Predictive Factors Of Clinical Response Research Articles

Predictors of Clinical Benefit with Intra-articular Hyaluronic Acid in Patients with Knee Osteoarthritis - A Narrative Review.

There is conflicting evidence regarding the efficacy of viscosupplementation with intra-articular hyaluronic acid injections in knee osteoarthritis. One possible explanation for the inconsistent findings on its efficacy is that only certain subpopulations of patients benefit from this therapy. The purpose of this narrative review is to succinctly summarize the existing data on the predictive factors of clinical response to intra-articular hyaluronic acid to identify the patient profile most likely to benefit from this therapy. For this narrative review, a PubMed search was conducted in January 2023, with no date limits, to identify publications reporting predictive factors of response to viscosupplementation using the following terms: hyaluronic acid OR viscosupplem* AND osteoarthritis AND knee AND predict*. Searches were limited to randomized controlled trials, systematic reviews and meta- analyses, or observational studies written in English. Other relevant references were identified by searching the references of retrieved articles. The disease severity was found to reliably predict response to intra-articular hyaluronic acid injections; patients with less severe disease consistently had a more robust therapeutic response than those with more severe disease. Other clinical variables such as level of baseline pain did not reliably predict response. Body mass index, and possibly age, may also be independent predictors of the response. A review of the existing literature suggests that patients with less severe clinical symptoms and radiological findings, who are younger, and with a lower or normal body mass index are the best candidates for intra-articular hyaluronic acid therapy.

Efficacy and predictive factors of clinical response to hyaluronic acid ＋ chondroitin sulfate bladder instillations for the treatment of BPS/IC

Aim of the study:To assess the efficacy of intravesical hyaluronic acid and chondroitin sulfate (HACS) instillations in treating patients with bladder pain syndrome/interstitial cystitis (BPS/IC), as well as to identify predictive factors for clinical response. Materials and methods:Patients diagnosed with BPS/IC and treated with Ialuril® (HACS) bladder instillations between January 2018 and August 2020 were included. Data collected included Visual Analog Scale (VAS) scores, number of pain episodes, 3-day frequency volume chart measurements (at baseline and last follow-up), Patient Global Impression of Improvement (PGI-I) questionnaire responses, age, history of urinary tract infections (UTIs), and endoscopic findings from cystoscopy with hydrodistension. Statistical analyses included Mann–Whitney’s non-parametric U-test and chi-square test with a 95% confidence interval (p ≤ 0.05) to identify predictive factors of treatment success. Results:A total of 104 patients were treated with a median follow-up of 29 months (IQR 14–40), predominantly female with a mean age of 60 ± 16 years. At the last follow-up, there was a median reduction of 1 point in the VAS score (IQR 1–1), whilst only 20% experienced a reduction of ≥2 points. A statistically significant correlation was observed in the reduction of days with pain per month before and after treatment (ΔDPV) (median reduction: 6 days, IQR 2–7, p < 0.001). No adverse events were reported during treatment. Regarding prognostic factors, three statistically significant correlations were found: between PGI-I success and age (p=0.050), between ΔVAS score and recurrent UTIs (p=0.044), and between ΔDPV and recurrent UTIs (p=0.04). Discussion:The study did not demonstrate any significant reduction of VAS score or diurnal and nocturnal voiding frequency after treatment, on the contrary it did show a reduction in the number of days with pain. Consequently, 88.3% of patients reported positive subjective improvement on the PGI-I questionnaire, and none discontinued treatment. Endoscopic findings did not appear to correlate with treatment response. Conclusions:Age and the presence of recurrent UTIs may influence the response to intravesical HACS therapy in terms of PGI-I, VAS score, and reduction in days with pain.

Intratumoral CD8+ T cells as a potential positive predictor of chemoimmunotherapy response in PD-L1-negative advanced gastric cancer patients: a retrospective cohort study.

BackgroundPrevious studies have shown that PD-L1-positive advanced gastric cancer (GC) patients could achieve clinical benefit after receiving immune checkpoint inhibitors (ICI) in initial or subsequent therapy. A number of prospective studies such as Keynote-158 have demonstrated that PD-L1-negative patients who tested as microsatellite instability-high (MSI-H) or tumor mutational burden-high (TMB-H) can benefit from ICIs. In the search for more biomarker for immunotherapy, some studies showed that patients with a specific characteristic to tumor microenvironment (TME) were associated with better prognosis. This study aimed to explore the association between the TME and immunotherapy in PD-L1 negative GC patients.MethodsThis study was a retrospective cohort study. Twenty-six CPS PD-L1 negative stage IV advanced GC patients treated with chemoimmunotherapy in Shenzhen Hospital of Peking University were retrospectively enrolled according to the inclusion criteria. Their clinical characteristics were assessed and recorded by independent clinicians. Follow-up data was conducted through the Internet or visit. Respond to treatment was evaluated by RECIST 1.1. The primary outcome was progression-free survival (PFS). The level of tumor-infiltrating lymphocytes (TILs) was measured by multiplex immunofluorescence (mIF) among these patients. Cox proportional hazards analysis was performed to analyzed the correlation between PFS and clinical characteristics including TILs.ResultsAmong 26 patients, 5 patients (19.2%) were on complete response (CR) and 9 patients (34.6%) were in partial response (PR), while 7 patients (26.9%) experienced stable disease (SD). Intratumoral CD8+ T cells were obviously increased in CPS PD-L1 negative patients who responded to chemoimmunotherapy, compared with patients who did not respond (P=0.011). And higher level of CD8+ TILs was demonstrated to associate with better PFS in CPS PD-L1-negative patients treated with chemoimmunotherapy (HR =23.70, 95% CI: 1.15–488.30, P=0.04).ConclusionsIntratumoral CD8+ TILs may be a potential positive predictive factor of clinical response for chemoimmunotherapy in PD-L1-negative advanced GC. However, the results need to be further confirmed in a cohort with more subjects due to a limited sample sizes in present study.

Efficacy and safety of endoscopic pyloric balloon dilation in patients with refractory gastroparesis.

There has been interest in the use of pyloric therapies for the treatment of refractory gastroparesis. However, data on endoscopic pyloric dilation are scarce. We aimed to assess the efficacy and safety of this procedure in refractory gastroparesis. We performed a retrospective analysis of 47 patients referred for refractory gastroparesis, confirmed by gastric emptying scintigraphy, and treated with endoscopic pyloric through-the-scope balloon dilation. The primary endpoint was the effectiveness of the procedure, evaluated with the Gastric Cardinal Symptom Index (GCSI) at 2 and 6months. A clinical response, defined by a 1.0 point decrease in the GCSI score, was observed in 25 patients at 2months (53%) and in 19 patients at 6months (40%). The mean GCSI score decreased significantly at 2 and 6months compared to the preoperative score (3.9 ± 0.87 vs 2.3 ± 1.37 and 3.9 ± 0.87 vs 2.9 ± 1.27, respectively; p < 0.0001). No complication was observed. Nine patients had a delayed relapse at 1year. A second dilation was performed for eight patients and it was effective in five of them (63%). The mean follow-up time of the patients was 27.0 ± 10.4months. At 2years, 15 patients still experienced improvement following this treatment (32%). No predictive factor of clinical response was identified. The efficacy of pyloric dilation is 53% at 2months, with sustained improvement in one third of patients at 2years. This treatment should be considered as an alternative option to pyloromyotomy.

The effect of anxiety, psychopathological symptoms and personality traits on response to treatment in male patients with anogenital warts: a prospective study.

In the era of precision medicine, identification of possible predictive factors of clinical response to treatment is fundamental. This need is particularly strong for anogenital warts (AGW), because there are several treatment modalities with different clearance and recurrence rates. However, data regarding the effect of mental health parameters on response to treatment in patients with AGW are lacking. The purpose of the present study was to evaluate the association between patients' mental health parameters and AGW treatment outcomes. This was a single-centre, prospective study that included newly diagnosed male patients with AGW. At their initial visit, all patients completed the State-Trait Anxiety Inventory (STAI), the Symptom Checklist-90-Revised (SCL-90-R) and the Eysenck Personality Questionnaire (EPQ) questionnaires, which evaluate anxiety, psychopathological manifestations and personality traits, respectively. All patients received cryotherapy until clearance of lesions and were followed up for 18months for detection of recurrences. The study included 167 male patients. The mean number of days for AGW clearance was 89±65. During the 18-month follow-up, 28% of participants showed a recurrence, after a mean number of 150±132days. No statistically significant association was detected between questionnaires scores and (a) time needed for AGW clearance, (b) time until 1st recurrence and (c) number of recurrences. If confirmed, our findings indicate that we may not need to modify our AGW treatment plan according to a patient's mental health profile.

