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Anaemia to predict radiographic progression in rheumatoid arthritis
  1. Hanna W van Steenbergen,
  2. Jessica A B van Nies,
  3. Annette H M van der Helm-van Mil
  1. Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Hanna W van Steenbergen, Department of Rheumatology, Leiden University Medical Center, C1-R-046, Albinusdreef 2, P.O. Box 9600, RC Leiden 2300, The Netherlands; h.w.van_steenbergen{at}

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The severity of rheumatoid arthritis (RA) is highly variable between patients and currently known risk factors explain only part of this variance.1 Much research is dedicated to identify additional new risk factors. Such factors may shed light on the processes underlying progression of RA and many risk factors together may enable risk stratification and individualised treatment of RA.

With interest we read the study by Möller et al,2 showing that patients with RA with anaemia have more severe radiological progression. Although anaemia in RA is generally considered to be a consequence of chronic inflammation, this recent study based on patients with RA included in the Swiss SCQM-database- observed that the association between anaemia and joint damage was independent of the association between disease activity (measured with the Disease Activity Score including the 28-swollen joint count and erythrocyte sedimentation rate (DAS28ESR) and clinical Disease Activity Index (cDAI)) and joint damage. This led to the presumptions that anaemia in RA captures disease processes that are unmeasured by established disease activity markers (eg, subclinical inflammation) and that evaluation of the haemoglobin level may help to identify patients with rapid radiological progression.

Since in science replication of findings is relevant to ascertain the validity, we evaluated the association between anaemia at first presentation and disease severity over 7 years in 676 patients with early RA included in the Leiden Early Arthritis Clinic.1 Two outcome measures were studied. First, radiological progression; 3502 sets of hand and feet radiographs were made with yearly intervals and scored according to the Sharp-van der Heijde method by one reader (ICC 0.91).3 Second, disease persistency was assessed by evaluating its counterpart, achieving disease-modifying antirheumatic drugs (DMARD)-free sustained remission.4 Analyses were done using multivariate normal regression analysis and Cox regression.5 All analyses were adjusted for age, gender and treatment strategy.1 The haemoglobin level was determined at first presentation. WHO definitions for the presence and severity of anaemia were used.6

Of the patients with RA, 24.1% had anaemia at first presentation. These patients were older and had a higher swollen joint count (SJC), erythrocyte sedimentation rate (ESR) and C reactive protein (table 1). Patients with anaemia had more severe joint damage progression (β=1.03, p=0.012, indicating a 1.03 higher rate of joint destruction per year, which equals 1.037=23% more joint damage after 7 years). Similar to Möller et al, we also adjusted for ESR, SJC and rheumatoid factor (RF); this did not affect the association (β=1.03, p=0.040) (figure 1A). When evaluating the three haemoglobin categories a ‘dose-dependent’ effect was observed (β=1.03, p=0.002). Also this association was significant after adjusting for ESR, SJC and RF (β=1.02, p=0.032) (figure 1B). All analyses remained significant when the C reactive protein was included as covariate instead of the ESR (data not shown).7 Patients with anaemia tended to achieve DMARD-free remission less often than patients without anaemia (HR 0.57, 95% CI 0.34 to 0.95, p=0.031), also after adjusting for ESR, SJC and RF (HR 0.59, 95% CI 0.34 to 1.02, p=0.056) (figure 1C).

Table 1

Characteristics of patients with RA per haemoglobin category

Figure 1

Joint destruction (Sharp-van der Heijde scores (SHS)) and DMARD-free sustained remission curves over 7 years follow-up in patients with rheumatoid arthritis (RA), categorised according to the presence (A, C) or severity (B) of anaemia. (A, B) Presented are the median (by the multivariate normal regression model predicted) SHS during 7 years of follow-up of 676 patients with RA, categorised according to the presence (A) or severity (B) of anaemia. Patients with anaemia have a 1.03-fold radiographic progression rate compared with patients without anaemia, this is equal to a 1.23 higher rate of joint destruction over 7 years, which is similar to a 23% increase in rate of joint destruction. (C) Presented is the percentage of patients that achieved DMARD-free sustained remission curves during 7 years of follow-up of 669 patients with RA, categorised according to the presence/absence of anaemia (data on DMARD-free sustained remission were missing in seven patients). The analyses on DMARD-free sustained remission were not performed for the three haemoglobin categories because of low number of events in the moderate anaemia group. In all three figures, the analyses were adjusted for age, gender, treatment, erythrocyte sedimentation rate, rheumatoid factor and swollen joint count.

Analysis on this population-based inception cohort revealed that within RA anaemia is independently associated with radiographic progression. As clinical inflammation in RA may predominantly affect the feet,8 we evaluated a 66-SJC that—in contrast to the DAS28ESR and cDAI used by Möller et al—included the MTP joints. Nonetheless, we also observed that anaemia independently predicted disease severity. This may indicate that anaemia indeed reflects subclinical inflammation. Future studies are required to unravel this association.


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  • Contributors HvS and JvN acquired and analysed the data. HvS, JvN and AvdHvM interpreted the data and drafted the article.

  • Funding This work was supported by a Vidi-grant of the Netherlands Organisation for Scientific Research.

  • Competing interests None.

  • Ethics approval Ethics committee of the participating centre.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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