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British Journal of Healthcare and Medical Research - Vol. 11, No. 5
Publication Date: October 25, 2024
DOI:10.14738/bjhmr.115.17651.
Magbri, A., & El-Magbri, M. (2024). Use of Biologic Medicine in Autoimmune and Inflammatory Diseases; Effectiveness, Side-Effects
and Loss of Strength in the Long Run, Then What? British Journal of Healthcare and Medical Research, Vol - 11(5). 95-97.
Services for Science and Education – United Kingdom
Use of Biologic Medicine in Autoimmune and Inflammatory
Diseases; Effectiveness, Side-Effects and Loss of Strength in the
Long Run, Then What?
Awad Magbri
Marshfield Medical Centre-Weston,
WI USA, Detroit Medical Center, MI USA
Mariam El-Magbri
Marshfield Medical Centre-Weston,
WI USA, Detroit Medical Center, MI USA
ABSTRACT
The use of biological medicines has revolutionized the treatment of various chronic
and immune-mediated diseases, offering improved outcomes in gastrointestinal
disorders like ulcerative colitis (UC) and Crohn’s disease (CD), rheumatological
diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis
(RA), and skin conditions like psoriatic arthritis (PsA) and eczema, among others.
These therapies, often in the form of monoclonal antibodies or cytokine inhibitors,
target specific immune pathways, providing relief where traditional treatments
often fall short. While these drugs have transformed the management of these
conditions, their long-term efficacy and safety present significant challenges,
particularly with the emergence of subtle side effects, such as the development of
new autoimmune diseases and neutralizing antibodies that render these drugs less
effective over time.
Keywords: Biologic therapy, Neutralizing antibodies, Anti-drug antibodies, Autoimmune
disease, Inflammatory disease.
MECHANISMS OF BIOLOGICS AND THEIR IMPACT ON THE IMMUNE SYSTEM
Biologics, especially monoclonal antibodies, work by specifically targeting molecules involved
in immune system activation, such as TNF-alpha, IL-6, and B-cell activators. This precision
allows for the control of excessive immune responses in autoimmune and inflammatory
conditions, providing symptom relief and disease control. However, by altering immune system
activity, these drugs can inadvertently trigger new autoimmune diseases or dysregulate other
immune processes. For example, patients treated with TNF inhibitors for one autoimmune
condition, such as RA, have occasionally developed other conditions like drug-induced lupus,
autoimmune thyroid diseases, or psoriasis.
While these effects are uncommon, they raise concerns about the long-term impact of biologics
on immune system balance. The key challenge is identifying why certain patients develop these
autoimmune sequelae and how to mitigate these risks without undermining the therapeutic
benefits.
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British Journal of Healthcare and Medical Research (BJHMR) Vol 11, Issue 05, October-2024
Services for Science and Education – United Kingdom
DEVELOPMENT OF NEUTRALIZING ANTIBODIES
One of the major issues with biologic therapies is the potential for patients to develop anti-drug
antibodies (ADAs), particularly neutralizing antibodies. These antibodies recognize and
neutralize the biologic drug, reducing its efficacy. For example, patients treated with infliximab
(used in UC and CD) or adalimumab (used in RA, PsA, and IBD) may develop ADAs, especially
after prolonged exposure. When this occurs, the biologic is no longer effective in controlling the
disease, leading to a return of symptoms and flares.
Several factors contribute to the development of neutralizing antibodies, including:
• Immunogenicity of the biologic itself: Fully humanized or human monoclonal
antibodies tend to be less immunogenic compared to chimeric or murine-based
biologics.
• Intermittent treatment regimens: Longer gaps between doses can lead to antibody
formation, as the immune system is given time to recognize the biologic as foreign.
• Co-treatment with immunosuppressants: In some cases, co-prescribing
immunosuppressive drugs, such as methotrexate, can reduce the likelihood of ADA
development by dampening the overall immune response.
The presence of neutralizing antibodies limits the effectiveness of biologics over time, forcing
clinicians to switch therapies or increase dosages, which may lead to additional side effects or
diminishing returns.
THE LONG-TERM EFFICACY CHALLENGE: WHAT HAPPENS NEXT?
When biologics become ineffective due to neutralizing antibodies or the emergence of new
autoimmune diseases, physicians are faced with difficult treatment decisions. Several options
exist, but each comes with its own challenges:
• Switching to another biologic within the same class: This approach can sometimes
restore efficacy, as the patient may respond differently to a similar biologic with slightly
altered molecular structure. For instance, switching from infliximab to adalimumab in
Crohn’s disease can offer temporary benefit, although the risk of ADA development
persists.
• Switching to a different class of biologics: If a patient develops antibodies to a TNF
inhibitor, switching to another biologic targeting a different pathway, such as an IL- 12/IL-23 inhibitor (e.g., ustekinumab for IBD) or IL-17 inhibitors (for PsA and
psoriasis), might be more effective. This strategy, however, also comes with the
possibility of new side effects and unknown long-term safety issues.
• Use of small molecules: Small molecule inhibitors, such as Janus kinase (JAK)
inhibitors or S1P modulators, are non-biologic alternatives that target intracellular
signaling pathways involved in immune responses. These medications, like tofacitinib
(for RA and UC), may be useful when biologics fail, although they are also associated
with their own safety concerns, including an increased risk of infections and
malignancies.
• Re-induction with the same biologic, combined with immunosuppression: In some
cases, clinicians may attempt to reintroduce the same biologic while adding
immunosuppressive drugs to prevent antibody formation. This approach requires
careful balancing of immunosuppressive therapy to avoid additional complications such
as infections or malignancy.