Anemia in Ankylosing Spondylitis: Evidence and Management
Anemia occurs in approximately 15-29% of patients with ankylosing spondylitis and is predominantly anemia of chronic disease (ACD), which improves significantly with anti-TNF therapy that controls the underlying inflammation. 1, 2
Prevalence and Types of Anemia in AS
The anemia spectrum in AS patients consists of three main types:
- Anemia of chronic disease (ACD) represents 44.1% of cases 1
- Combined ACD with iron deficiency accounts for 29.4% 1
- Iron deficiency anemia (IDA) alone comprises 23.5% 1
The severity of anemia directly correlates with inflammatory disease activity, as measured by BASDAI, ASDAS, CRP, and IL-6 levels 1. Hepcidin, the key regulator of iron metabolism, is elevated in 25% of AS patients and is highest in those with ACD, making it a useful diagnostic marker for differentiating anemia types 3.
Management Approach: Treat the Underlying Inflammation First
Primary Strategy: Control AS Disease Activity
The most effective treatment for anemia in AS is aggressive control of the underlying inflammatory disease, not iron supplementation alone. 2, 4
- NSAIDs remain first-line therapy for active AS with pain and stiffness 5, 6
- For patients with gastrointestinal risk factors, use non-selective NSAIDs plus a proton pump inhibitor, or selective COX-2 inhibitors 5, 7
- Physical therapy and regular exercise are mandatory, not optional components of treatment 5, 6, 7
Anti-TNF Therapy for Persistent Disease Activity
When disease activity remains high despite NSAIDs (BASDAI ≥4), anti-TNF therapy should be initiated, which simultaneously treats both the AS and the anemia. 5, 7
The evidence for anti-TNF therapy improving anemia is compelling:
- 81% of anemic AS patients achieved resolution of anemia after 6 months of anti-TNF therapy 2
- 70.3% of infliximab-treated patients normalized hemoglobin levels versus only 27.3% with placebo 4
- Mean hemoglobin increased by 0.7 gm/dl with infliximab versus a decrease of 0.3 gm/dl with placebo 4
- Hemoglobin improvement was independently associated with improvements in physical function (BASFI) and fatigue 4
Patients with elevated CRP or IL-6 at baseline show greater hemoglobin improvement with anti-TNF therapy, confirming that inflammation drives the anemia 4.
Regarding PSA (Prostate-Specific Antigen)
If the question refers to elevated PSA levels in a male AS patient, this represents a separate clinical issue requiring urological evaluation and does not alter the management of AS-related anemia. The anemia management remains focused on controlling inflammatory disease activity as outlined above. However, if prostate cancer is diagnosed, this would influence the choice of anti-TNF agent and require coordination with oncology 5.
Diagnostic Workup for Anemia in AS
When anemia is identified, obtain:
- Complete blood count with indices to assess severity and type 1
- Iron studies (serum iron, ferritin, transferrin) to differentiate ACD from IDA 1, 2
- Inflammatory markers (ESR, CRP, IL-6) to assess disease activity 1, 3
- Hepcidin levels can help differentiate ACD (elevated) from pure IDA (low), though this is not routinely available 3
Common Pitfalls to Avoid
- Do not treat with iron supplementation alone in patients with ACD or combined ACD/IDA without addressing the underlying inflammation, as iron absorption is impaired by elevated hepcidin 3
- Do not delay anti-TNF therapy in patients with persistently high disease activity (BASDAI ≥4) despite NSAIDs, as this perpetuates both the inflammatory disease and the anemia 5, 7, 2
- Do not use systemic corticosteroids for axial AS disease, as there is no evidence supporting efficacy and they carry significant side effects 5
- Do not ignore the multisystem nature of AS—coordinate care with other specialists for extra-articular manifestations including cardiovascular risk, which is also increased by chronic inflammation 5, 8
Monitoring Response
After initiating or escalating therapy: