Predictor Of Sustained Response Research Articles

Romiplostim-Free Response in Immune Thrombocytopenia: Experience in Cuenca-Ecuador

Background: Thrombopoietin analogues (TPO) achieve overall response rates of 75-80%, and in 60% are sustained with continuous administration for 6 months. In 10-30% of patients, response is maintained despite discontinuation of these drugs. Objectives: -Evaluate the percentage of patients with Romiplostim-free response criteria: platelet count ≥50,000/µL for at least six months (twenty-four consecutive weeks) in the absence of romiplostim and any other concomitant or rescue treatment for immune thrombocytopenia. -Determine sustained response factors after discontinuation of Romiplostim Materials and methods: Retrospective, analytical study in patients older than fifteen years with immune thrombocytopenia who accessed to romiplostim. Patients with systemic lupus erythematosus were included. Data was collected from the digitized medical records of a tertiary level hospital in Cuenca (Ecuador). The nonparametric Mann-Whitney U test using SPSS version 25 software (Chicago, IL) was used to establish comparisons between potential factors that may be associated with Romiplostin-free response. Results: a) Twenty-one patients with immune thrombocytopenia received romiplostim between August 2015 and February 2023 at some point.b) The median time from ITP diagnosis was 93 months (Q1 percentiles of 51.5 and Q3 106.5) for romiplostim use.c) The median duration of treatment with Romiplostim was 61 months (Q1 percentile range 18.5 and Q3 79).d) 37.5% (n:6) met Romiplostim-free response criteria, with a median follow-up of 7 months (Q1 percentile range of 3.5 and Q3 27.1). For this analysis, five patients were excluded (three who switched to eltrombopag, one who was lost to follow-up due to the health pandemic, one who had no response).e) One patient restarted Romiplostim after twenty months of sustained response.f) 23.8% (n:5) were able to discontinue romiplostim without restarting it. Conclusion(s): 1) 37.5% achieved Romiplostim-free response criteria 2) No predictors of sustained response were found for Romiplostim discontinuation (p>0.05). Bibliography: 1. Cooper N: Tapering and Discontinuation of Thrombopoietin Receptor Agonist Therapy in Patients with Immune Thrombocytopenia: Results from a Modified Delphi Panel. Acta Haematologica. 2021; 144:418-426 2. Iino M: Treatment-free remission after thrombopoietin receptor agonist discontinuation in patients with newly diagnosed immune thrombocytopenia: an observational retrospective analysis in real-world clinical practice. International Journal of Hematology. 2020;112(2):159-168 3. Neunert C: American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Advances. 2019; 3(23): 3829-3866 4. Provan D: Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Advances: 2019; 3(22): 3780-3817. 5. Zaja F: Tapering and discontinuation of thrombopoietin receptor agonists in immune thrombocytopenia: Real-world recommendations. Blood Reviews. 2020; 41: 100647

Predictors of sustained response in hepatitis B surface antigen-negative patients after peginterferon therapy: an observational study

Predictors of sustained response in hepatitis B surface antigen-negative patients after peginterferon therapy: an observational study

Predicting Sustained Clinical Response to Rituximab in Moderate to Severe Systemic Manifestations of Primary Sjögren Syndrome.