Outcome and risk factor of immune-related adverse events and pneumonitis in patients with advanced or postoperative recurrent non-small cell lung cancer treated with immune checkpoint inhibitors.

BackgroundNon‐small cell lung cancer (NSCLC) patients with pre‐existing respiratory diseases have been excluded in clinical trials of immune checkpoint inhibitor (ICI) therapy, and it is unknown whether the same degree of response can be expected as that in patients without pre‐existing respiratory diseases and if they are associated with increased risk for various immune‐related adverse events (irAEs) and ICI pneumonitis. This study aimed to evaluate predictive factors of clinical response, prognostic factors, risk factors of irAEs, and ICI pneumonitis in NSCLC patients with or without pre‐existing respiratory diseases.MethodsWe conducted a retrospective study of 180 NSCLC patients who received ICI monotherapy of nivolumab, pembrolizumab, or atezolizumab from 1 January 2016 to 31 March 2019.ResultsA total of 119 patients had pre‐existing respiratory diseases, including 20 with pre‐existing idiopathic interstitial pneumonias (IIPs). A total of 85 patients experienced irAEs, of which ICI pneumonitis was the most frequent adverse event, occurring in 27 patients. Of the three patients who died from irAEs, all from ICI pneumonitis, two had pulmonary emphysema and one had pre‐existing IIP. In multivariate analyses, irAEs were associated with objective response rate (ORR) and favorable OS, and IIPs were associated with increased risk for ICI pneumonitis. However, IIPs were not associated with low ORR or poor OS.ConclusionsPre‐existing IIPs were a risk factor for ICI pneumonitis. However, this study showed that ICI therapy can be offered to patients with pre‐existing respiratory diseases with the expectation of the same degree of response as that in patients without pre‐existing respiratory diseases.Key pointsSignificant findings of the study: Pre‐existing IIPs were a risk factor for ICI pneumonitis, but objective response rate and prognosis of patients with IIPs were similar to those of other patients.What this study adds: In patients with pre‐existing IIPs, ICI pneumonitis should be noted. However, ICI therapy can be offered to patients with pre‐existing respiratory diseases with the expectation of the same degree of response as that in patients without pre‐existing respiratory diseases

Anti-carbamylated protein antibodies as a clinical response predictor in rheumatoid arthritis patients treated with abatacept.

Carbamylation is an irreversible post-translational modification of proteins. The presence of anti-carbamylated protein antibodies (anti-CarP) has been observed in rheumatoid arthritis (RA). This study was focused to verify whether anti-CarP antibodies can be used as a predictive factor of clinical response to abatacept (CTLA4-Ig) in RA patients. Sixty RA patients treated with abatacept were enrolled. A home-made ELISA for anti-CarP and a commercial anti-CCP3.1 kit for anti-citrullinated proteins antibodies (anti-CCP) were applied to determine serum levels every six months of therapy. Rheumatoid factor (RF) was also tested. Anti-CarP positive patients (n=18) were younger (p=0.01) and with a longer disease duration (p=0.05) when compared to anti-CarP negative patients (n=42) at baseline. Considering the entire cohort, a significant reduction of anti-CarP titre after twelve-months of treatment was shown (p<0.01). A significant reduction of Disease Activity Score (DAS) 28-C-reactive protein (CRP) in the first six months of therapy was found in the subgroup of anti-CarP positive patients in comparison with the negative ones (p=0.003). No significant results were found by dividing the cohort using the positivity to anti-CCP and/or RF. Earlier onset and a longer disease duration in anti-CarP positive patients might suggest they are specific risk factors for RA in this subgroup of patients. The correlation between the anti-CarP positivity at baseline and the reduction of disease activity during the first six months of treatment with abatacept allowed us to hypothesise that anti-CarP antibodies, but not anti-CCP and/or RF, could be used as a good clinical response predictor.

