While ruling out opportunistic infection, it can also be very important to assess for inflammation as well as drug levels of the medications currently used in treatment. Drug levels paired with inflammatory markers can give important information as to what is causing the current issue with suspected nonresponse.

When beginning the initial laboratory assessment, objective data such with CRP and fecal biomarkers have proven valuable when evaluating for inflammation. The two currently commercially available fecal biomarkers are stool calprotectin and lactoferrin. Fecal biomarkers are helpful as an adjunctive management tool in those with inflammatory disease to monitor disease activity and predict relapse [9]. Obtaining one or both of these biomarkers at significant waypoints in treatment, such diagnosis or treatment onset can provide valuable information. Once inflammatory results are obtained, they can be paired with drug levels giving us valuable insight into disease activity, medication dosing, and even compliance. Superimposing the above data upon clinical suspicion and if needed radiologic and/or endoscopic testing is necessary when making the decision of medication failure or nonresponse.

When treating with TNF-alpha agents, it’s important to realize and correctly identify lack or loss of response to anti-TNF agents thereby avoiding complication of inadequately treated disease. To begin a causal investigation, we must first identify if inflammation is present before increasing, changing or checking levels of medication. Once completed this will allow placement of the patient into one of three categories—(1) low drug level, (2) adequate drug level and increased inflammatory biomarkers, and (3) adequate drug level and normal biomarkers (Table 13.1).

Those patients with low drug level must first be evaluated for compliance. Other causes of low levels may include high inflammatory disease burden or clearance of drug due to antidrug antibodies (ADAs). It may be important to check serum for ADAs at this time to aid in treatment decisions.

If it’s discovered that the patient has adequate drug level and high inflammatory biomarkers, this may be indicative of an inflammatory shift of the disease to a non-TNF-alpha pathway. It may also indicate another disease process such as infection, vasculitis, or ischemia.

Lastly are those patients with normal biomarkers and adequate drug level. Patients may have one of the many causes of noninflammatory-related complications of Crohn’s disease including a fibrostenotic stricture, IBS, neoplasm, choleretic diarrhea, SIBO, or even amyloid deposition.

Based on the proposed categories, we should have a fairly accurate idea of which category our patient may fit. Based on these data, further diagnostic work-up may be selected. This may include ileocolonoscopy, CT/MRI-based studies, or wireless capsule endoscopy. Capsule endoscopy has been shown superior to all other modalities for diagnosing non-stricturing small bowel CD [10]. One important note to remember is that a capsule can be retained if a stricture is present. Employing an Agile (brand name) patency capsule prior to deploying the video capsule could prove beneficial to prevent capsule retention [11].

Remember, the first step to treating loss of response is prevention. This is done by avoiding episodic therapy and ensuring adequate drug levels. This will avoid subtherapeutic drug levels and minimize antibody formation [12].

If the patient is in fact experiencing loss of response, options include the addition of an immunomodulator, dose escalation of their current TNF therapy, or changing to a different therapy of the same or different mechanism of action.