ObjectiveTo assess outcomes of repeat rituximab cycles and identify predictors of sustained clinical response in systemic manifestations of primary Sjögren syndrome (pSS).MethodsAn observational study was conducted in 40 rituximab‐treated patients with pSS. Clinical response was defined as a 3‐point or more reduction in the European League Against Rheumatism (EULAR) Sjögren Disease Activity Index (ESSDAI) at 6 months from baseline. Peripheral blood B cells were measured using highly sensitive flow cytometry. Predictors of sustained response (within two rituximab cycles) were analyzed using penalized logistic regression.ResultsThirty‐eight out of 40 patients had moderate to severe systemic disease (ESSDAI >5). Main domains were articular (73%), mucocutaneous (23%), hematological (20%), and nervous system (18%). Twenty‐eight out of 40 (70%) patients were on concomitant immunosuppressants. One hundred sixty‐nine rituximab cycles were administered with a total follow‐up of 165 patient‐years. In cycle 1 (C1), 29/40 (73%) achieved ESSDAI response. Of C1 responders, 23/29 received retreatment on clinical relapse, and 15/23 (65%) responded. Of the 8/23 patients who lost response, these were due to secondary non‐depletion and non‐response (2NDNR; 4/23 [17%] as we previously observed in systemic lupus erythematosus with antirituximab antibodies, inefficacy = 2/23, and other side effects = 2/23). Within two cycles, 13/40 (33%) discontinued therapy. In multivariable analysis, concomitant immunosuppressant (odds ratio 7.16 [95% confidence interval: 1.37–37.35]) and achieving complete B‐cell depletion (9.78 [1.32–72.25]) in C1 increased odds of response to rituximab. At 5 years, 57% of patients continued on rituximab.ConclusionOur data suggest that patients with pSS should be co‐prescribed immunosuppressant with rituximab, and treatment should aim to achieve complete depletion. About one in six patients develop 2NDNR in repeat cycles. Humanized or type 2 anti‐CD20 antibodies may improve clinical response in extra‐glandular pSS.

Predictors of sustained response and effects of the discontinuation of anti-calcitonin gene related peptide antibodies and reinitiation in resistant chronic migraine.

Guidelines for migraine prophylaxis suggest stopping medication after 6-12months to reevaluate treatment appropriateness. The Italian Medicines Agency set a mandatory regulation to stop anti-calcitonin gene related protein (CGRP) pathway monoclonal antibody (anti-CGRP mAb) treatments for 3months after 12 months of treatment. Herein, the effects of discontinuation and retreatment of anti-CGRP mAbs in resistant chronic migraine patients are assessed, evaluating predictive factors of sustained response. This was a monocentric prospective cohort study, enrolling 44 severe (resistant to ≥3 preventive treatments) chronic migraine patients (all with medication-overuse), treated with erenumab (54.5%) or galcanezumab (45.5%) for 12 months, who discontinued treatment for 3months and then restarted for 1month. Overall, patients reported an increasing deteriorating trend during the 3months of discontinuation. Monthly migraine days, number of analgesics, days with at least one analgesic used, a ≥50% response rate (reduction in monthly migraine days), and Migraine Disability Assessment Score and Headache Impact Test 6 total score, remained lower than baseline values, but increased compared to month 12 of treatment. All outcome measures decreased again during the month of retreatment. Patients who did not meet criteria for restarting treatment had a lower Migraine Disability Assessment Score (p=0.03) and Headache Impact Test 6 (p=0.01) score at baseline and better outcome measures during discontinuation compared to patients who restarted treatment. In most patients, the 3-month discontinuation of anti-CGRP mAbs resulted in progressive migraine deterioration that was rapidly reverted by retreatment. However, one-quarter of patients who reported better quality of life indices before treatment showed a sustained benefit during discontinuation and did not need retreatment.

Predictors of Sustained Response With Tofacitinib Therapy in Patients With Ulcerative Colitis.

