Therapeutic thresholds for golimumab serum concentrations during induction and maintenance therapy in ulcerative colitis: results from the GO‐LEVEL study

Abstract

SummaryBackgroundSignificant associations between serum golimumab concentrations and favourable outcomes have been observed during both induction and maintenance therapy in ulcerative colitis (UC). However, data regarding optimal therapeutic serum golimumab concentration thresholds are limited.AimsTo identify optimal serum golimumab concentration thresholds during induction and maintenance treatment with golimumab.MethodsGO‐LEVEL was an open label, phase IV study that included a prospective cohort of UC patients commencing golimumab, as well as a cross‐sectional cohort receiving maintenance treatment. Patients commencing induction for active UC (defined as a simple clinical colitis activity index [SCCAI] >5 in addition to a raised faecal calprotectin [FC] >59μg/g or, raised C‐reactive protein [CRP] [>5mg/L] or, Mayo endoscopic disease activity 2 or 3) were evaluated at weeks 6, 10 and 14. Patients receiving maintenance therapy were recruited either at the point of flare or during remission. Combined clinical‐biochemical remission was defined as SCCAI ≤2 and FC <250μg/g. Serum golimumab concentrations were measured using a commercially available ELISA (LISATRACKER, Theradiag).ResultsThirty‐nine patients were included in the induction cohort, of whom 15 (38%) achieved combined clinical‐biochemical remission at week 6. The median serum golimumab concentration of those in combined clinical‐biochemical remission was significantly higher than those who were not (5.0 vs 3.1 μg/mL, respectively, P = 0.03). Receiver operating characteristic (ROC) curve analysis demonstrated 3.8 μg/mL as the optimal threshold (sensitivity 0.71, specificity 0.65, area under curve [AUC] 0.72, positive predictive value [PPV] 0.59 and negative predictive value [NPV] 0.79). Sixty‐three patients were included in the maintenance cohort; 31 (49%) were in combined remission, 32 (51%) were not. The median serum golimumab concentration of those in combined remission was significantly higher (2.9 vs 2.1 μg/mL, respectively, P = 0.01). ROC curve analysis demonstrated 2.4 μg/mL as the optimal threshold (sensitivity 0.68, specificity 0.66, AUC 0.68, PPV 0.65 and NPV 0.66).ConclusionsGO‐LEVEL (NCT03124121) offers further evidence regarding golimumab's exposure‐response relationship. Clinicians may consider using therapeutic drug monitoring to optimise golimumab dosing aiming to achieve our suggested therapeutic thresholds of 3.8 μg/mL at week 6 and 2.4 μg/mL during maintenance.

Predictors and Early Markers of Response to Biological Therapies in Inflammatory Bowel Diseases

“…The PANTS study, where anti-TNF naïve patients with luminal CD were enrolled at the time of anti-TNF initiation and prospectively observed until treatment discontinuation, reported that low TLs of infliximab (<7 mg/L) or adalimumab (<12 mg/L) at week 14 correlated with primary non-response at week 14 (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.20-0.62, p = 0.00038 for infliximab; OR 0.13, 95% CI 0.06-0.28, p < 0.0001 for adalimumab) and non-remission at week 54 (OR 0.29, 95% CI 0.16-0.52, p < 0.0001 for infliximab; OR 0.03, 95% CI 0.10-0.12, p < 0.0001 for adalimumab) [87]. Similar associations between TLs and therapeutic outcomes have also been observed for golimumab, both in the post-hoc analysis of the registration trial [88] and in some observational studies [89][90][91][92]. Some studies have suggested that specific disease phenotypes might need higher TLs to be adequately controlled.…”

Subcutaneous golimumab to treat a biological naïve chronically active ulcerative colitis child. A case report

“…Golimumab is also available in vials for infusion for very specific indications such as rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and active polyarticular juvenile idiopathic arthritis [ 14 ] Furthermore, clinical studies do not support the recommendation to treat low-weight children with 115/60 mg of golimumab. The GO-LEVEL study proposed using therapeutic drug monitoring to optimize golimumab dosing, with therapeutic thresholds of 3.8 g/mL at week 6 and 2.4 g/mL during maintenance [ 15 ]. This is also impractical, as these tests do not exist in many developing countries, including Syria.…”

Optimizing Therapies Using Therapeutic Drug Monitoring: Current Strategies and Future Perspectives

“…35 The evidence at the time was too sparse to recommend a cutoff for golimumab, although subsequent studies have reinforced a therapeutic level of 2.4 to 3.2 mg/mL during maintenance treatment. [36][37][38] These guidelines highlighted the many difficulties with recommending therapeutic cutoffs for biologics, as acknowledged by the authors and as further discussed below.…”