Predictive factors of clinical response to treatment with anti-TNF agents in ulcerative colitis: what have we learned from our patients?

inhibitors of tumor necrosis factor alpha (anti-TNFs) are effective drugs for the treatment of moderate-to-severe ulcerative colitis (UC). However, many patients do not respond or lose therapeutic response during follow-up. to analyze the determining factors of clinical response to anti-TNFs in UC. a multicenter retrospective study was performed in 79 patients with UC who started treatment with anti-TNFs between 2009 and 2015. The primary endpoint was clinical remission (pMayo index ≤ 1) at 12 months. Furthermore, remission and clinical response (final pMayo score ≤ 3) and corticoids discontinuation were assessed at three, six and 12 months. An analysis was performed to identify variables predictive of clinical response. at 12 months, remission and clinical response were seen in 59.2 % and 77.8 % of patients, respectively. Corticoids could be discontinued in 82.4 % of patients. At 12 months, corticoids discontinuation (< 3 months) (OR 0.06; 95 % CI: 0.01-0.24) and clinical response at six months (OR 0.008; 95 % CI: 0.001-0.053) were independent factors predictive of clinical remission. in patients with active UC on anti-TNFs, corticoid discontinuation within three months and clinical response at six months after treatment onset are predictive of clinical disease remission.

Indigo naturalis is effective even in treatment-refractory patients with ulcerative colitis: a post hoc analysis from the INDIGO study.

We recently reported the efficacy of indigo naturalis (IN) in patients with active ulcerative colitis (UC) in a randomized controlled trial (INDIGO study). However, few studies have been conducted to investigate whether IN is effective even in treatment-refractory cases, such as in those with steroid dependency and anti-TNF refractoriness. In the INDIGO study, 86 patients with active UC were randomly assigned to an IN group (0.5-2.0g daily) or placebo group. The rate of clinical response (CR), mucosal healing (MH), and change in fecal calprotectin (FCP) levels was compared between refractory [patients with steroid-dependent disease, previous use of anti-TNF-α, and concomitant use of immunomodulators (IM)] and non-refractory patients. We also analyzed factors predicting CR and MH at week 8. The rates of CR of IN group were significantly higher than placebo group, even in patients with steroid-dependent disease (p < 0.001), previous use of anti-TNF-α (p = 0.002), and concomitant use of IM (p = 0.013). The rates of MH in IN group were significantly higher than in placebo group in patients with steroid-dependent disease (p = 0.009). In the IN group, median FCP levels, at week 8, were significantly lower than baseline in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α (p < 0.001, respectively). Multivariate analysis indicated that the previous use of anti-TNF-α was not a predictive factor for CR and MH at week 8. In a sub-analysis of data from a randomized placebo-controlled trial, we found that IN may be useful even in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α.

Right carotid Doppler signal to optimize cardiac resynchronisation therapy implant procedure

Left-ventricular pre-ejection time (LVPET) varies according to cardiac homodynamic performance and is a predictive factor of clinical response to cardiac resynchronisation therapy (CRT) when > 140 ms. LVPET could then play a role in optimizing CRT implantation. However, its measurement requires the use of echocardiography in apical view, which is hardly compatible with device implantation environment. The objective of this study was to determine the relationship between LVPET measured conventionally from an apical view and time from beginning of QRS to beginning of Doppler signal flow (QWT) recorded at the right carotid. LVPET was measured using M5S probe and pulsed Doppler on aortic flow in apical view using echocardiography. QWT was measured using a Pedoff probe at the right carotid. These measurements were performed during spontaneous rhythm in all patients whenever possible and during left ventricular pacing, right ventricular pacing, and bi-ventricular pacing in CRT patients. LVPET and QWT were measured in 53 patients among whom 11 had a CRT device. A linear relationship between LVPET and QWT was observed (R Pearson coefficient = 0.926, P < 0.001) (Fig. 1). The intra-observatory and inter-observatory variabilities of QWT were 2.3% and 5.7% respectively. According to pacing setting in CRT patients, average variation of LVPET-Ped was equal to 23.3 ± 24.5%. Measurements of QWT from right carotid Doppler signal is an easy, reliable and reproducible method that can be used as a surrogate of LVPET. This could allow optimization of pacing sites location during CRT implant procedure.

