Can Biologics Help with Fatigue? Understanding Treatment and Efficacy

October 10, 2025 •

4 min read

Fatigue is one of the most common and debilitating symptoms reported by patients with chronic inflammatory diseases. But can biologics help with fatigue? Emerging evidence suggests that for many, the answer is a cautious yes, though the effect is often indirect and varies significantly depending on the underlying condition.

Quick Summary

Biologics often lead to small to moderate improvements in fatigue for patients with chronic inflammatory conditions, primarily by reducing the underlying disease activity and inflammation. The response is not universal and can vary greatly by disease and patient, with some even experiencing fatigue as a side effect.

Key Points

Indirect Action: Biologics reduce fatigue primarily by controlling the underlying inflammation and disease activity in conditions like rheumatoid arthritis and inflammatory bowel disease.
Variable Efficacy: The effectiveness of biologics on fatigue is not universal and depends on the specific disease, the patient's individual response, and other contributing factors.
Fatigue as a Side Effect: In some cases, fatigue can be a reported adverse drug reaction of biologics, with some patients experiencing a worsening of tiredness, particularly after a dose.
Not for ME/CFS: Biologics are not an approved treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and trials have not shown consistent success.
Improved Quality of Life: Many studies on biologics show that while the effect on fatigue may be small to moderate, the overall improvement in disease activity, pain, and sleep quality can significantly enhance a patient's quality of life.
Individualized Response: Factors like baseline fatigue severity and the presence of comorbidities like depression or anemia can affect how much improvement a patient experiences.

Fatigue is a complex and multifaceted symptom that significantly impacts the quality of life for millions of people living with chronic inflammatory and autoimmune diseases. While the primary purpose of biologic medications is to target the root cause of these diseases—the dysregulated immune response—many patients report an improvement in their energy levels as a result. However, the relationship between biologics and fatigue is nuanced, and the efficacy is not uniform across all conditions or all individuals.

How Biologics Address Fatigue Through Inflammation

Biologics are a class of drugs that modify the immune system's response by targeting specific proteins, cells, or other components involved in the inflammatory process. This targeted approach differs from traditional immunosuppressants, which suppress the entire immune system more broadly. In chronic inflammatory conditions, persistent inflammation is a key driver of fatigue, and by controlling this inflammation, biologics can alleviate the overwhelming tiredness.

The Indirect Mechanism of Fatigue Reduction

For many patients, the reduction in fatigue is an indirect consequence of the biologic successfully controlling their disease. When inflammation, pain, and other symptoms are managed, a patient's overall health and well-being tend to improve, which can lead to better energy levels. This was demonstrated in a Cochrane review of rheumatoid arthritis (RA) patients, which found that while biologics produced a statistically significant reduction in fatigue, it was unclear whether this was a direct effect or a result of decreased disease activity and inflammation.

Biologics and Fatigue in Specific Conditions

Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA)

In inflammatory rheumatic and musculoskeletal diseases (I-RMDs) like RA and PsA, the link between biologics and fatigue improvement is well-documented. A 2016 Cochrane review found that both anti-TNF and non-anti-TNF biologics led to a small to moderate reduction in patient-reported fatigue in RA. Similarly, a meta-analysis in PsA trials confirmed a small to moderate effect on fatigue, noting that the effect size was higher for pain than for fatigue, suggesting that fatigue is multifactorial.

Inflammatory Bowel Disease (IBD)

Fatigue is a common and debilitating symptom for IBD patients with Crohn's disease and ulcerative colitis.

Improvement with Biologics: A 2023 meta-analysis of randomized, placebo-controlled trials found that biological agents had a small but consistent beneficial effect on fatigue in IBD.
Role of Clinical Remission: A more recent 2025 study highlighted that achieving clinical remission with biologic treatment significantly increases the probability of fatigue disappearance, though fatigue may persist for some even in remission.

Multiple Sclerosis (MS)

Biologics and other disease-modifying therapies (DMTs) for MS show varied effects on fatigue.

Variable Response: Some studies, like the TYNERGY trial on natalizumab, indicated that MS-related fatigue might improve, particularly in patients with more pronounced fatigue at baseline.
Potential Side Effect: Conversely, some patients report fatigue as a side effect of certain DMTs, including natalizumab. Ocrelizumab showed significant improvement in fatigue in one study, while interferon therapy is frequently associated with fatigue.

