Pintip Ngamjanyaporn

Efficacy and Adverse Events of Mycophenolate Mofetil Versus Cyclophosphamide for Induction Therapy of Lupus Nephritis Systematic Review and Meta-Analysis

We performed a systematic review and meta-analysis of randomized controlled trials to compare complete remission and adverse events (that is, infection, leukopenia, and gastrointestinal [GI] symptoms) between mycophenolate mofetil (MMF) and cyclophosphamide (CYC) for the treatment of lupus nephritis (LN). We identified trials from MEDLINE using the PubMed and Ovid search engines, and from The Cochrane Central Register of Randomized Controlled Trials. Eligible studies were randomized controlled trials comparing MMF with CYC with 1 of following outcomes: complete remission, complete/partial remission, infection, leukopenia, GI symptoms, serum creatinine, 24-hour urine protein, and urine albumin. Data were independently extracted by 2 reviewers. Five trials with a total of 638 patients were eligible for review. While the MMF group tended to achieve complete remission more frequently than the CYC group, this was not significant (pooled risk ratio [RR], 1.60; 95% confidence interval [CI], 0.87-2.93). Pooling based on the 4 homogeneous trials yielded similar results-that is, no benefit of MMF compared with CYC groups (RR, 1.15; 95% CI, 0.74-1.77). The complete or partial remission rates were also not different (pooled RR, 1.21; 95% CI, 0.97-1.48) among the groups. The adverse events (infection, renal function, and GI symptoms) were not significantly different, except for leukopenia, which was lower in the MMF group. In summary, patients treated with MMF and CYC had similar remission rates, but the MMF group had less frequent leukopenia than the CYC group. Further large-scale trials are needed to confirm these results. Abbreviations: CI = confidence interval, CYC = cyclophosphamide, df = degree of freedom, GI = gastrointestinal, LN = lupus nephritis, MMF = mycophenolate mofetil, NNH = number needed to harm, NNT = number needed to treat, PRISMA = preferred reporting items for systematic reviews and meta-analyses, RR = risk ratio, SE = standard error, SLE = systemic lupus erythematosus, SMD = standardized mean difference, WHO = World Health Organization.

Primary Prophylaxis for Pneumocystis jirovecii Pneumonia in Patients with Connective Tissue Diseases

OBJECTIVES The aim of our study was to examine the primary prophylactic effect of sulfamethoxazole/trimethoprim single strength (SMZ/TM SS) against Pneumocystis jirovecii pneumonia (PCP) in connective tissue disease (CTD) patients with immune dysfunction induced by the long-term use of prednisolone. Prevalence of adverse drug reactions (ADRs) to sulfonamide in these patients was the secondary outcome. METHODS This was a retrospective cohort study. Medical records of CTD patients who were treated with prednisolone ≥20 mg per day or equivalent doses of corticosteroid for more than 2 weeks and were followed for at least 12 weeks after receiving this dosage of corticosteroids at the Rheumatology clinic of Ramathibodi Hospital between October 2006 and September 2007 were reviewed. Information regarding clinical status, laboratory features, and clinical course of the enrolled subjects was recorded. RESULTS There were 138 episodes of PCP risk in 132 CTD patients; 59 episodes received SMZ/TM SS, while 79 episodes did not. All 6 PCP cases developed in patients without prophylaxis with an overall incidence of 4.3%. The incidence of PCP between the 2 groups was significantly different (P = 0.038). Absolute risk reduction and relative risk reduction were 7.3% and 100%, respectively. All ADR developed in 5 systemic lupus erythematosus patients (8.5%): 4 had drug rashes and 1 had mild hepatitis. There was no correlation between the use of, or allergic reactions to, SMZ/TM and lupus flare. CONCLUSIONS Sulfamethoxazole/trimethoprim single strength can be used effectively as a primary prophylaxis against PCP in high-risk CTD patients. Only mild ADR developed at this dosage. Further evaluations in larger groups of CTD patients are warranted.

Real-life effectiveness of budesonide/formoterol maintenance and reliever therapy in asthma patients across Asia: SMARTASIA study