Bronchial thermoplasty: activations predict response

BackgroundBronchial thermoplasty (BT) is an emerging bronchoscopic intervention for the treatment of severe asthma. The predictive factors for clinical response to BT are unknown. We examined the relationship between the number of radiofrequency activations applied and the treatment response observed.MethodsData were collected from 24 consecutive cases treated at three Australian centres from June 2014 to March 2016. The baseline characteristics were collated along with the activations delivered. The primary response measure was change in the Asthma Control Questionnaire-5 (ACQ-5) score measured at 6 months post BT. The relationship between change in outcome parameters and the number of activations delivered was explored.ResultsAll patients met the ERS/ATS definition for severe asthma. At 6 months post treatment, mean ACQ-5 improved from 3.3 ± 1.1 to 1.5 ± 1.1, p < 0.001. The minimal clinically significant improvement in ACQ-5 of ≥0.5 was observed in 21 out of 24 patients. The only significant variable that differed between the 21 responders and the three non-responders was the number of activations delivered, with 139 ± 11 activations in the non-responders, compared to 221 ± 45 activations in the responders (p < 0.01). A significant inverse correlation was found between change in ACQ-5 score and the number of activations, r = −0.43 (p < 0.05).ConclusionsThe number of activations delivered during BT has a role in determining clinical response to treatment.

MA15.09 Response to the Treatment Immediately before Nivolumab Monotherapy May Predict Clinical Response to Nivolumab

Nivolumab was approved in Japan on December 17, 2015 for previously treated non-small cell lung cancer (NSCLC). The expression of programmed death-ligand 1 (PD-L1) in tumor tissue is considered a predictive factor for clinical response to nivolumab. However, in Japan, there are no commercially available diagnostic kits for evaluating PD-L1 expression. In addition, little is known regarding other predictive factors of response to nivolumab monotherapy in patients with NSCLC. Therefore, we examined the relationships between the response to nivolumab monotherapy and clinical parameters in patients with NSCLC. Between December 2015 and April 2016, we performed a retrospective analysis of 50 patients with NSCLC treated with nivolumab monotherapy (3 mg/kg, every 2 weeks) at our Institution in the clinical setting. Baseline characteristics of patients who received nivolumab monotherapy were: median age, 65 years [range:39–76]; 60% male; 26% ECOG-PS 0, 64% ECOG-PS 1; 38% smoker; 58% stage IV disease, 22% postoperative recurrence; 80% non-squamous (SQ) NSCLC; 36% non-SQ NSCLC patients had active EGFR mutations; 20% second-line, 18% third-line. The objective response rate (ORR) for all patients treated with nivolumab monotherapy was 18% (95%CI 10–31). Univariate analysis revealed that predictive factors of response to nivolumab monotherapy were associated with “SQ”, “response to the treatment immediately before nivolumab monotherapy”, “therapeutic line of nivolumab (second-line and third-line treatment)” and “smoker” categories (Table 1). In the multivariate logistic regression analysis, the independent predictive factors were “SQ” (P = 0.0069) and “response to the treatment immediately before nivolumab monotherapy” (P < 0.0001) (Table 1). “Response to the treatment immediately before nivolumab monotherapy”, other than “SQ” histology may be predictors of clinical response to nivolumab in patients with NSCLC.

No predictive effect of body mass index on clinical response in patients with rheumatoid arthritis after 24weeks of biological disease-modifying antirheumatic drugs: a single-center study.

The aim of this study was to determine whether body mass index (BMI) is associated with clinical response to biologics in patients with rheumatoid arthritis (RA). We enrolled 68 patients with RA who were treated with biological disease-modifying antirheumatic drugs (bDMARDs). Biologics included abatacept, tocilizumab, and tumor necrosis factor-α (TNF-α) blockers (etanercept and adalimumab). Baseline BMI (kg/m(2)) was classified as normal (BMI < 23.0), overweight (23.0 ≤ BMI < 25.0), or obese (BMI ≥ 25.0). Improvement of disease activity score 28 (DAS28) and achievement of the European League Against Rheumatism (EULAR) remission and responses between baseline and 24weeks were our measures of clinical improvement. Mean baseline BMI before treatment with bDMARDs in patients with RA was 22.2 (SD 3.6). DAS28-ESR and DAS28-CRP were significantly reduced from baseline after 24weeks of treatment with bDMARDs (p < 0.001 of both). ∆DAS28-ESR and ∆DAS28-CRP were not found among patients with normal, overweight, or obese BMI (p = 0.133 and p = 0.255, respectively) nor were EULAR responses or EULAR remission (p = 0.540 and p = 0.957, respectively). Logistic regression analysis showed no relationship of BMI with EULAR clinical responses (p = 0.093 for good response and p = 0.878 for EULAR remission). This study reveals that BMI is not a predictive factor of clinical response to bDMARDs in patients with RA.