Chronic Fatigue Syndrome (ME/CFS)

It is important to distinguish fatigue related to inflammatory diseases from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). ME/CFS is a distinct illness with no FDA-approved drugs, and while some immunomodulatory therapies have been explored, large-scale trials have been largely disappointing. Biologics that target inflammation in autoimmune diseases are not approved treatments for ME/CFS, though research continues into potential biological mechanisms.

Factors Influencing Biologics' Effect on Fatigue

The response to biologic treatment for fatigue is not guaranteed and can be affected by multiple factors:

Baseline Fatigue Severity: Patients with more severe fatigue at the start of treatment may see greater improvements.
Co-occurring Conditions: Comorbidities like depression, anemia, and poor sleep quality can influence fatigue levels, even when inflammation is controlled.
Duration of Treatment: Initial improvements in fatigue may occur relatively early in treatment (within the first 6 months) and then fluctuate or stabilize over time.
Individual Response: Patient-reported outcome measures show significant variability, with some patients responding well while others see minimal or no change in fatigue.

Comparison of Biologic Effects on Fatigue in Different Conditions


Condition	Example Biologics	Primary Mechanism for Fatigue Relief	Observed Effect on Fatigue	Key Findings
Rheumatoid Arthritis	Anti-TNF agents (e.g., infliximab, adalimumab), non-anti-TNF (e.g., tocilizumab)	Reduce systemic inflammation and pain	Small to moderate improvement	Often secondary to overall disease control, though can persist even in remission.
Inflammatory Bowel Disease	Anti-TNF agents (e.g., infliximab), integrin blockers (e.g., vedolizumab)	Reduce intestinal inflammation	Small but consistent beneficial effect	Correlates most strongly with achieving clinical remission.
Multiple Sclerosis	Natalizumab, Alemtuzumab	Inhibit leukocyte migration to CNS, T- and B-cell modulation	Variable, with some improvement reported but can also be a side effect	Response varies significantly; benefits may be more prominent in those with higher baseline fatigue.
Chronic Fatigue Syndrome	Investigational agents only	None	Inconclusive/Disappointing	Currently no approved biologics for ME/CFS; not an appropriate treatment.

Conclusion

For many patients with chronic inflammatory diseases like rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis, biologics can offer a significant, albeit often moderate, improvement in fatigue. The primary mechanism appears to be an indirect one, where controlling the underlying inflammation, pain, and disease activity leads to a subsequent improvement in energy levels. However, it is crucial to recognize that fatigue is a complex symptom influenced by various factors, and biologics are not a guaranteed cure. Patients should have realistic expectations and discuss the potential for both benefit and side effects with their healthcare provider. For conditions like ME/CFS, biologics are not an approved treatment. While biologics have revolutionized the management of many chronic inflammatory diseases, a holistic approach that also addresses comorbidities and lifestyle factors is essential for optimal fatigue management. For more information, the Arthritis Foundation offers extensive resources on managing fatigue associated with chronic conditions.

Frequently Asked Questions

No, the effect of biologics on fatigue is not universal. The response varies significantly depending on the specific drug, the patient's underlying condition, and individual factors.

Biologics help reduce fatigue by controlling the underlying inflammatory process that drives many autoimmune diseases. This reduction in disease activity and pain indirectly leads to an improvement in energy levels for many patients.

Yes, some patients report fatigue as a side effect of biologic medication, particularly shortly after an injection or infusion. For these individuals, it may be a recurring adverse drug reaction.

There are no approved biologics for treating ME/CFS. While some immunomodulators have been studied, larger controlled trials have generally been disappointing.

Initial improvements can often be seen within the first six months of treatment. However, the timeframe varies widely, and some studies show that fatigue improvements may take longer or plateau.

If fatigue persists despite biologic treatment, your doctor may investigate other contributing factors such as anemia, poor sleep, or depression. Fatigue can be multifactorial and may not resolve solely by controlling inflammation.

Yes, studies in inflammatory bowel disease and other conditions show that achieving clinical remission is strongly associated with a higher probability of fatigue disappearance. However, some patients who achieve remission may still experience persistent fatigue.