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. We evaluate baseline characteristics as predictors of sustained response and remission in patients with ulcerative colitis receiving tofacitinib maintenance therapy. Patients with clinical response following OCTAVE Induction 1 and 2 entered OCTAVE Sustain and were rerandomized to receive tofacitinib 5 or 10mg twice daily or placebo. Baseline characteristics were stratified by week 52 efficacy endpoints (remission, sustained remission, clinical response, sustained clinical response). Associations between baseline characteristics and efficacy endpoints were evaluated using logistic regression analyses. Overall, 170 of 487 (34.9%) patients were in remission at week 52. In multivariable modeling, endoscopic subscore at baseline of OCTAVE Induction 1 and 2 (2 vs 3; odds ratio [OR], 1.60; 95% confidence interval [CI], 1.06-2.44]), partial Mayo score (<2 vs ≥2; OR, 1.92; 95% CI, 1.27-2.90), and age (per 10-years; OR, 1.19; 95% CI, 1.02-1.39) at baseline of OCTAVE Sustain (following 8 weeks' tofacitinib induction therapy) were associated with higher odds of remission at week 52. Oral corticosteroid use (OR, 0.63; 95% CI, 0.42-0.96) and C-reactive protein (per unit; OR, 0.94; 95% CI, 0.89-0.99) at baseline of OCTAVE Sustain were associated with reduced likelihood of remission at week 52. In general, opposite associations were observed for time to loss of response. Patients with greater clinical improvement after 8 weeks of tofacitinib induction therapy are more likely to maintain response or remission with tofacitinib regardless of dose received during maintenance, highlighting the importance of a robust response to induction therapy.

P254 Factors that may predict the need for infliximab optimization in Crohn’s disease

Abstract Background Biological therapy has revolutionized treatment of Crohn’s Disease (CD), increasing the rate of disease remission. Despite this, a significant percentage of patients present partial response or loss of response over time. These patients need optimization of therapy, whether by increasing the dosage or reducing the interval between infusions. The main objective of this study was to identify possible factors related to the need to optimize the dose of infliximab (IFX) in patients with CD. This finding can facilitate the early identification of the need for therapeutic optimization, reducing the risks of unfavorable evolution and decreasing costs related to the disease. Methods Retrospective and prospective maintained database of CD patients under IFX treatment being followed up in the Infusion Center at the Day Hospital of the Hospital de Clínicas de Porto Alegre, Brazil, from 2009 to 2018. Epidemiological, clinical, laboratory and endoscopic characteristics that correlate with worse prognosis of CD were evaluated. The main goal of the study was to identify possible factors related to the need for (IFX) optimization. Results 121 patients were evaluated. Of these, 58 (47,93%) needed the optimization of the IFX dosage. The only variables that had significant statistical difference between the groups with or without need for optimization were anemia (p=0.019) and C reactive protein (CRP) which were persistently elevated in week 14 (p=0.039). After the adjustment with the multivariate model, only the elevated CRP during week 14 was still statistically significant, with a 119% greater risk of optimizing treatment when compared to those of normal CRP. Conclusion Among the factors studied, only the maintenance of higher CRP during week 14 was associated to the need for optimization of the IFX dose. This finding agrees with the literature that describes week 14 as an ideal moment for evaluating the serum levels of immunobiologics as a predictor of sustained response. Thus, in the absence of therapeutic drug monitoring, we could look at persistently high CRP as a marker of the need for therapeutic optimization. This finding needs to be confirmed in prospective studies.

Sustained response to onabotulinumtoxin A in patients with chronic migraine: real-life data

BackgroundTreatment with onabotulinumtoxin A (BT-A) is safe and effective for chronic migraine (CM). Several studies assessed possible predictors of response to treatment with BT-A, but there is little knowledge on the frequency and predictors of sustained response. The aim of this study was to evaluate sustained response to BT-A in patients with CM.Main bodyIn this prospective open-label study, 115 patients with CM and treated with BT-A were consecutively enrolled in two Italian headache centers and followed up for 15 months. Anytime responders were defined as those patients who achieved a ≥ 50% reduction in headache days during any three-month treatment cycle compared with the 3 months prior to initiation of BT-A treatment. Sustained responders were defined as those who achieved a ≥ 50% reduction in headache days within the third treatment cycle and maintained response until the end of follow-up. Non-responders were defined as those patients who never achieved a ≥ 50% reduction in headache days during the follow-up. Headache characteristics prior to BT-A treatment were assessed in order to evaluate their ability in predicting treatment response.The 115 enrolled patients (84.3% female; median age 50 years) had a median migraine duration of 30 years (interquartile range 22–38). At the end of follow-up, 66 patients (57.4%) were classified as anytime responders. Among the 51 patients who achieved a clinical response within the third month of treatment, 33 (64.7%) were sustained responders. Patients with sustained response had a lower CM duration (median 31 vs 65 months; P = 0.030) and a lower number of headache days (median 25 vs 30; P = 0.013) at baseline compared with non-responders.ConclusionsAbout two thirds of patients who gain ≥50% response to BT-A within the third cycle of treatment maintain this positive response over time. More recent onset of CM and more headache-free days at baseline are associated with sustained response. We suggest not to delay preventive treatment of CM with BT-A, in order to increase the likelihood to achieve sustained clinical response.

