Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

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 interes

Comparative performance of composite measures from two phase III clinical trials of ixekizumab in psoriatic arthritis

Background/objective The aim of this study was to evaluate relative performance of composite measures in psoriatic arthritis and assess the impact of structural damage and functional disability on outcomes during ixekizumab treatment. Methods Data from SPIRIT-P1 and SPIRIT-P2 were analysed to evaluate the effect of ixekizumab on achievement of low disease activity (LDA) and remission with the minimal disease activity (MDA) and very low disease activity (VLDA) composite, Disease Activity index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score, GRAppa Composite ScorE and modified Composite Psoriatic Disease Activity Index (mCPDAI). Performance was compared by quantifying residual symptom burden and the impact of structural damage and functional disability. Results Significantly more ixekizumab-treated patients achieved treatment targets at week 24 versus placebo assessed with all composites. More patients achieved targets assessed by mCPDAI and DAPSA than other composites. Residual disease activity was similar between composites, but residual high patient-reported outcomes (PROs) and functional disability were more frequent when assessed with mCPDAI and DAPSA. Achievement of treatment targets was reduced by high baseline levels of structural damage and functional disability. Conclusion Residual disease activity was similar in patients achieving treatment targets assessed with all composites, but residual high PROs and functional disability were more common when assessed with mCPDAI and DAPSA, most likely due to the absence/attenuated functional assessment in these composites. High baseline levels of structural damage and functional disability attenuated response rates with all composites, affecting MDA/VLDA most prominently; LDA may be the most appropriate target in these patients. Trial registration number NCT01695239

A Multi-Biomarker Disease Activity Score For Rheumatoid Arthritis Predicts Radiographic Damage In The BeSt Study

Pathophysiology and treatment of rheumatic disease

A Multibiomarker Disease Activity Score for Rheumatoid Arthritis Predicts Radiographic Joint Damage in the BeSt Study

Pathophysiology and treatment of rheumatic disease