Predictors of clinical outcomes in patients with neuropsychiatric systemic lupus erythematosus

IntroductionNeuropsychiatric systemic lupus erythematosus (NPSLE), a serious organ disorder with a variety of symptoms, has diverse therapeutic outcomes because of the variability of NPSLE manifestations. A comprehensive association study of NPSLE among clinical and immunopathogenic aspects and outcomes has not been conducted. MethodsWe analyzed the laboratory data, NPSLE symptoms, and clinical outcomes at 1yr post-treatment and the profiles of 27 cytokines, chemokines and growth factors in cerebrospinal fluid (CSF) samples using the Bio-Plex Human 27-plex panel from 28 NPSLE patients. Univariate and multivariable competing risks regression analyses were used to determine the predictive factors of clinical response. We also tried to predict the outcome of NPSLE by the 27 cytokines/chemokines/growth factors using a weighted-voting (WV) algorithm. ResultsOf the two males and 26 females (92.9%), 16 were non-responders at 1yr post-treatment; in the final model, the independent predictors of non-responders were longer disease durations of SLE (odds ratio [OR]: 1.490, 95% confidence interval [CI]: 1.143–2.461, p=0.0003) and patients with more than one NPSLE symptom types (OR: 15.14, 95% CI: 1.227–452.1, p=0.0334). The pretreatment CSF interleukin (IL)-6, IL-10, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) levels were significantly higher in the non-responders (p=0.0207, p=0.0054, p=0.0242 and p=0.0077, respectively). We identified six “minimum predictive markers:” IL-10, TNF-α, IL-6, IFN-γ, IL-4 and IL-13 by a WV algorithm that showed the highest accuracy (70.83%) and highest Matthews correlation coefficient (54.23%). ConclusionsWe have devised a numerical prediction scoring system that was able to separate the non-responders from responders. The patients with longer disease durations of SLE and those with more than one NPSLE symptom types had poorer outcomes. Our findings may indicate both the importance of making a diagnosis at an earlier phase for better therapeutic response and the usefulness of measuring multiple cytokines to predict NPSLE therapeutic outcomes.

Predictive Factors for Clinical Response to Allergy Immunotherapy in Children With Asthma and Rhinitis

Q Li, M Li, W Yue, J Zhou, R Li, J Lin. Int Arch Allergy Immunol. 2014; 164(3): 210–217 This study sought to determine factors that could predict clinical response to allergen immunotherapy (AIT) in children. A total of 185 children aged 4 to 14 years with persistent mild asthma based on Global Initiative for Asthma (GINA) guidelines or a diagnosis of persistent allergic rhinitis based on Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines were included. The mean age was 8.0 years; 50% of patients were affected by rhinitis only. All patients were sensitized to house dust mite (HDM), and 89% were polysensitized. Charts of the 185 participants were retrospectively analyzed. Children were included …

Predictive factors of clinical response to cholinesterase inhibitors in mild and moderate Alzheimer's disease and mixed dementia: a one-year naturalistic study.

Naturalistic studies evaluate individuals in their usual way of living, presenting more "real-life" data regarding patients and their diseases. To investigate demographic, clinical, and genetic factors that could be predictive of good response to cholinesterase inhibitors (ChEI) treatment in Alzheimer's disease (AD) and AD + cerebrovascular disease (CVD). A total of 129 patients were diagnosed with AD or AD + CVD and with mild-to-moderate dementia. After a 12-month treatment, 97 patients completed the study. They were evaluated at baseline and after three, six, and 12 months of ChEI (donepezil or rivastigmine or galantamine) use. APOE genotype and CYP2D6 polymorphisms were determined for all of the participants. In each visit, we used cognitive, functional, mood, and behavior scales. We classified patients according to their scores in the Mini-Mental State Examination (MMSE). Good responders were defined as those scoring ≥2 in the MMSE at 12 months. The rate of good clinical response was 27.8%. In a longitudinal analysis, the patients with mild AD and also good responders at three months were considered to be good responders at 12 months. There was no correlation between ChEI dose, APOE and CYP2D6 polymorphisms, and the pattern of clinical response. A higher rate of good response was observed in this study compared to that in previous investigations. The pharmacogenetic aspects do not seem to have an influence in the response.

