Feature

Therapeutic Drug Monitoring in Rheumatology: A Promising Outlook But Many Barriers to Overcome


 

Who May Benefit Most From TDM?

In the NOR-DRUM trials, patients at risk of developing ADA early on, before a disease flare or infusion reaction, seemed to benefit most from TDM. But who are those patients?

“We looked at risk factors for developing antidrug antibodies, and we found that patients with high disease activity when starting treatment, smokers, and patients with rheumatoid arthritis had a higher risk than other patients, as did patients who are not using concomitant immunosuppressive therapy,” Brun said.

“During treatment, we also found that low serum drug levels and drug holidays above 11 weeks were also risk factors,” she added.

The NOR-DRUM researchers also evaluated genetic risk factors and found that patients with the HLA-DQ2 gene variant were also at increased risk of developing ADA.

While NOR-DRUM evaluated only infliximab, some of its lessons may be applied to other DMARDs, Brun said. “We think that for other subcutaneously administered TNF inhibitors, you would probably see the same effect of proactive TDM, but we currently do not have data on that,” she said. A study similar to the NOR-DRUM design will evaluate this in Norway, Brun added.

She explained why the findings with infliximab may extend to adalimumab, which may be the second most immunogenic TNF inhibitor after infliximab. “The administration is different; it’s administered more often than infliximab; that would also make the results more uncertain to generalize to the other treatments, but I would guess there are also benefits of using TDM in other treatments.”

Potential Risks for TDM

Wallace has noted that TDM, with the current state of evidence, carries a number of potential risks. “The potential risks might be that you unnecessarily discontinue a medication because you detected an antibody, or the level seems low and you’re not able to get it higher, but the patient is otherwise doing fine,” he said. “You might end up increasing doses of the medicine that would put the patient at potentially increased risk of infection, as well as obviously more costs.”

That would also lead to more utilization of resources and costs, he said. “Some of those reasons are why there has been hesitation with therapeutic drug monitoring,” Wallace added.

A number of questions also surround the use of biosimilars and ADA levels, Wallace said. While a review of clinical trials found no meaningful differences in terms of immunogenicity between biosimilars and reference products, it did note discrepancies in how the agents were evaluated.

What DMARDs Are Most Suitable for TDM?

Petri said TDM would be useful for monitoring patients on mycophenolate mofetil. “A trough level can at least tell us if a patient is taking it,” she said. “Tacrolimus, used for lupus nephritis, has well-accepted peak and trough trends due to widespread use in transplant.”

Drugs with a wide variability in pharmacokinetics may also be suitable for TDM, Balevic said. That would include hydroxychloroquine, azathioprine, mycophenolate, or even cyclophosphamide. Drugs that have a narrow therapeutic index, such as tacrolimus, cyclosporine, or again, cyclophosphamide, might also be amenable to TDM, he said.

Pages

Recommended Reading

Kidney Disease May Accelerate With Higher Rheumatoid Arthritis Disease Activity
MDedge Rheumatology
Diets Higher in Ultra-Processed Foods Raise Risk for Rheumatoid Arthritis
MDedge Rheumatology
Early Use of Steroids Linked to Prolonged Treatment in Early Rheumatoid Arthritis
MDedge Rheumatology
Rheumatology Clinic Interventions for Smoking, Blood Pressure ‘Make a Big Difference’
MDedge Rheumatology
Direct-to-Consumer Testing’s Expansion to Rheumatology Has Benefits but Potential Risks
MDedge Rheumatology
ILD Subtypes in Rheumatoid Arthritis Carry Different Risk Factor Profiles
MDedge Rheumatology
Methotrexate in Preventing RA: Benefits in ACPA-Negative Patients, and Is It Cost Effective?
MDedge Rheumatology
New Scanner Creates Highly Detailed, 3D Images of Blood Vessels in Seconds
MDedge Rheumatology
Too Few Immunocompromised Veterans Are Getting Zoster Vaccinations
MDedge Rheumatology
Few Differences Seen in RA Pain Outcomes for JAK Inhibitors, Biologics
MDedge Rheumatology