Quantitation of large, middle and small hepatitis B surface proteins in HBeAg-positive patients treated with peginterferon alfa-2a.

Hepatitis B virus (HBV) contains three viral surface proteins, large, middle and small hepatitis B surface protein (LHBs, MHBs, SHBs). Proportions of LHBs and MHBs are lower in patients with inactive vs active chronic infection. Interferon alfa may convert hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) to an inactive carrier state, but prediction of sustained response is unsatisfactory. The aim of this study was to test the hypothesis that quantification of MHBs and LHBs may allow for a better prognosis of therapeutic response than total hepatitis B surface antigen (HBsAg) concentration. Hepatitis B surface proteins were measured before and during peginterferon alfa-2a therapy in serum from 127 Asian patients with HBeAg-positive CHB. Sustained response was defined as HBeAg seroconversion 24weeks post-treatment. Mean total HBs levels were significantly lower in responders vs nonresponders at all time points (P<.05) and decreased steadily during the initial 24weeks treatment (by 1.16 vs 0.86ng/mL in responders/nonresponders respectively) with unchanged relative proportions. Genotype B had a two-fold higher proportion of LHBs than genotype C (13% vs 6%). HBV DNA, HBeAg, HBsAg and HBs protein levels predicted response equally well but not optimally (area under the receiver operating characteristic curve values >0.70). Hepatitis B surface protein levels differ by HBV genotype. However, quantification of HBs proteins has no advantage over the already established HBsAg assays to predict response to peginterferon alfa-2a therapy in HBeAg-positive patients.

Predictive factors associated with three years of response to HbA1c goals with exenatide QW or insulin glargine: Post-hoc analysis of the DURATION-3 study.

This post-hoc analysis of the DURATION-3 study aimed to identify factors associated with sustained glycaemic response with exenatide once weekly (QW) or insulin glargine (IG) among patients with type 2 diabetes. Response was defined as achieving treatment target of HbA1c <7.0% (<53 mmol/mol) at Week 26; sustained responders maintained the treatment target for ≥80% of remaining visits, including one during the final 6 months. Of 467 patients, 287 (61.5%) completed 156 weeks of treatment. At Week 26, 175 patients (61.0%) (exenatide QW, n = 95; IG, n = 80) achieved an HbA1c response. At Week 156, 84 of 175 responders (48.0%) had sustained response, with more sustained responders with exenatide QW (22.7% vs 13.9% with IG; P < 0.03). Logistic regression identified three predictors of sustained response: (a) exenatide QW vs IG treatment (odds ratio, 2.584 [95% confidence interval, 1.288-5.187]; P = 0.0075), (b) lower HbA1c at Week 26 (0.139 [0.053-0.366]; P < 0.0001), and (c) lower fasting serum glucose at Week 26 (0.693 [0.541-0.888]; P = 0.0037). A regression model was used to estimate the likelihood of sustained response with either treatment. This analysis provides a helpful tool for predicting sustained response with exenatide QW or IG.

Long-term outcome of 251 patients with Takayasu arteritis on combination immunosuppressant therapy: Single centre experience from a large tertiary care teaching hospital in Southern India.

