Does Hydroxychloroquine Help Osteoarthritis? A Review of the Clinical Evidence

Osteoarthritis (OA) is a 'silent epidemic,' with over 300 million people worldwide suffering from hip or knee OA. While treatments for this degenerative joint disease are limited, many wonder, does hydroxychloroquine help osteoarthritis? The current scientific consensus, based on high-quality trials, indicates it does not.

Quick Summary

Meta-analyses and large randomized controlled trials have consistently found that hydroxychloroquine offers no significant benefit for reducing pain or improving function in hand and knee osteoarthritis compared to a placebo.

Key Points

• No Proven Efficacy: Large-scale clinical trials and systematic reviews show that hydroxychloroquine is not more effective than a placebo for treating osteoarthritis pain or function.

• Designed for Inflammatory Arthritis: Hydroxychloroquine is a DMARD specifically effective for autoimmune diseases like rheumatoid arthritis and lupus, not for the degenerative nature of osteoarthritis.

• Off-Label Use Discouraged: Due to the lack of evidence for benefit, medical societies discourage the off-label use of HCQ for osteoarthritis.

• Established Alternatives Exist: Effective treatments for osteoarthritis include exercise, weight management, topical or oral NSAIDs, and physical therapy, all of which have proven efficacy.

• Potential Risks without Benefit: Taking HCQ for an unproven indication like OA exposes patients to potential side effects, such as eye and heart issues, without the compensating therapeutic gain.

• Clear Clinical Distinction: The distinction between HCQ's effectiveness in inflammatory arthritis versus its ineffectiveness in degenerative osteoarthritis is an important clinical takeaway for patient care.

Understanding Hydroxychloroquine's Role in Arthritis

Hydroxychloroquine (HCQ), a well-established disease-modifying anti-rheumatic drug (DMARD), is primarily known for its effectiveness in treating inflammatory conditions such as rheumatoid arthritis (RA) and lupus. Its mechanism involves modulating the immune system, calming the inflammation that drives these autoimmune diseases. The success of HCQ in RA led some researchers to investigate its potential for treating osteoarthritis, particularly since evidence suggests an inflammatory component is involved in OA pathology.

The Rationale for HCQ in Osteoarthritis

Unlike the autoimmune-driven inflammation in RA, OA is traditionally considered a degenerative 'wear-and-tear' disease involving cartilage breakdown. However, the role of low-grade inflammation in OA has gained attention, with studies showing inflammatory markers in osteoarthritic cartilage and joints. Given HCQ's known anti-inflammatory and immunomodulatory properties, it was hypothesized that it could be a useful treatment for inflammatory forms of hand and knee OA. Early, smaller studies sometimes reported inconsistent findings, which fueled ongoing investigation.

Clinical Trials and Systematic Reviews Debunk HCQ for OA

Several large, rigorous clinical trials have now definitively addressed the question of HCQ's efficacy in osteoarthritis. The findings from these methodologically sound studies have been consistent and disappointing for those hoping for a new OA drug.

• The HERO Trial (2018): This large, randomized, placebo-controlled trial included 248 adults with hand OA and significant pain. After 12 months, researchers found no significant difference in pain levels, function, or grip strength between the HCQ and placebo groups. The study concluded that HCQ offers no benefit over placebo for hand osteoarthritis.
• The OA-TREAT Trial (2021): Focusing specifically on erosive hand OA (a more inflammatory subset), this randomized, placebo-controlled trial followed patients for 52 weeks. It found HCQ was no more effective than placebo in improving pain, function, or preventing radiographic progression.
• Systematic Review and Meta-Analysis (2021): A comprehensive review, including six RCTs (four on hand OA and two on knee OA) with over 800 patients, analyzed the collective evidence. The high-quality evidence showed no clinically important pain reduction or improvement in physical function with HCQ compared to placebo in hand or knee OA. The conclusion was clear: HCQ has no benefit for treating OA and off-label use should be discouraged.

Comparison of HCQ vs. Proven OA Treatments

HCQ's ineffectiveness in OA is in stark contrast to other treatments with demonstrated benefits. A structured comparison highlights the differences:

Feature	Hydroxychloroquine (HCQ)	Established Osteoarthritis Treatments
Effectiveness for OA Pain	No significant benefit shown over placebo in large clinical trials.	Proven pain relief for many people with mild to moderate pain.
Mechanism of Action	Immunomodulatory; targets systemic inflammation primarily useful in autoimmune diseases like RA.	Varied mechanisms; include muscle strengthening, inflammation reduction (NSAIDs), joint lubrication (injections).
Time to Effect	Months for inflammatory conditions; no demonstrated effect for OA.	Variable; some effects can be immediate (topical NSAIDs, injections), while lifestyle changes require longer-term commitment.
Safety Profile	Generally well-tolerated, but carries risks like retinal toxicity (rare at standard doses) and cardiac side effects with long-term use.	Side effects vary by treatment. NSAIDs can have GI and cardiovascular risks, while physical therapy carries minimal risk.
Regulatory Approval	Not approved for osteoarthritis; off-label use is discouraged.	Approved for OA management, supported by clinical guidelines.

