Dr. Ahmed Key points
- The study found that certain biologic and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) may raise the risk of cancer in patients with rheumatoid arthritis (RA).
- The drugs that were linked with a higher cancer risk included rituximab, abatacept, and JAK inhibitors (JAKis).
- The risk of cancer was more prevalent in patients who were starting rituximab, abatacept, and JAKis compared to those starting tumor necrosis factor inhibitors (TNFis).
- The high cancer risk was observed in the first 2 years after starting bDMARDs or tsDMARDs.
- The study was a prospective observational study using data from a large Spanish registry.
Rheumatoid arthritis is a chronic autoimmune condition that primarily affects the joints, leading to inflammation, pain, stiffness, and swelling; its prevalence ranges from 0.24 to 1% [ref].
Over time, it can lead to joint deformities and damage to surrounding tissues if it is left untreated. The immune system can mistakenly attack the synovium, the lining of the joints, which then causes thickening and the release of inflammatory chemicals that harm cartilage and bone.
RA can also reach other organs like the heart, lungs, and eyes, and this is why it is called a systemic disease. Symptoms often include morning stiffness, fatigue, and symmetrical joint involvement, with causes linked to genetic, hormonal, and environmental factors.
Antirheumatic drugs are medications employed to manage and treat rheumatoid arthritis by reducing inflammation, relieving pain, and slowing joint damage. They are categorized into nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs).
NSAIDs alleviate pain and swelling but do not prevent disease progression, while corticosteroids offer rapid relief by suppressing the immune system.
DMARDs, including methotrexate and newer biologic agents, target the underlying autoimmune process to limit joint destruction and preserve function. Early and aggressive treatment with these drugs is rather important for long-term outcomes in RA patients. However, some studies have suggested that these drugs may increase the risk of cancer.
A recent study published in JAMA Network Open found a higher cancer risk with rituximab, abatacept, and JAK inhibitors versus TNFis, likely due to channeling bias rather than the drugs themselves.
Methodology
This study analyzed data from the Merative Marketscan Research Databases, which include health records of millions of people with employer-sponsored health insurance across the United States of America.
These records provide detailed information about doctor visits, hospital stays, prescriptions, and procedures.
Since the data was already anonymized, researchers did not need patient consent or special approval from an ethics board. The study followed established guidelines for reporting observational research.
The authors focused on adults aged 18 to 64 with rheumatoid arthritis (RA) who started certain RA treatments between November 2012 and December 2021.
They excluded people over 65 (due to different insurance coverage) and those with specific other conditions like cancer, HIV, or organ transplants to ensure a consistent study group.
Patients had to have RA confirmed by two separate diagnoses and at least three months of follow-up. The study compared the effects of various treatments, including TNFis (like adalimumab and etanercept), IL-6 inhibitors, rituximab, and JAK inhibitors, to understand their safety and effectiveness.
Analysis and some limitations
The study analyzed the risk of incident cancer associated with different biologic and targeted synthetic disease-modifying antirheumatic drug (DMARD) treatments for rheumatoid arthritis (RA).
They used Cox proportional hazards regression models to calculate hazard ratios (HRs) for cancer risk, adjusting for potential confounders.
Tumor necrosis factor inhibitors (TNFis) served as the reference group. Propensity matching was also conducted to address confounding by indication.
The study found that rituximab and abatacept were associated with a really higher risk of cancer compared to TNFis, while JAK inhibitors (JAKis) showed a non-significant increase in risk.
IL-6 inhibitors had a similar risk to TNFis in the primary analysis but showed a significant increase in the propensity-matched analysis.
Here are some limitations:
- The study relied on historical data, which limits the ability to control for all variables and establish causality. Retrospective analyses are inherently observational and prone to biases.
- Important variables such as detailed disease severity, patient adherence to medication, and lifestyle factors (e.g., diet and physical activity) may not be well captured.
- The follow-up period of up to two years may not be sufficient to actually capture the long-term cancer risk associated with bDMARD or tsDMARD therapies, as cancer development can take years.
Conclusion
While antirheumatic drugs are crucial for managing rheumatoid arthritis, it is better to be aware of their potential side effects, which include an increased risk of certain cancers, particularly with some newer medications like rituximab, abatacept, and JAK inhibitors.
Likewise, you must weigh the potential benefits of these drugs against the risks, especially when considering long-term use. You need to have a proper consultation with your physician to discuss any and every concern and make sure you go through a safe and effective treatment.
If you have any concerns about your medication or potential side effects, do nott hesitate to discuss them with your doctor.