Predictive Factors for Clinical Response to Allergy Immunotherapy in Children with Asthma and Rhinitis

Background: To date, no predictive methods for the clinical response to allergy immunotherapy (AIT) are available. We sought to evaluate the pretreatment parameters used in diagnosing allergic asthma and/or rhinitis including allergen skin-prick test responses, serum specific and total IgE (sIgE and tIgE) levels and blood eosinophil counts, and to identify whether these can be used to predict clinical effectiveness in children treated with immunotherapy. Methods: This study involved 185 children who had undergone 3 years of standardized-quality house-dust mite subcutaneous immunotherapy. Clinical characteristics and laboratory parameters were analyzed. A multivariate unconditional logistic regression model and receiver operating characteristic curves were used. Predicted probabilities and predictive areas under the curve were calculated. Results: The clinical response to AIT was effective in 129/185 (69.7%) patients. Four variables were associated with clinical response by multivariate logistic analysis: tobacco smoke exposure [odds ratio (OR) 2.845 and 95% confidence interval (CI) 1.147-7.058; p = 0.024], a family history of atopy (OR 2.881 and 95% CI 1.240-6.692; p = 0.014), a serum tIgE level ≥965 kU/l (OR 5.917 and 95% CI 2.320-15.089; p = 0.000) and an sIgE/tIgE ratio ≥6% (OR 0.336 and 95% CI 0.124-0.911; p = 0.032). The sensitivity and specificity of the area under the curve of the serum tIgE were higher than those of serum sIgE and sIgE/tIgE ratio alone. Conclusion: Tobacco smoke exposure, atopic family history, serum tIgE and sIgE/tIgE ratio were in significant correlation with clinical response to AIT in children, which may be helpful for patient selection before immunotherapy. The serum tIgE is superior to both the serum sIgE/tIgE ratio and sIgE levels alone in predicting clinical effectiveness.

FGFR3 translocations in bladder cancer: differential sensitivity to HSP90 inhibition based on drug metabolism.

Activating mutations and/or overexpression of FGFR3 are common in bladder cancer, making FGFR3 an attractive therapeutic target in this disease. In addition, FGFR3 gene rearrangements have recently been described that define a unique subset of bladder tumors. Here, a selective HSP90 inhibitor, ganetespib, induced loss of FGFR3-TACC3 fusion protein expression and depletion of multiple oncogenic signaling proteins in RT112 bladder cells, resulting in potent cytotoxicity comparable with the pan-FGFR tyrosine kinase inhibitor BGJ398. However, in contrast to BGJ398, ganetespib exerted pleiotropic effects on additional mitogenic and survival pathways and could overcome the FGFR inhibitor-resistant phenotype of FGFR3 mutant-expressing 97-7 and MHG-U3 cells. Combinatorial benefit was observed when ganetespib was used with BGJ398 both in vitro and in vivo. Interestingly, two additional FGFR3 fusion-positive lines (RT4 and SW480) retained sensitivity to HSP90 inhibitor treatment by the ansamycins 17-AAG and 17-DMAG yet displayed intrinsic resistance to ganetespib or AUY922, both second-generation resorcinol-based compounds. Both cell lines, compared with RT112, expressed considerably higher levels of endogenous UGT1A enzyme; this phenotype resulted in a rapid glucuronidation-dependent metabolism and subsequent efflux of ganetespib from SW780 cells, thus providing a mechanism to account for the lack of bioactivity. Pharmacologic blockade of the molecular chaperone HSP90 represents a promising approach for treating bladder tumors driven by oncogenic gene rearrangements of FGFR3. Furthermore, UDP-glucuronosyltransferase enzyme expression may serve as a predictive factor for clinical response to resorcinol-based HSP90 inhibitors.

AB0337 Blood b cell counts as predictor of early clinical response after rituximab in patients with rheumatoid arthritis

BackgroundB cell depletion with rituximab is effective for reducing the symptoms and inhibiting the progression of joint damage in patients with rheumatoid arthritis (RA). However, the use of peripheral B...

FRI0001 Baseline soluble interleukin-6 receptor levels predict the clinical effectiveness of tocilizumab in patients with rheumatoid arthritis

BackgroundTocilizumab (TCZ), a humanized anti-IL-6 receptor (IL-6R) monoclonal antibody, specifically inhibits IL-6 activity by competitively binding to soluble (sIL-6R) and membrane-bound IL-6R. As for infliximab, a chimeric anti-TNF-α monoclonal antibody,...