Does Hydroxychloroquine Lower CRP? Understanding the Anti-Inflammatory Effects

October 10, 2025 •

4 min read

In a study of rheumatoid arthritis patients, those treated with hydroxychloroquine at a 400 mg/day dose were found to have significantly lower average CRP values compared to non-treated groups, which helps to answer the question: Does hydroxychloroquine lower CRP? The drug works gradually by modulating the immune system to reduce systemic inflammation.

Quick Summary

Hydroxychloroquine exhibits anti-inflammatory properties by inhibiting key immune pathways, which can lead to a reduction in C-reactive protein (CRP) levels in patients with autoimmune diseases. The effect is typically slow and more pronounced in chronic, systemic inflammation rather than acute inflammatory spikes. Evidence supports its role in decreasing inflammatory markers, though it is often part of a broader treatment strategy.

Key Points

Indirect CRP Reduction: HCQ lowers CRP by dampening the overall autoimmune inflammatory response, primarily by inhibiting pro-inflammatory cytokines like IL-6.
Slow Onset of Action: The CRP-lowering effect is not immediate; it typically takes 6 to 12 weeks of consistent use to become clinically noticeable.
Modest Effect: HCQ's effect on CRP is generally more modest compared to more potent DMARDs or biologics, making it suitable for milder disease activity.
Evidence in RA and pSS: Studies have specifically shown a significant reduction in CRP in patients with rheumatoid arthritis and Sjögren's syndrome treated with HCQ.
Part of Broader Benefit: The CRP reduction is part of HCQ's overall benefit, which includes reducing disease flares, preventing long-term damage, and improving survival in conditions like lupus.
Mechanism of Action: HCQ interferes with key cellular processes like endosomal acidification and Toll-like receptor signaling, which reduces the production of inflammatory mediators.

What is Hydroxychloroquine and CRP?

Hydroxychloroquine (HCQ), also known by the brand name Plaquenil, is a disease-modifying anti-rheumatic drug (DMARD) used to treat various autoimmune conditions, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Its anti-inflammatory properties were discovered serendipitously during its use as an antimalarial drug.

C-reactive protein (CRP) is a protein produced by the liver. Its levels in the blood rise in response to inflammation. Doctors measure CRP to monitor disease activity in inflammatory conditions and assess the effectiveness of treatment. In general, the goal of HCQ therapy in autoimmune disease is to reduce this underlying inflammatory activity, which can be reflected in a drop in CRP levels.

The Anti-Inflammatory Mechanism of HCQ

While the exact mechanism of HCQ is still being studied, research suggests it affects the immune system in several key ways, leading to its anti-inflammatory effects and potential for lowering CRP. The primary mechanisms involve interfering with key cellular processes that drive the autoimmune response. These include:

Increasing Endosomal pH: As a weak base, HCQ accumulates in acidic cellular compartments like endosomes and lysosomes. This raises their internal pH, which disrupts the function of numerous enzymes and cellular pathways.
Inhibiting Toll-like Receptors (TLRs): HCQ blocks the activation of intracellular TLRs (specifically TLR7 and TLR9), which are essential for recognizing nucleic acids and initiating an innate immune response. By inhibiting this, HCQ reduces the production of pro-inflammatory cytokines.
Reducing Cytokine Production: By modulating the immune response, HCQ decreases the levels of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α). IL-6 is a key cytokine that signals the liver to produce CRP, so reducing IL-6 directly impacts CRP levels.
Blocking Calcium Signaling: HCQ can impair the release of calcium from the endoplasmic reticulum, which is a necessary step for the activation of T and B immune cells. This further suppresses the autoimmune response.

Clinical Evidence: HCQ and CRP Levels

Several studies have shown a correlation between HCQ treatment and reduced CRP levels, although the magnitude and speed of this effect can vary based on the patient's condition and individual response. Evidence from clinical settings includes:

Rheumatoid Arthritis (RA): A study comparing HCQ-treated RA patients with non-treated patients found that the HCQ group, particularly those on a 400 mg daily dose, had significantly lower average CRP values. The American College of Rheumatology (ACR) recommends HCQ as an initial treatment for mild RA.
Systemic Lupus Erythematosus (SLE): HCQ is a cornerstone therapy for SLE, known to reduce disease flares, decrease organ damage accrual, and improve long-term survival. While its immunomodulatory effects are well-established, CRP levels in SLE patients are less frequently used as a primary marker compared to RA, but the drug's overall anti-inflammatory effect contributes to better control of inflammatory markers.
Sjögren's Syndrome (pSS): A systematic review and meta-analysis of studies in patients with primary Sjögren's syndrome (pSS) found that HCQ treatment significantly reduced CRP levels, along with other markers like erythrocyte sedimentation rate (ESR).
Conflicting Evidence: It is important to note that HCQ's effect on CRP is not always dramatic or guaranteed. Studies involving COVID-19 and HCQ, for example, found no correlation between HCQ concentrations and CRP levels. Additionally, a study on osteoarthritis found mixed results regarding CRP changes.