Long-term outcome studies in Takayasu arteritis (TA) are few and limited by small sample size. In this study, we analysed the outcome of treatment in a large series of TA patients with a minimum follow-up period of ≥12 months by objective instruments. Patients with TA satisfying the 1990 ACR, Ishikawa's, Sharma's or EULAR/PRESS criteria were recruited from our clinics between 1998 and 2016. Only patients with a minimum follow up of 12 months were studied. Data related to clinical presentation, disease extent (DEI.Tak score), activity [Indian Takayasu arteritis clinical activity score, that is, ITAS-A (CRP)] and damage score [Takayasu arteritis damage score (TADS)], angiography and treatment were collected for all patients. Response to treatment was categorised as complete response (CR), partial response (PR) or refractory disease. Patients with sustained CR on prednisolone dose of ≤5mg/day were classified as having sustained inactive disease. Appropriate statistical tests were used for parametric and non-parametric data. Relapse free survival was projected by Kaplan-Meir curve. Cox proportional hazards regression plot was used to compare the efficacy of medications. Predictors of sustained response were identified by logistic regression and a prediction model was constructed. Among 503 TA patients examined during study period, 251 had follow-up of ≥12 months and were included in this study. Median follow-up duration was 42 months (IQR: 24-81, maximum 240 months). Patients (81.7% females, mean age of 29.2 ± 11.8 years, symptom duration of 24 [6-70] months) were treated by a uniform protocol that included high dose steroids (n = 239) plus concurrent steroid-sparing immunosuppressant (n = 235) with mycophenolate in majority. Biological agents (n = 44 patients) and revascularisation procedures were used in symptomatic patients after control of disease activity. At 1st follow-up, CR (ITAS2010 = 0, CRP < 6mg/L and non-progressive disease on angiography) was observed in 173 (68.9%), partial response (PR) in 42 (16.7%) and no response was seen in only 36 (14%) patients. CR was sustained till the last follow up in 116 (65.9%) of 173 patients with initial CR, while 87 (49.4%) of them achieved sustained inactive disease. Disease activity relapsed at a median duration of 37 (29.9-44.1) months in 56 patients. Cumulative relapse free survival was 93%, 73%, 66% and 52% at 1, 3, 5 and 10 years, respectively. Baseline CRP < 6.2, DEI.Tak < 9 and angiographic type 4 disease predicted sustained inactive disease and a model comprising these parameters showed sensitivity and specificity of 70% and 61.1%. Two fatalities were observed. New vascular lesions during follow up were observed in 50 (19.9%) patients. Overall, 92.8% had at least one period of CR or PR while 7.2% were refractory to treatment till the last follow up. Damage progression (∆TADS > 1) was arrested in 68% of patients and was lower in patients with sustained inactive disease [0 (0-1)] as compared to the rest [1 (0-2.75)], p = 0.000. Both early response as well as cumulative hazard for relapse were similar between patients initiated on 0.5 and 1mg/kg/day steroids. Our strategy of upfront combination immunosuppressant therapy stabilised disease activity in 92.8% of patients, while 7.2% had true refractory disease. Relapse free survival was 66% at 5 years and 52% at 10 years. Damage progression was arrested in 68% and only 2 fatalities were observed. Initial steroid dose of 0.5mg/kg/day had similar efficacy as 1mg/kg/day dose.

Tu1619 - Sustained Response and Predictors of Sustained Response in Patients who Respond to Multiple Courses of Rifaximin for Diarrhea-Predominant Irritable Bowel Syndrome

Tu1619 - Sustained Response and Predictors of Sustained Response in Patients who Respond to Multiple Courses of Rifaximin for Diarrhea-Predominant Irritable Bowel Syndrome

Predictors of Response in Patients With Postherpetic Neuralgia and HIV-Associated Neuropathy Treated With the 8% Capsaicin Patch (Qutenza).

