A recent review article (Feuerstein JD et al. Inflamm Bowel Dis 2015; 21: 1176-86) serves as a useful reference regarding immune-mediated reactions to anti-tumor necrosis factor (anti-TNF) medications used in inflammatory bowel disease (IBD).

Background:

• All anti-TNF agents induce antidrug antibodies (ADAs).
• With regard to infliximab (IFX) which has the most literature, it is well-recognized that combination therapy with an immunomodulator reduces the risk of antibodies to infliximab (ATIs).  For example, in the SONIC study, ATIs were noted in 0.9% of those with combination therapy compared with 14.6% of those receiving monotherapy with IFX.  With the UC-SUCCESS, the rates were 19% and 3% respectively.

Acute Infusion Reactions -Key points:

• Acute infusion reactions (IRs) are more common in patients with ADAs.  IRs can be categorized as acute (w/in 24h) and chronic (2-14 d after infusion).
• Acute IRs can be mild (dizziness, flushing, nausea, palpitation), moderate (chest pain, hypertension [SBP increase of more than 20], hypotension, fevers urticaria, mild dyspnea, chills, rash) or severe (severe hypertensions [SBP increase of more than 40] , severe hypotension, significant dyspnea with brochospasm, stridor, and rigors)
• The authors provide a treatment algorithm (Figure 1) based on severity of acute IR.  All reactions are initially treated by stopping infusion, but many can be restarted at a low rate after administration of acetaminophen (mild & moderate), normal saline (mild & moderate), diphenhydramine (moderate), and possibly hydrocortisone (if needed in moderate cases).  While the algorithm suggests the possibility of restarting infusion reaction in severe cases without anaphylaxis, if this is considered, it may be worthwhile to attempt in a hospital setting.
• Typically if infusions are restarted, the rates are 10 mL/hr x 15 minutes –>20 mL/hr x 15 minutes–> 40 mL/hr x 15 minutes –>80 mL/hr x 15 minutes –>100 mL/hr x 15 minutes–>125 mL/hr until completion.
• Following an IR, the authors recommend checking for ATIs and for IFX level.
• Prophylaxis for mild IRs includes the use of acetaminophen and antihistamines (2nd generation antihistamine daily for 5 days prior or first generation antihistamine an hour prior to infusion).  In addition, the infusion should be started at 10 mL/hr
• Prophylaxis for moderate IRs includes the use of acetaminophen and antihistamines and steroids (prednisone 50 mg q12 hr x 3 doses prior or hydrocortisone 100 mg (or equivalent) 20 minutes prior to infusion).  In addition, the infusion should be started at 10 mL/hr
• The authors recommend against premedication in those who have not had IRs. Use of premedication may cause a paradoxical increase in IRs due to symptoms induced by the antihistamine.

Autoimmune Complications:

• Autoantibodies: anti-nuclear antibody (ANA), anti-double-stranded DNA antibody (anti-dsDNA), anti-cardiolipin antibody, antihistone antibody
• Drug-Induced Lupus Erythematosus (DILE) -“the most frequently presenting symptoms, seen in 90% of cases, is symmetric arthralgias.”  Systemic involvement of the kidneys or central nervous system is rare. Treatment is cessation of the offending medication.
• Vasculitis -likely due to the development of circulating immune complexes that deposits into smaller capillaries–>result in a type III hypersensitivity reaction.  The most common manifestation would be palpable purpura due to a leukocytoclastic vasculitis.
• While autoimmune complications can be a class effect, many patients have been able to switch to a different anti-TNF.

Dermatologic Complications:

The authors review both anti-TNF induced psoriasis and eczema.  Treatment should be in conjunction with dermatology.  For psoriasis that involves >5% of body surface area, this could require changing to a different anti-TNF or a different drug class.  For severe cases, “anti-TNF therapy should be discontinued.”

Related blog posts:

• Pattern of Skin Reactions to Anti-TNF Agents | gutsandgrowth
• Treating Allergic Reactions to Infliximab | gutsandgrowth
• Overcoming ATIs | gutsandgrowth
• TNF Antagonists and Psoriasis | gutsandgrowth
• What you might not know about anti-TNF monitoring …
• More Lessons in TNF Therapy (Part 2) | gutsandgrowth
• More NASPGHAN Meeting Notes: IBD Hot Topics | gutsandgrowth

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.