Efficacy and Safety of Iguratimod Combined with Yunke Injection in the Treatment of Ankylosing Spondylitis

This retrospective cohort study demonstrates that combining Iguratimod with Yunke injection is a safe and effective alternative treatment for Ankylosing Spondylitis patients with contraindications to biologics or JAK inhibitors, offering superior disease activity improvement and reduced NSAID dependency compared to Iguratimod monotherapy without increasing adverse reactions.

The Gist

The Big Picture: A "Plan B" for a Stubborn Back Problem

Imagine Ankylosing Spondylitis (AS) as a relentless construction crew inside your spine. They are constantly building "glue" (scar tissue) and "fences" (bone spurs) between your vertebrae, slowly turning your flexible spine into a solid, stiff block of concrete. This causes pain, stiffness, and makes it hard to move.

Usually, doctors have a "Super Tool" to stop this crew: Biologics (powerful immune-system reset buttons) or JAK inhibitors (smart bombs that stop inflammation).

However, there's a catch.
For some patients, using these Super Tools is like trying to fight a fire with a flamethrower—it might work, but it could accidentally burn down the house. Specifically:

• If a patient has a history of cancer, these drugs might wake up sleeping cancer cells.
• If a patient has a history of Tuberculosis (TB) (a lung infection), these drugs might wake up the dormant bacteria, causing a dangerous outbreak.

The Question: What do you do for patients who need help but cannot use the Super Tools?

The Experiment: A New "Duo" Team

This study tested a new combination therapy for these specific high-risk patients. Think of it as assembling a specialized "Duo Team" to fight the construction crew without the dangerous side effects.

The Duo:

1. Iguratimod: A small, synthetic pill. Think of it as a peacekeeper. It calms down the angry immune cells and stops them from shouting inflammatory orders, but it doesn't knock them out completely (so it's safer for cancer/TB patients).
2. Yunke Injection: A liquid medicine containing a special element (Technetium). Think of this as a repair crew and a shield. It soothes the pain, reduces inflammation, and actively helps repair the bone and cartilage damage, while also acting as a shield against the "glue" building up.

The Setup:

• The Observation Group (30 patients): Took the Peacekeeper pill + the Repair Crew injection. They only took painkillers (NSAIDs) if the pain was unbearable.
• The Control Group (18 patients): Took the Peacekeeper pill alone. They relied heavily on painkillers to get by.

Both groups were followed for 24 months (two years).

The Results: The Duo Wins

After two years, the results were clear. The "Duo Team" (Iguratimod + Yunke) worked significantly better than the pill alone.

1. Quieting the Noise (Inflammation)

• The Analogy: Imagine the body is a room full of screaming people (inflammation). Both groups got quieter, but the Duo Team's room was almost silent.
• The Data: The Duo group had much lower levels of inflammation markers (CRP and ESR) than the control group.

2. Moving Freely (Function & Pain)

• The Analogy: The control group was like a person walking with a heavy backpack; they could move, but it was hard. The Duo group was like someone who took the backpack off. They could bend, twist, and move with much less pain and stiffness.
• The Data: The Duo group saw a bigger drop in pain scores and functional disability scores (BASFI).

3. Stopping the Concrete (Spine Damage)

• The Analogy: This is the most important part. The "construction crew" was building concrete bridges between the spine bones. The Duo group slowed down this construction significantly more than the control group.
• The Data: The Duo group had less progression of bone damage (mSASSS scores) over the two years.

4. Less Painkillers Needed

• The Analogy: The control group had to take a lot of over-the-counter painkillers (NSAIDs) just to function. The Duo group needed very few.
• The Data: The Duo group used significantly less NSAIDs. This is huge because long-term painkiller use can hurt your stomach and kidneys.

Safety: Did the "Peacekeeper" Fail?

The biggest fear was: Did this new combo wake up the TB or the cancer?

The Answer: No.

• Tuberculosis: None of the patients with a history of TB had a relapse. The "sleeping bacteria" stayed asleep.
• Cancer: None of the patients with a history of cancer had a recurrence.
• Side Effects: The only minor issue was a slight bump in liver enzymes in a few people (likely due to other factors like fatty liver), which was easily fixed with a short course of liver-protecting medicine. No one had to stop the treatment permanently.

The Conclusion: A Safe Harbor

This study suggests that for patients who are "locked out" of using the powerful new biologics because of cancer or TB risks, this Iguratimod + Yunke Injection combination is a fantastic "Plan B."

It acts like a gentle but effective shield:

• It stops the pain.
• It slows down the spine turning into concrete.
• It reduces the need for harsh painkillers.
• And most importantly, it doesn't wake up the dangerous monsters (cancer or TB) that the other drugs might trigger.

In short: For these specific patients, this duo offers a safe, effective way to keep their spines flexible and their lives moving, without the scary risks of the standard heavy-duty treatments.