Why HCQ's Effect on CRP Can Be Modest

Unlike more potent immunosuppressants or biologics, HCQ is a slow-acting drug that takes time to reach its full therapeutic effect. Patients may not notice significant benefits for 6 to 12 weeks or more. Factors that influence the degree of CRP reduction include:

Baseline Inflammation: HCQ may have a more pronounced effect in chronic, lower-grade inflammatory states compared to severe, acute flares.
Combination Therapy: HCQ is often used in combination with other DMARDs or biologics, which can make it difficult to isolate the contribution of HCQ alone to the overall reduction in CRP.
Disease Type: As seen with SLE vs. RA, HCQ's impact on specific biomarkers can vary depending on the underlying autoimmune disease and its primary inflammatory pathways.

Comparison with Other DMARDs for CRP Reduction

For patients with more severe or aggressive autoimmune disease, HCQ's anti-inflammatory effect might not be sufficient on its own. Other DMARDs or biologics often have a more rapid and robust impact on CRP levels.


Feature	Hydroxychloroquine (HCQ)	Methotrexate (MTX)	Biologics (e.g., TNF Inhibitors)
Mechanism	Immunomodulatory; inhibits TLRs, reduces cytokines, alters lysosomal pH.	Potent immunosuppressant; inhibits folate metabolism, reduces inflammatory cell proliferation.	Targeted therapy; blocks specific inflammatory pathways (e.g., TNF-α).
Onset	Slow; 6-12 weeks to see benefit.	Faster than HCQ; typically within 4-6 weeks.	Fastest; some patients feel improvement within weeks.
CRP Reduction	Modest, but statistically significant in many cases, part of overall anti-inflammatory effect.	More powerful reduction, especially in RA.	Highly effective, often leading to substantial CRP drops.
Target Conditions	Mild RA, SLE, pSS.	Moderate-to-severe RA, psoriasis, others.	Moderate-to-severe RA, SLE, others; when conventional DMARDs fail.

The Verdict: Does Hydroxychloroquine Lower CRP?

Yes, hydroxychloroquine does lower CRP, particularly in the context of chronic autoimmune diseases like rheumatoid arthritis and Sjögren's syndrome. Its mechanism involves a multifaceted immunomodulatory and anti-inflammatory action that reduces the overall inflammatory burden on the body, which is reflected in lower CRP levels. However, its effect is generally modest and slow compared to more aggressive therapies like methotrexate or biologics.

The reduction in CRP is just one part of the drug's overall benefit. As a safe and well-tolerated long-term therapy, HCQ helps prevent disease flares and long-term damage, contributing significantly to improved quality of life for patients with autoimmune conditions. Consistent use as prescribed is crucial for experiencing its full therapeutic effect.

For more information on rheumatic conditions and their management, consult the resources of the American College of Rheumatology.

Frequently Asked Questions

Hydroxychloroquine is slow-acting, so it can take anywhere from 6 to 12 weeks of consistent daily use before you may start to see a measurable reduction in CRP levels.

No, hydroxychloroquine is not considered a strong CRP reducer compared to other more aggressive DMARDs or biologics. Its effect is more gradual and modest, often making it a suitable choice for milder inflammatory conditions.

Not necessarily. The effect can be disease-specific and depends on the baseline level and type of inflammation. While studies show reduction in RA and pSS, a study on COVID-19, for example, showed no correlation.

HCQ works by modulating the immune system. It inhibits Toll-like receptors and increases the pH within cellular compartments, which reduces the production of pro-inflammatory cytokines like IL-6. Since IL-6 signals the liver to produce CRP, its reduction leads to lower CRP levels.

Yes, tracking CRP levels is a standard practice to monitor disease activity and treatment response, though doctors will also consider clinical symptoms. Because HCQ works slowly, meaningful changes in CRP will take time.

Methotrexate is generally faster and more potent at reducing inflammation and CRP levels than hydroxychloroquine. HCQ is typically used for less severe cases or in combination with other drugs.

For very high CRP levels indicative of severe disease, doctors may initially opt for more potent treatments or use HCQ as part of a combination therapy. HCQ's effect might not be strong enough alone to control severe inflammation.