Pharmacist Strategies for Navigating Supplement Use in Patients on TNF Inhibitors

Tumor necrosis factor (TNF) inhibitors, including adalimumab (Humira; AbbVie), etanercept (Enbrel; Amgen), and infliximab (Remicade; Janssen Biotech, Inc), have significantly improved the treatment landscape for chronic inflammatory and autoimmune conditions such as rheumatoid arthritis, ulcerative colitis, Crohn disease, and psoriasis. Although they offer substantial therapeutic benefits, these biologics present unique challenges for patients, particularly concerning immunosuppression, potential adverse effects (AEs), and common misconceptions about "immune boosting." Pharmacists, with their accessibility and trusted relationships with patients, are uniquely positioned to address these complexities through evidence-based education and proactive counseling.

Patient Perspectives and the Risk of Unsupervised Supplementation

Initiating a biologic therapy can often feel daunting for patients. Concerns frequently include fears regarding immune suppression, anxiety related to injectable medications, high out-of-pocket expenses, and a sense of losing control over their health journey. Potential AEs, such as increased susceptibility to infections, fatigue, dermatologic reactions, and malignancies, can exacerbate these anxieties. Poor adherence to prescribed therapy is common, particularly when patients do not fully grasp how TNF inhibitors function to regulate—rather than destroy—the immune response.¹ In an effort to self-manage AEs or compensate for what they perceive as immune "weakness," many patients turn to OTC supplements or herbal products, often marketed as "immune boosters," unaware of the potential for harm or interference with their prescribed therapy.²

The Overlooked Risk: Potential Interactions and AEs

The combined use of biologic therapies and unsupervised supplementation poses a significant, often underappreciated, risk. Supplements (eg, zinc, high-dose vitamin D, echinacea, and elderberry) are frequently promoted for immune support; however, when taken by patients already on immunomodulatory treatment like TNF inhibitors, these products can inadvertently modulate immune function in unintended ways.³

Zinc, although essential for immune function, has been shown in mouse tumor models to promote tumor progression by fostering a protumorigenic environment mediated by T cells. High zinc intake was found to facilitate tumor progression by increasing the frequency of Foxp3⁺ regulatory T cells (Tregs), which are implicated in shaping immunosuppressive environments within tumors.^4,5 Elevated zinc intake also increased the expression of PD‑1 on CD4⁺, CD8⁺, and γδ T cells, allowing cancer cells to evade immune detection and destruction.⁵ Furthermore, high zinc intake negatively regulates antitumor immune response by FOXO1-mediated regulation of Treg cell differentiation and function, and also suppresses α‑PD‑1 tumor immune checkpoint therapy response.⁵ High doses of zinc supplements, especially with long-term usage, have been reported to have adverse effects such as a suppressed immune system and copper deficiency.⁴ In the context of TNF inhibitors, overstimulating certain immune pathways or promoting immunosuppressive cell populations may not only diminish therapeutic effect, but could potentially contribute to disease flare or paradoxical inflammation.³

Echinacea preparations, particularly Echinacea purpurea, are widely studied herbal medicines often used to treat cough, cold, seasonal flu, and upper respiratory infections. Because of their purported antiviral and immunomodulatory properties, they are often suggested as potential candidates for novel coronaviruses. Although some reports suggest an immunosuppressive nature ascribed to inhibitory actions on cytokine release,⁶ other studies demonstrates potent immunomodulatory properties.⁷ Echinacea's effects on immune cells—including monocytes, macrophages, natural killer cells, T cells, and dendritic cells—are well demonstrated.^6,8 It is theoretically contraindicated in patients with autoimmune diseases or those receiving immunomodulatory therapy due to its potential immune-stimulating effect. The use of "immune boosters" like echinacea in patients on biologics can disrupt the carefully calibrated immune modulation provided by the prescribed treatment.³

Other supplements like high-dose vitamin D, while sometimes appropriate to address deficiencies, carry risks of hypercalcemia, fatigue, and renal complications with excessive dosing.³ Vitamin D also contributes to immune cell activities,⁹ and has been shown to synergistically induce regulatory T cells with zinc in an in vitro human lymphocyte study.¹⁰ Elderberry, another supplement marketed for immune support, is noted for its potential to modulate cytokine expression; in vitro studies show both increased proinflammatory cytokines (eg, IL‑6, TNF‑α) and decreased cytokine levels depending on preparation and context.^11,12 Unsupervised use of these agents, especially in combination with powerful immunomodulatory drugs, introduces unpredictable variables into the patient’s treatment regimen.

Pharmacist-Led Strategies for Safer Supplement Use

Pharmacists are critical health care providers who can help patients navigate the complexities of supplement use while on TNF inhibitor therapy. Key strategies include the following:

• Comprehensive Medication Reviews: Conduct routine medication therapy management sessions to thoroughly review all medications, including OTC products, vitamins, and herbal supplements. This helps identify potential nonadherence, address patient concerns, and uncover supplement use that could interfere with TNF inhibitor therapy.
• Targeted Counseling on Immune Modulation: Use clear, patient-friendly language and, if applicable, visuals or analogies to explain how biologics work to restore immune balance rather than causing "blanket suppression." Clarify misconceptions about the need to "boost" immunity, which can be counterproductive when the goal is immune regulation.¹³
• Educate on Specific Supplement Risks: Directly ask patients about their use of zinc, echinacea, elderberry, and high-dose vitamin D. Counsel them on the potential risks associated with "immune boosters," explaining how these can disrupt the intended immune modulation provided by TNF inhibitors.
• Evidence-Based Supplement Guidance: Advocate against unsupervised supplementation. For essential nutrients like vitamin D or iron, guide patients to discuss testing serum levels with their prescriber before starting supplementation. Emphasize that even seemingly harmless supplements can have unintended effects on the immune system, particularly in the context of immunomodulatory therapy.
• Collaborative Care Coordination: Serve as a vital liaison between patients and prescribers. This involves flagging concerns about supplement use, ensuring appropriate lab monitoring, and reporting potential supplement-related interactions or adverse reactions to the health care team.

Conclusion

Pharmacists play an indispensable role in ensuring the safe and effective use of TNF inhibitors. By proactively identifying and addressing the risks associated with unsupervised supplementation—especially with products marketed as "immune boosters,” zinc, and echinacea—pharmacists can empower patients with accurate information. Counseling should be tailored and culturally sensitive, focusing on educating patients about the importance of immune balance over potentially disruptive immune stimulation. Through personalized education, proactive monitoring, and collaborative care coordination, pharmacists can help patients overcome anxieties, improve adherence, and ultimately achieve better outcomes from their complex treatment regimens. As frontline health care providers, advocating for evidence-based guidance on supplement use is crucial to promote patient safety and optimize therapeutic success.

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