Effective Alternatives for Osteoarthritis Management

Given the lack of evidence for hydroxychloroquine, patients with osteoarthritis should focus on established, proven management strategies. These often involve a multi-pronged approach that combines non-pharmacological methods with appropriate medication.

Non-Pharmacological Strategies:

• Exercise: Low-impact activities like swimming, walking, and tai chi strengthen muscles around the joints, improve flexibility, and reduce pain. Physical therapy can provide personalized exercise plans.
• Weight Management: Losing excess weight significantly reduces the load on weight-bearing joints like the knees and hips, alleviating pain.
• Physical and Occupational Therapy: Therapists can teach exercises, strategies for daily tasks, and proper body mechanics to minimize joint stress.
• Supportive Devices: Canes, walkers, and braces can offload pressure and provide stability to affected joints.

Pharmacological Strategies:

• Topical Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Creams or gels applied directly to the affected joint provide localized pain and inflammation relief with fewer systemic side effects than oral NSAIDs.
• Oral NSAIDs: Medications like ibuprofen and naproxen can relieve pain and inflammation. They should be used with caution due to potential side effects.
• Acetaminophen: Used for mild to moderate pain, though some guidelines have downgraded its recommendation due to limited efficacy.
• Injections: Corticosteroid injections can provide temporary relief from inflammation and pain. Hyaluronic acid injections may offer cushioning for the knee, though efficacy varies.

Conclusion: Looking Beyond Misconceptions

The extensive clinical research available today provides a clear and consistent message: hydroxychloroquine does not help osteoarthritis. While the initial hypothesis for its use in OA was based on a sound understanding of its anti-inflammatory properties, well-conducted trials have consistently demonstrated its ineffectiveness for pain and function in hand and knee OA. The off-label use of this medication for osteoarthritis should therefore be avoided. Instead, patients and clinicians should focus on proven, guideline-recommended treatments, including targeted exercise, weight management, and established pain-relieving medications like topical NSAIDs. Understanding the difference between inflammatory arthritis (like RA) where HCQ is effective, and degenerative arthritis (like OA) where it is not, is crucial for proper and effective patient care.

For more information on evidence-based treatments for osteoarthritis, consult resources such as the American College of Rheumatology.

Comparison Table

Feature	Hydroxychloroquine (HCQ)	Established Osteoarthritis Treatments
Effectiveness for OA Pain	No significant benefit shown over placebo in large clinical trials.	Proven pain relief for many people with mild to moderate pain.
Mechanism of Action	Immunomodulatory; targets systemic inflammation primarily useful in autoimmune diseases like RA.	Varied mechanisms; include muscle strengthening, inflammation reduction (NSAIDs), joint lubrication (injections).
Time to Effect	Months for inflammatory conditions; no demonstrated effect for OA.	Variable; some effects can be immediate (topical NSAIDs, injections), while lifestyle changes require longer-term commitment.
Safety Profile	Generally well-tolerated, but carries risks like retinal toxicity (rare at standard doses) and cardiac side effects with long-term use.	Side effects vary by treatment. NSAIDs can have GI and cardiovascular risks, while physical therapy carries minimal risk.
Regulatory Approval	Not approved for osteoarthritis; off-label use is discouraged.	Approved for OA management, supported by clinical guidelines.

Frequently Asked Questions

Is hydroxychloroquine the same as Plaquenil?

Yes, Plaquenil is a common brand name for the generic drug hydroxychloroquine.

Why was hydroxychloroquine initially considered for osteoarthritis?

HCQ was considered because of its anti-inflammatory properties, and researchers hypothesized it might help combat the low-grade inflammation now known to be involved in the pathology of osteoarthritis.

What is the difference between rheumatoid arthritis and osteoarthritis?

Rheumatoid arthritis is an autoimmune disease where the body's immune system attacks its own joints, while osteoarthritis is a degenerative joint disease involving cartilage breakdown.

What is the best treatment for osteoarthritis pain?

Effective treatments include a combination of exercise, weight management, physical therapy, and medications like topical NSAIDs. The best approach depends on the individual and should be determined with a healthcare provider.

Are there any side effects from taking hydroxychloroquine?

Yes, while generally well-tolerated at standard doses, potential side effects include gastrointestinal issues, rash, and, rarely, visual changes or heart problems, especially with high-dose or long-term use.

Should I continue taking hydroxychloroquine for my osteoarthritis if my doctor prescribed it?

You should follow your doctor's instructions. If you have concerns about the prescription's effectiveness, discuss the evidence presented here with your healthcare provider to explore alternative, more proven treatment options.

Does HCQ help with erosive hand osteoarthritis?

No, a large trial (OA-TREAT) that specifically investigated HCQ for inflammatory and erosive hand osteoarthritis found it was no more effective than a placebo for improving pain, function, or radiographic outcomes.