Infection Risks of Biologics and Targeted Drugs in Spondyloarthritis: What a Meta-Analysis Reveals

If you or someone you know lives with spondyloarthritis (SpA)—a group of chronic inflammatory conditions that primarily affect the spine, joints, or entheses (the places where tendons/ligaments attach to bone)—you’ve likely heard of biologics. These drugs are game-changers for many people with SpA who don’t respond to first-line treatments like non-steroidal anti-inflammatory drugs (NSAIDs) or conventional disease-modifying anti-rheumatic drugs (csDMARDs). But a critical question lingers: Do biologics increase the risk of infections? A 2022 meta-analysis of 62 randomized controlled trials (RCTs) offers clear answers—and important takeaways for patients and doctors.

What Is Spondyloarthritis?

SpA isn’t a single disease; it’s a family of conditions with overlapping symptoms. The two main subtypes are:

Axial SpA: Affects the spine and pelvis (e.g., ankylosing spondylitis, non-radiographic axial SpA).
Peripheral SpA: Affects joints like knees, ankles, or hands, often linked to psoriasis, inflammatory bowel disease, or reactive arthritis.

For most people, NSAIDs (e.g., ibuprofen) or csDMARDs (e.g., methotrexate) reduce pain and slow joint damage. But up to 40% of SpA patients don’t get relief from these drugs—or can’t tolerate their side effects. That’s where biologics and small-molecule targeted drugs come in: They block specific proteins (like tumor necrosis factor [TNF]-α or interleukin [IL]-17) that drive inflammation in SpA, offering relief when other treatments fail.

The Study: What We Looked At

Researchers from the Chinese PLA General Hospital and Beijing Jishuitan Hospital analyzed data from 62 RCTs involving 19,411 SpA patients. RCTs are the gold standard for medical research because they randomly assign participants to either a biologic/targeted drug or a placebo (dummy drug), minimizing bias. The goal? To compare infection rates between the two groups.

The team focused on all infections, serious infections (e.g., pneumonia, sepsis), and specific infection types (e.g., upper respiratory tract infections [URTIs], Candida yeast infections, herpes zoster/shingles). They also split results by drug class (e.g., TNF-α inhibitors, IL-17 inhibitors, Janus kinase [JAK] inhibitors) and SpA subtype (axial vs. peripheral) to see if risks varied.

Key Findings: Who Is at Risk?

The results paint a clear picture: Biologics and targeted drugs do increase infection risk—but the type and severity depend on the drug and SpA subtype. Here’s what the data showed:

Overall Risks

Any infection: 16% higher risk in biologic users vs. placebo.
Serious infections: 65% higher risk (e.g., 2.6% of biologic users vs. 1.6% of placebo users developed serious infections).
Common infections: URTIs (17% higher risk), nasopharyngitis (25% higher risk), and Candida infections (2.6x higher risk) were all more likely in biologic users.

Drug-Specific Risks

IL-17 inhibitors: These drugs block IL-17, a cytokine that helps the body fight bacteria and fungi. For patients with peripheral SpA, IL-17 inhibitors tripled the risk of serious infections; for axial SpA, the risk doubled. Candida infections were also 2.5x more likely in peripheral SpA patients on IL-17 inhibitors.
TNF-α inhibitors: The most widely used biologics, TNF-α inhibitors increased common infections (e.g., URTIs, nasopharyngitis) in axial SpA but didn’t raise serious infection risk—consistent with earlier studies.
JAK inhibitors: A type of small-molecule drug, JAK inhibitors doubled the risk of herpes zoster (shingles) in patients with peripheral SpA.

Why These Risks Happen

To understand the link between biologics and infections, you need to know what these drugs do—and what they block.

IL-17 inhibitors: IL-17 is a key player in the immune system’s response to extracellular pathogens (e.g., bacteria, fungi). It recruits neutrophils (a type of white blood cell) to infection sites and stimulates proteins that fight invaders. Blocking IL-17 means your body is less prepared to fend off these microbes.
JAK inhibitors: JAK pathways help immune cells like natural killer (NK) cells fight viruses—including varicella-zoster, the virus that causes shingles. JAK inhibitors reduce NK cell activity, making reactivation of the virus more likely.
TNF-α inhibitors: TNF-α drives inflammation in SpA, but it also helps regulate the immune system. Blocking it slightly increases the risk of mild infections (like colds) but doesn’t compromise the body’s ability to fight serious threats—explaining why serious infection risk didn’t rise.

Important Limitations

The study isn’t perfect. Here are three key caveats:

Short follow-up: Most RCTs only tracked patients for 12–30 weeks. We don’t know about long-term infection risks (e.g., 1+ years of treatment).
Varying infection definitions: Not all studies used the same criteria for “infection,” which could skew results.
Confounding drugs: Many patients were on csDMARDs or steroids—drugs that also increase infection risk. The researchers couldn’t fully separate these effects from biologics.

What This Means for Patients and Doctors

These findings don’t mean biologics are “dangerous”—they’re life-changing for many people with SpA. But they do highlight the need for balanced decision-making:

For doctors: When prescribing biologics, weigh the drug’s benefits (e.g., reduced pain, slower joint damage) against its infection risks. For example, an IL-17 inhibitor might be the best option for a patient with severe axial SpA who failed TNF-α inhibitors—but the doctor should monitor for serious infections.
For patients: If you’re on biologics, watch for signs of infection (fever, persistent cough, yeast infections, or shingles rash) and report them to your doctor immediately. Don’t stop taking your medication without talking to your care team—untreated SpA can lead to permanent disability.

The Bottom Line

Biologics and targeted drugs are indispensable tools for treating SpA—but they’re not risk-free. This meta-analysis gives doctors and patients the data they need to make informed choices: IL-17 inhibitors may be powerful, but they carry serious infection risks; JAK inhibitors require vigilance for shingles; and TNF-α inhibitors are generally safe for mild infections.

As research evolves—especially long-term studies and real-world data—we’ll learn more about how to minimize these risks. For now, the takeaway is clear: Biologics work—but infection prevention and monitoring are non-negotiable.

This analysis was published in the Chinese Medical Journal in 2022 by Lidong Hu, Siliang Man, and colleagues from the Department of Rheumatology and Immunology at the Chinese PLA General Hospital and Beijing Jishuitan Hospital.

doi: https://doi.org/10.1097/CM9.0000000000001928

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