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What you might not know about anti-TNF monitoring…
January 11, 2014 9:00 am
At a recent group dinner meeting, we had the opportunity to review therapeutic anti-TNF monitoring. In addition, we discussed emerging treatments for inflammatory bowel disease, like golimumab, tofacintinib and vedolizumab.
As noted in previous blog entries (see below), therapeutic anti-TNF monitoring can help adjust treatment. Namely, if a patient loses response to therapy and has low trough levels of anti-TNF (Infliximab ❤ μg/mL, Adalimumab <8 μg/mL, or certolizumab <27.5 μg/mL) without antidrug antibodies (ADAs), then increasing the dose is likely to be effective. However, if a patient has a therapeutic level and is not responding, changing to another agent and/or further investigation is worthwhile.
So, what information is new?
- Only about 20% of patients who lose clinical response develop ADAs. So, drug level, rather than ADAs, is most helpful.
- For infliximab, adjusting dose 14 weeks into therapy to achieve a target trough level between 3-7 mcg/mL may be helpful.
- Severe colitis patients may need higher initial doses (?as high as 20 mg/kg) due to potential for ‘antigen sink.’ This is due to notably higher clearance in the presence of low albumin, and high CRP. Other factors that increase clearance include higher BMI and male gender.
- About 1/2 of patients who receive higher doses due to severe disease may be able to deescalate dosage when improved. (?which half)
- Currently, a reactive approach to checking levels is common in U.S. in part due to costs associated with checking trough levels and ADAs (as much as $2500). That is, most commonly checking levels is undertaken in patients with suboptimal clinical response. A proactive approach to achieve target levels may be shown to be helpful.
- While studies have not shown higher adverse reactions with higher trough levels, there are a few clinical situations in which lower trough levels can be important. In patients with psoriatic skin lesions and arthralgias, if trough levels are elevated, lowering the dose may be helpful.
Outstanding questions?
- Should patients have drug levels checked when they are asymptomatic?
- How does a practitioner account for variability among different laboratory assays?
- What is the optimal target level for each anti-TNF agent? Is this different in Crohn disease compared with ulcerative colitis? Is the trough target level different in adults than children?
- Is there a toxic level?
- If a rapid test response were available, would checking drug levels be needed for hospitalized patients to assess anti-TNF rescue therapy?
Related blog links:
Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition
Posted by gutsandgrowth
Categories: Pediatric Gastroenterology Intestinal Disorder
Tags: adalimumab, antibodies to infliximab, antidrug antibodies, certolizumab, crohn disease, infliximab, tofacitinib, Ulcerative colitis, Vedolizumab
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Another question. When can you simply add an adjuvant like MTX instead of burning a drug and switching. That addition is always my preference and often works.
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