Qutenza is a high-dose capsaicin patch used to relieve neuropathic pain from postherpetic neuralgia (PHN) and HIV-associated neuropathy (HIV-AN). In clinical studies, some patients had a dramatic response to the capsaicin patch. Our objective was to determine the baseline characteristics of patients who best benefit from capsaicin patch treatment. We conducted a meta-analysis of 6 completed randomized and controlled Qutenza studies by pooling individual patient data. Sustained response was defined as>50% decrease in the mean pain intensity from baseline to weeks 2 to 12, and Complete Response as an average pain intensity score≤1 during weeks 2 to 12. Logistic regression was used to identify predictors of response and Complete Response, and subgroups of patients who respond best to the capsaicin patch. Baseline pain intensity score (BPIS)≤4 was a predictor of Sustained and Complete Response in PHN and HIV-AN patients; absence of allodynia and presence of hypoesthesia, and a McGill Pain Questionnaire (MPQ) sensory score <22 were predictors of Sustained Response in PHN patients; female sex was a predictor of Sustained and Complete Response in HIV-AN patients. Thus, characteristics associated with the highest chance of responding to the capsaicin patch were, for PHN, BPIS≤4, MPQ sensory score≤22, absence of allodynia, and presence of hypoesthesia; for HIV-AN, they were female sex and BPIS≤4. Patients with these characteristics had a statistically significantly greater chance of responding to the capsaicin patch than other patients. We identified subpopulations of PHN and HIV-AN patients likely to benefit from the capsaicin patch.

Durability of Nucleos(t)ide Analogues Treatment in Patients With Chronic Hepatitis B.

Long-term nucleos(t)ide analogues (NUCs) treatment is usually required for patients with chronic hepatitis B (CHB). However, whether discontinuation of NUCs is possible in selected patients remains debated. The aim of this study was to assess the durability of NUCs and predictors of sustained response after cessation of NUCs.Ninety-three CHB patients (29 HBeAg-positive and 64 HBeAg-negative) from 2 medical centers in Taiwan with discontinuation of NUCs after a median of 3 years’ treatment were retrospectively reviewed. Fifteen (51.7%) HBeAg-positive and 57 (89.1%) HBeAg-negative patients achieved APASL treatment endpoints. Virological relapse (VR) and clinical relapse (CR) were defined according to APASL guidelines.Achieving APASL endpoint was associated with longer median time to CR in HBeAg-positive patients, but not in HBeAg-negative cases. The cumulative 1-year VR and CR rates were 55.3% and 14.4% in HBeAg-positive patients, and 77.7% and 41.9% in HBeAg-negative patients, respectively. In HBeAg-negative patients, baseline HBV DNA >105 IU/mL was the only predictor of VR (hazard ratio [HR] = 2.277, P = 0.019) and CR (HR = 3.378, P = 0.014). HBsAg >200 IU/mL at the end of treatment (EOT) was associated with CR (HR = 3.573, P = 0.023) in patients developing VR. HBeAg-negative patients with low baseline viral loads and low HBsAg levels at EOT had minimal risk of CR after achieving APASL treatment endpoint (P = 0.016).The VR rate is high, but the risk of CR is low within 1 year with consolidation treatment after HBeAg seroconversion. Longer consolidation treatment to reduce the risk of VR should be considered in HBeAg-positive patients. As high risk of VR and CR, cessation of NUCs therapy could be considered only in selected HBeAg-negative patients.

Baseline and On-treatment Predictors of Chronic Hepatitis B Patients Receiving Pegylated Interferon Therapy in Asia

Of currently available drugs for the treatment of chronic hepatitis B, pegylated interferon (peg-IFN) offers the highest rate of off-treatment sustained response with the finite course of treatment in the absence of viral resistance. However, its clinical use is compromised by the frequent occurrence of side-effects and the uncertainty as to whether a patient will actually benefit from this treatment. It is therefore a major challenge to identify accurate predictors of sustained response to peg-IFN. These are essential for selecting the optimal candidates for peg-IFN therapy, as well as for making decisions of termination of treatment for nonresponders. This article reviews the recent knowledge focusing on the following topics: baseline and on-treatment viral and host factors in the response to peg-IFN therapy, as well as response-guided therapy for chronic hepatitis B, particularly in the Asian population.

