Patients randomized to placebo crossed over to IV-golimumab 2 mg/kg at week 16 (dotted line). Missing baseline data were replaced with the median value, and last observation carried forward was used for all other missing data. Nominal p values are based on analysis of covariance with factors of treatment group, baseline score, and prior TNFi therapy (Yes, No). BASDAI Bath Ankylosing Spondylitis Disease Activity Index, IV intravenous, SD standard deviation, SF-36 36-Item Short Form Health Survey, TNFi tumor necrosis factor inhibitor

Fig. 2

Proportion of patients who achieved a BASDAI-fatigue score (≥ 0.73) or b SF-36 vitality score (≥ 3.98) MID through week 52. Patients randomized to placebo crossed over to IV-golimumab 2 mg/kg at week 16 (dotted line). Missing baseline data were replaced with the median value, and last observation carried forward was used for all other missing data. Nominal p values are based on Cochran–Mantel–Haenszel test stratified by prior TNFi therapy (Yes, No). BASDAI Bath Ankylosing Spondylitis Disease Activity Index, IV intravenous, MID minimally important difference, SF-36 36-Item Short Form Health Survey, TNFi tumor necrosis factor inhibitor

Fig. 3

Proportion of patients who achieved an ASAS (a, c) or ASDAS response (b, d) at week 16 or 52 among patients randomized to IV-golimumab who did or did not achieve the BASDAI-fatigue score (≥ 0.73) or SF-36 vitality score (≥ 3.98) MID at week 16 or 52. Missing baseline data were replaced with the median value, and last observation carried forward was used for all other missing data. For week 52, nominal p values are based on a Cochran–Mantel–Haenszel test stratified by prior TNFi therapy (Yes, No). ASAS20 and ASAS40 are defined as ≥ 20% or ≥ 40% improvement, respectively, from baseline in ASAS criteria. ASAS 5/6 is defined as ≥ 20% improvement from baseline in any five of the six ASAS criteria. ASAS partial remission is defined as a score ≤ 2 out of ten in each of four ASAS domains (total back pain, patient’s global, function, and inflammation). ASDAS clinically important improvement and major improvement are defined as a decrease ≥ 1.1 or decrease ≥ 2.0, respectively, in ASDAS. ASDAS inactive disease is defined as an ASDAS score < 1.3. ASAS Assessment of SpondyloArthritis international Society, ASDAS Ankylosing Spondylitis Disease Activity Score, BASDAI Bath Ankylosing Spondylitis Disease Activity Index, IV intravenous, MID minimally important difference, SF-36 36-Item Short Form Health Survey, TNFi tumor necrosis factor inhibitor