ObjectiveTo investigate whether antidrug antibodies and/or drug non‐trough levels predict the long‐term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.MethodsA total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme‐linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non‐trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.ResultsAmong patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.ConclusionPharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months.

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INTRODUCTION Anaemia is common in rheumatoid arthritis (RA). Clinicians may focus on rheumatological issues and assume anaemia of chronic disease (ACD). This study challenged this assumption and investigated the causes of anaemia in a large cohort of RA patients to assess its implications. METHODS The hospital where the study was conducted monitors regular full blood count and erythrocyte sedimentation rate (ESR) monthly in all RA patients on disease modifying drugs to assess efficacy and safety. A computerised system identifies and records abnormal results. The database for 2009 was interrogated to find all patients with two consecutive haemoglobin values <11 g/dl. Using a proforma, patients were defined as having iron deficiency anaemia (IDA), ACD, macrocytic anaemia (MCA) or another cause. All results of further tests investigating the anaemia were recorded. RESULTS Among 2000 RA patients on the system, 199 (10%) were identified as having anaemia over a year. Of these, 90 had IDA, 78 had ACD, 25 had MCA, and 6 had postoperative anaemia. Among 90 patients with IDA, investigations were performed in 53, with 23 normal. An explanation for IDA was found in 30: gastrointestinal bleeding in 25, gynaecological blood loss in 3, and urinary bleeding in 2. Among 78 patients with ACD, response to intensification of RA treatment occurred in 45, but erythropoietin therapy was required in 9. Within the 25 patients with MCA, 12 had unrecognised vitamin B(12) deficiency, 4 drug induced changes, 3 myeloid malignancy, 2 hypothyroidism, and 2 alcoholism. CONCLUSIONS Anaemia in RA is common, multifactorial, and potentially both serious and correctable. Established malignancy was present in 10 patients and premalignancy in a further 10 (10% of total). Treatable causes were commonly identified. Clinicians need to investigate the nature and cause of persistent anaemia, and must not assume it to be simply ACD without evidence.

-Morbidity and mortality from pneumonia is increased in patients with rheumatoid arthritis. Factors contributing to this have been recently identified and a number of recommendations have been implemented in an attempt to reverse this trend. The present paper shows that these measures have combined to produce a fourfold reduction in both admissions and case fatality rates. In the study population, immunisation rates against influenza and pneumococcus have improved to 86% and 65%, oral steroid consumption has halved and disease modifying drugs were usually appropriately suspended during acute infection. These measures may now merit more widespread adoption.

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interest. Bac...