Commentary: HBsAg levels as predictor of sustained response to peg interferon in HBeAg‐negative chronic hepatitis B

Commentary: <scp>HB</scp>s<scp>A</scp>g levels as predictor of sustained response to peg interferon in <scp>HB</scp>e<scp>A</scp>g‐negative chronic hepatitis <scp>B</scp>

Rapid virological response as a predictor of sustained response in HCV-infected patients with persistently normal alanine aminotransferase levels: A multicenter study

Rapid virological response (RVR) is now considered the strongest predictor of sustained virological response (SVR) in patients with HCV undergoing antiviral treatment, and thus, shorter antiviral treatment for these patients has been suggested. However, no data exist on the predictive value of RVR in HCV carriers with normal ALT values. A total of 137 patients with persistently normal ALT treated with peginterferon alfa 2a and ribavirin were studied. Fifteen patients dropped out early because of side effects, and in 10 patients with HCV-1 treatment was discontinued because of lack of early virological response (EVR). RVR was observed in 68% of the patients (42% patients with HCV-1, 90% HCV-2 and 64% HCV-3). An end-of-treatment response was observed in 86% of the patients (68% HCV-1, 100% HCV-2 and 91% HCV-3). SVR was maintained in 91 patients (46% HCV-1, 97% HCV-2 and 82% HCV-3). Overall, 92% patients with rapid response did obtain HCV eradication vs only 38% of those without rapid response. HCV-1 patients with baseline HCV RNA <400×10(3) IU/mL were more likely to achieve RVR and SVR than those with higher HCV RNA levels. We conclude that patients with genotype 1 and normal ALT who achieve HCV RNA negativity at week 4 may have a higher probability of eradicating their infection. Because of the concomitant favourable demographic and virological features often found in this particular subset of patients, the duration of therapy in these people might be shortened in the case of RVR. Persistently normal alanine aminotransferase levels patients with genotype 2 or 3 have a high chance of achieving SVR, so retesting of HCV RNA during treatment may have no additional practical value in these subjects.

Predictors of Sustained Response to Infliximab in Patients With Crohn's Disease: A Single Cohort Study

Background and Aims: The three anti-TNF agents infliximab (IFX), adalimumab (ADA) and certolizumab pegol (CZP) have demonstrated similar efficacy in induction and maintenance of response and remission in Crohn's disease (CD) treatment. Given the comparability of these drugs, patient's preferences may influence the choice of the product. However, data on patient's preferences for choosing anti-TNF agents are lacking. We therefore aimed to assess the CD patient's appraisal to select the drug of his choice and to identify factors guiding this decision. Methods: A prospective survey among anti-TNF-naive CD patients was performed. Patients were provided a description of the three anti-TNF agents focusing on indication, application mode (s.c. vs. i.v.), application time intervals, setting of application (hospital vs. private practice vs. patient's home), average time to apply the medication per month, typical side effects, and the scientific evidence of efficacy and safety available for every drug. Patients answered a questionnaire consisting of 17 questions, covering demographic, disease-specific, and medication data. Results: Hundred patients (47f/53m, mean age 45±16 years) completed the questionnaire. Disease duration was 5 years in 62% of patients. Disease location was ileal in 33%, colonic in 40%, and ileocolonic in 27%. Disease phenotype was inflammatory in 68%, stenosing in 29%, and internally fistulizing in 3% of patients. Additionally, 20% had perianal fistulizing disease. Patients were already treated with the following drugs: mesalamines 61%, budesonide 44%, prednisone 97%, thiopurines 78%, methotrexate 16%. In total, 30% had already heard about IFX, 20% about ADA, and 11% about CZP. Thirty-six percent voted for treatment with ADA, 28% for CZP, and 25% for IFX, whereas 11% were undecided. The following factors influenced the patient's decision for choosing a specific anti-TNF drug (several answers possible): side effects 76%, physician's recommendation 66%, application mode 54%, efficacy experience 52%, time to spend for therapy 27%, patient's recommendations 21%, interactions with other medications 12%. The single most important factor for choosing a specific anti-TNF was (1 answer): side effect profile 35%, physician's recommendation 22%, efficacy experience 21%, application mode 13%, patient's recommendations 5%, time spent for therapy 3%, interaction with other medications 1%. Conclusions: The majority of patients preferred anti-TNF syringes to infusions. The safety profile of the drugs and the physician's recommendation are major factors influencing the patient's choice for a specific anti-TNF drug. Patient's issues about safety and lifestyle habits should be taken into account when prescribing specific anti-TNF formulations.