Technical Summary

1. Problem Statement

Clinical Gap: Ankylosing Spondylitis (AS) is a chronic inflammatory disease typically treated with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), biologics (TNF-α/IL-17 inhibitors), and JAK inhibitors. However, these advanced therapies carry significant risks for specific patient subgroups, including:

• Tuberculosis (TB) Risk: Biologics and JAK inhibitors can reactivate latent TB or increase susceptibility to active TB.
• Malignancy Risk: Patients with a history of cancer or high risk of tumor recurrence may be contraindicated for certain immunosuppressants.
• Cardiovascular Risk: JAK inhibitors carry specific cardiovascular warnings.

Objective: There is an urgent need for safe, effective alternative treatments for AS patients who cannot tolerate or are contraindicated for biologics and JAK inhibitors due to TB history, cancer history, or other contraindications. This study investigates the efficacy and safety of combining Iguratimod (a small-molecule synthetic DMARD) with Yunke Injection (Technetium [99Tc] Methylenediphosphonate Injection).

2. Methodology

Study Design: Single-center, retrospective cohort study.
Population:

• Total Screened: 1,800 AS patients treated between Jan 1, 2020, and Dec 31, 2023.
• Inclusion Criteria: Adults (18–70), active AS (ASDAS ≥ 2.1), history of latent TB (T-SPOT positive) or malignancy (resected thyroid/lung cancer), and no prior use of biologics/JAK inhibitors/MTX within 6 months.
• Groups:
  • Observation Group (n=30): Received Iguratimod (25mg BID) + Yunke Injection (IV daily) + NSAIDs (as needed).
  • Control Group (n=18): Received Iguratimod (25mg BID) + NSAIDs (as needed).
• Follow-up Duration: 24 months.

Key Metrics:

• Primary Efficacy: Changes in ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score) and BASFI (Bath Ankylosing Spondylitis Functional Index).
• Secondary Efficacy: Inflammatory markers (CRP, ESR), radiographic progression (mSASSS score), and total NSAID dosage.
• Safety: Adverse Events (AEs), specifically focusing on TB reactivation, tumor recurrence, hematological toxicity, and organ function.
• Statistical Analysis: Linear Mixed Models (LMM), t-tests, Mann-Whitney U tests, and Fisher's exact test (SPSS 26.0).

3. Key Contributions

• Novel Combination Therapy: This is one of the first studies to evaluate the synergistic effect of Iguratimod (immunomodulatory/bone-protective) and Yunke Injection (anti-inflammatory/anti-osteoclastic) specifically in the high-risk AS population (TB/Cancer history).
• Mechanistic Insight: The paper proposes a pharmacological synergy where Yunke Injection neutralizes free radicals and inhibits osteoclasts, while Iguratimod modulates cytokine release and bone metabolism pathways (Wnt/β-catenin, TLR4/NF-κB).
• Safety Profile for Contraindicated Groups: It provides evidence that this combination does not trigger TB reactivation or tumor recurrence, addressing a critical unmet need in rheumatology.

4. Results

Efficacy:

• Disease Activity (ASDAS): Both groups improved significantly. The Observation Group achieved a mean ASDAS of 1.62 (Low Disease Activity) vs. 1.72 in the Control Group. While the absolute difference was small, the trend favored the combination.
• Functional Index (BASFI): The Observation Group showed significantly greater improvement (1.69) compared to the Control Group (2.10) (P < 0.001).
• Inflammatory Markers: The Observation Group had significantly lower post-treatment CRP (6.29 vs. 13.92 mg/L, P < 0.001) and ESR (16.07 vs. 20.72 mm/h, P = 0.013) compared to the control group.
• Radiographic Progression (mSASSS): Both groups showed changes, but the Observation Group demonstrated a significantly greater reduction in progression (mean difference Δ=0.36, P < 0.001), suggesting better inhibition of spinal ankylosis.
• NSAID Reduction: The Observation Group required significantly less NSAID dosage over 24 months (128.6g vs. 210.7g, P < 0.001), indicating better pain control without heavy reliance on NSAIDs.

Safety:

• Adverse Events: No cases of TB reactivation, new malignancies, or tumor recurrence were observed in either group.
• Liver Function: Mild, transient elevations in transaminases occurred in both groups (2 patients each), managed with silybin capsules without discontinuing the study drugs.
• No Severe Events: No severe opportunistic infections, herpes zoster, hematological toxicity, or cardiovascular events were reported.

5. Significance and Conclusion

Clinical Implications:
The study concludes that the combination of Iguratimod and Yunke Injection is a safe and effective alternative for AS patients who cannot use biologics or JAK inhibitors. It offers:

1. Superior Functional Improvement: Better BASFI scores and reduced NSAID dependency.
2. Radiographic Protection: Slower progression of spinal fusion compared to Iguratimod monotherapy.
3. High Safety Margin: Crucially, it does not exacerbate tuberculosis or malignancy risks, making it a viable option for "high-risk" populations often excluded from standard advanced therapies.

Limitations:
The study acknowledges its retrospective nature, small sample size (n=48), and potential selection bias. The authors recommend future prospective, randomized controlled trials with larger cohorts to validate these findings.

Final Verdict: This combination therapy provides a novel, synergistic treatment strategy that balances efficacy with safety, specifically tailored for AS patients with comorbidities that preclude the use of standard biologic agents.