BackgroundThe use of budesonide/formoterol in a single inhaler for both maintenance and reliever therapy is a recommended option for treatment of persistent asthma not responding well to inhaled corticosteroid (ICS) alone.MethodsThis was a multi-centre open-label study on patients whose asthma condition remained inadequately controlled by various asthma treatments other than budesonide/formoterol. After a 2-week run-in period, eligible patients underwent a 12-week treatment period with budesonide/formoterol (Symbicort SMART®, 160/4.5 μg) twice daily plus as needed. Patient’s asthma control and quality of life were assessed using the 5-item Asthma Control Questionnaire (ACQ-5) and the standardized Asthma Quality of Life Questionnaire (AQLQ-S), respectively.ResultsA total of 862 eligible asthma patients who have had asthma for a mean duration of 10.73 ± 12.03 years entered a 12-week treatment with budesonide/formoterol maintenance and reliever therapy. During treatment, ACQ-5 score improved significantly by 0.58 ± 0.93 (95% CI, 0.51 to 0.64, P < 0.0001) from the baseline level of 1.62 ± 1.00. AQLQ(S) score improved by 0.70 ± 0.89 (95% CI, 0.64 to 0.76, P < 0.0001) from baseline. Asthma symptom score was also reduced significantly (P < 0.0001); between run-in and treatment periods, night- and day-time symptom scores were reduced by 0.32 ± 0.54 (95% CI, 0.28 to 0.35) and 0.30 ± 0.52 (95% CI, 0.27 to 0.34), respectively. The percentage of nights with awakenings due to asthma symptoms was reduced by 11.09 ± 26.13% (95% CI, 9.34 to 12.85%), while the percentage of asthma-control and symptom-free days increased by 20.90 ± 34.40% (95% CI, 18.59 to 23.21%) and 23.89 ± 34.62% (95% CI, 21.56 to 26.21%), respectively (P < 0.0001). Together with the improvement in asthma control, the number of night- and day-time inhalations of as-needed reliever medication decreased by 0.30 ± 0.82 (95% CI, 0.24 to 0.35) inhalations and 0.30 ± 0.97 (95% CI, 0.23 to 0.36) inhalations, respectively (P < 0.0001). No unexpected adverse events were reported.ConclusionDuring treatment of inadequately controlled asthmatic patients with budesonide/formoterol maintenance and reliever therapy, significant improvement in patients’ asthma control and reductions in asthma symptoms and as-needed medication use was observed. Patients’ quality of life was improved and the treatment was well tolerated.Trial registrationClinicalTrial.gov: (NCT00939341)

Selective IgM deficiency in an adult presenting with Streptococcus pneumoniae septic arthritis

Septic arthritis caused by Streptococcus pneumoniae is uncommon. Most of the patients who have invasive pneumococcal infection have underlying diseases associated with impaired immune function. We report a case of polyarticular pneumococcal septic arthritis in a previously healthy adult as the first manifestation of selective immunoglobulin (Ig)M deficiency. The patient had no evidence of autoimmune disease or malignancy. Serum IgG, IgA, and complement levels were normal. Numbers of lymphocyte subsets were in normal range except that of CD4+ cells, which was slightly low. Invasive pneumococcal disease in a healthy adult should lead to further investigation for underlying diseases including primary immunodeficiencies.

Clinicians approaches to management of background treatment in patients with SLE in clinical remission: results of an international observational survey

Background The definition of remission in systemic lupus erythematosus (SLE) remains unclear, especially how background treatment should be interpreted. Objective To determine preferences of clinicians in treatment of patients in clinical remission from SLE and to assess how previous severity, duration of remission and serology influence changes in treatment. Methods We undertook an internet-based survey of clinicians managing patients with SLE. Case scenarios were constructed to reflect different remission states, previous organ involvement, serological abnormalities, duration of remission and current treatment (hydroxychloroquine (HCQ), steroids and/or immunosuppressive (ISS) agents). Results 130 clinicians from 30 countries were surveyed. The median (range) duration of practice and number of patients with SLE seen each month was 13 (2–42) years and 30 (2–200), respectively. Management decisions in all scenarios varied with greater caution in treatment reduction with shorter duration of remission, extent of serological abnormalities and previous disease severity. Even with mild disease, normal serology and a 5-year clinical remission, 113 (86.9%) clinicians continue to prescribe HCQ. Persistent abnormal serology in any scenario led to a reluctance to reduce or discontinue medications. Prescribing in remission, particularly of steroids and HCQ, varied significantly according to geographical location. Conclusions Clinicians preferences in withdrawing or reducing treatment in patients with SLE in clinical remission vary considerably. Serological abnormalities, previous disease severity and duration of remission all influence the decision to reduce treatment. It is unusual for clinicians to stop HCQ even after prolonged periods of clinical remission. Any definition(s) of remission needs to take into consideration such evidence on how maintenance treatments are managed.

Angiotensin‐converting enzyme gene polymorphism in Thai patients with systemic lupus erythematosus

To determine the association between angiotensin‐converting enzyme (ACE) I/D polymorphism and the presence of systemic lupus erythematosus (SLE) disease and lupus nephritis (LN), including the association with disease severity in a Thai population.

