Therapeutic drug monitoring (TDM) doesn’t appear to improve clinical outcomes in patients starting infliximab therapy, a European study suggests.
The Norwegian Drug Monitoring Trial (NOR-DRUM) is believed to be the first RCT to compare TDM versus a standard approach to dosing in patients with any approved indication for infliximab.
Part A of the study randomised 411 adults with either Crohn’s disease, ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, spondyloarthritis or psoriasis.
Patients in the TDM arm had their serum drug levels measured before every infusion and their infliximab dose and infusion interval adjusted in order to reach the therapeutic range.
Dr Silje Syversen, a researcher and rheumatology consultant at Diakonhjemmet Hospital, told the ACR 2020 Virtual Meeting that TDM did not improve clinical remission rates or any other efficacy outcomes at 30 weeks.
Clinical remission overall was 53% with TDM compared to 54% with a standard approach to dosing (p=0.78).
The finding that TDM was not superior to standard administration of infliximab was consistent across all six disease sub-groups.
Dr Syversen said the number of adverse events was also similar in both groups.
‘But infusion reactions which are often related to low drug levels and the development of anti-drug antibodies were less frequent in patients receiving TDM (2.5% v 8.0%).”
“This study shows that TDM during induction of infliximab is not superior to standard treatment,” she concluded.
“Although the study indicated improved safety by a reduction in infusion reactions, implementation of TDM as a general strategy in the induction period of infliximab is not supported by the NOR-DRUM.”
She said TDM was an issue of long-standing debate.
“Despite a lack of clinical trials data and diverging guidelines, TDM has already been adopted in clinical practice.”
She said the study showed that as with drugs, monitoring tools and treatment strategies should be tested in clinical trials before implementation.
Commenting on the findings, Dr David Liew a Melbourne rheumatologist and clinical pharmacologist, told the limbic it was perhaps surprising that TDM failed to be effective across all the disease groups.
“In rheumatology we haven’t been using it [TDM] and my colleagues have resisted it because they didn’t feel that there was a need, whereas in inflammatory bowel disease TDM is used quite frequently and Australia has led the way in some ways in trying to standardise dose optimisation with TDM.”
He said the NOR-DRUM investigators were now motivated to see whether some other patient subgroups might benefit.
“We know that some patients might benefit more than others. So it might be about drilling down into which high risk patients might actually benefit from early dose optimisation.”
“But I think it’s later on – maybe not in that initial induction phase but in the maintenance phase where we can try to modify the dose especially if immunogenicity comes into play where TNF inhibitor TDM has always been strongest.”
Part B of the NOR-DRUM study is underway to assess the effectiveness of TDM in the maintenance phase of infliximab therapy.
Dr Liew added that the TDM story also doesn’t stop at TNF inhibitors with early work on rituximab drug levels also presented at ACR Convergence 2020.