The model of circulating immune complexes and interleukin-6 improves the prediction of disease activity in systemic lupus erythematosus

Systemic Lupus Erythematosus (SLE) is an autoimmune disease resulting in autoantibody production, immune complex deposition, and complement activation. The standard biomarkers such as anti-dsDNA and complements (C3 and C4) do not always correlate with active clinical SLE. The heterogeneity of SLE patients may require additional biomarkers to designate disease activity. Ninety SLE patients participated in this study. Evaluation of disease activity was achieved with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and modified SLEDAI-2K. The measured serum biomarkers were anti-dsDNA, C3, C4, ESR, interleukin-6 (IL-6), and circulating immune complexes (CIC). IL-6, ESR and CIC significantly increased in active clinical SLE. Complement, anti-dsDNA, ESR and CIC correlated with SLEDAI-2K while only anti-dsDNA, CIC, ESR and IL-6 correlated with modified SLEDAI-2K. A combination of biomarkers gave a higher odds ratio (OR) than any single biomarker. A combination of IL-6 or CIC exhibited the highest OR (OR = 7.27, 95%CI (1.99–26.63), p = 0.003) while either complement or anti-dsDNA showed a moderate odds ratio (OR = 3.14, 95%CI (1.16–8.48), p = 0.024) of predicting clinical active SLE. The combination of CIC and IL-6 strongly predicts active clinical SLE. CIC and IL-6 can be used in addition to standard biomarkers to determine SLE activity.

Cytokine profiling in active and quiescent SLE reveals distinct patient subpopulations

BackgroundPatients with SLE display marked clinical and immunlogical heterogeneity. The purpose of the study was to investigate patterns of serum cytokines in patients with active and stable systemic lupus erythematosus (SLE) and to determine how they relate to clinical phenotype.MethodsSerum levels of 10 cytokines were measured retrospectively in a cohort of patients with SLE and in healthy controls using a high-sensitivity multiplex bead array. Disease activity was determined using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and British Isles Lupus Assessment Group (BILAG-2004) indices. Logistic regression models were used to determine the association between cytokine levels and active SLE. Principal component analysis (PCA) and cluster analysis was then used to identify subgroups of patients on the basis of cytokine levels.ResultsSerum chemokine (C-X-C motif) ligand 10 (CXCL10) and CXCL13 were significantly higher in patients with SLE compared to healthy controls. Two cytokines (pentraxin-related protein (PTX3) and CXCL10) were significantly higher in patients with active disease after adjustment for potential confounding factors. Measurement of four cytokines (CXCL10, IL-10, IL-21 and PTX3) significantly improved the performance of a model to identify patients with clinically active disease. Cluster analysis revealed that the patients formed 3 distinct groups, characterised by higher levels of interferon alpha (IFNα) and B lymphocyte stimulator (BLyS) (group 1), increased CXCL10 and CXCL13 (group 2) or low levels of cytokines (group 3). Group 2 had significantly lower serum complement and higher anti-double-stranded DNA antibodies and increased prevalence of inflammatory arthritis.ConclusionsMultiplex analysis has identified a serum cytokine signature for active SLE. Within the SLE population distinct cytokine subgroups were identified, with differing clinical and immunological phenotypes that appeared stable over time. Assessment of cytokine profiles may reveal unique insights into disease heterogeneity.

323 Comparison of circulating immune complex and interleukin-6 with standard biomarkers to determine sle disease activity

Background and aims Systemic Lupus Erythematosus (SLE) is an autoimmune disease involving in autoantibody production, immune complex deposition and complement activation. When the disease is active, the sequel can be devastated if inappropriately treated.The outcome of SLE patients can improve if sensitive biomarkers can identify the recent flare and lead the patients to receive the correct treatment in time. This study aimed to investigate whether serum levels of IL-6 and circulating immune complex (CIC) correlated with SLE disease activity and compared with anti-dsDNA and complement. Methods Ninety SLE patients followed up at Ramathibodi Hospital in 2015 were enrolled. The evaluation of disease activity achieved by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The active disease defined if the scores were more than one. Serum IL-6 and CIC tested by ELISA. Results The level of serum IL-6 and CIC in SLE patients with active disease activity was significantly higher than the inactive disease [5.5 (1.6–99.30) pg/ml vs 3.6 (1.5–35.1) pg/ml, p=0.011 and10.12 (2–131.22) RU/ml vs 2.1 (2.0–101.37) RU/ml, p=0.011, respectively]. The correlation analysis between serum biomarkers and clinical SLEDAI demonstrated that biomarkers significantly correlated with SLE activity are CIC (R=0.331, p=0.001) and IL-6 (R=0.313, p=0.011). CIC had the most area under the curve in discriminating active SLE than IL-6, anti-dsDNA, C4 and C3 (AUC=0.698, 0.677, 0.634, 0.410 and 0.393 respectively) Conclusions Serum CIC and IL-6 significantly correlated with clinical SLEDAI, which is higher degree of correlation than anti-dsDNA, C4 and C3 levels. Our study suggested that CIC and IL-6 can be used as alternative biomarkers to determine SLE activity.