New developments in antiviral therapy for chronic hepatitis B

Chronic hepatitis B affects approximately 400 million people in the world with a substantial disease burden like liver cirrhosis and hepatocellular carcinoma (HCC). Treatment for chronic hepatitis B has improved dramatically in the last decade, resulting in more patients achieving a state of inactive disease. Currently two treatment strategies are available; treatment with peginterferon (peg-IFN) or nucleos(t)ide analogues with the aim to suppress hepatitis B virus (HBV) DNA to subsequently avoid the development of cirrhosis and HCC. Unfortunately, treatment with peg-IFN can be suboptimal with important adverse effects and nucleos(t)ide analogues provoke resistance. At present, no new promising compounds attacking the HBV life cycle are in development. However, for prediction of sustained response or treatment failure, data from the long-term large peg-IFN trials provide important response markers. For the future the focus is to achieve HBsAg loss and anti-HBs conversion which is the closest the treatment can get to a cure. This review summarizes the current treatment options with their response rates and discusses future strategies for chronic hepatitis B treatment.

A 2‐log drop in viral load at 1 month is the best predictor of sustained response in HCV patients with normal ALT: a kinetic prospective study

The most reliable predictor of a sustained virological response in patients with persistently normal ALT has not been identified. We analysed 17 patients with genotype 1 chronic HCV who underwent therapy with pegylated interferon alfa 2b and ribavirin for 48 weeks. Two patients discontinued therapy within 28 days because of side effects and the remaining 15 patients were analysed in detail. An analysis of on treatment virological response using area under the receiver operating characteristic analyses showed that a 2 log drop in HCV RNA at day 28 was the best predictor of a sustained virological response and a failure to reduce viral load by 2 logs correctly identified patients with a low (<15%) probability of achieving a sustained virological response. Introduction of this early discontinuation rule in patients with normal ALT would allow nearly half of the patients to discontinue futile therapy at an early stage.

Efficacy of Pre-S-containing HBV Vaccine Combined with Lamivudine in the Treatment of Chronic HBV Infection

Treatment of chronic hepatitis B (CHB) is difficult. The response rate to interferon (IFN) as well as nucleoside analogs is not more than 30% in general. While interferon has many side effects, development of resistance in most of the nucleoside analogs precludes long-term use. Both groups of drugs are most efficacious in patients who already had or develop strong cellular immunity with treatment. A pre-S2-containing vaccine was shown to enhance cellular immunity and suppress hepatitis B virus (HBV)-DNA in subjects with chronic hepatitis B. We aimed to test the efficacy of short-term use of a nucleoside analog in combination with a pre-S2-containing vaccine in patients with CHB. In this open study, 48 consecutive patients (32 males and 16 females, mean age +/- SD: 33 +/- 12 years) with CHB without cirrhosis were treated with 100 mg/day lamivudine and four weekly intramuscular injections of Genhevac B 20 mcg (six doses) for 24 weeks. While 19 patients were hepatitis B e antigen (HBeAg) positive (+ve), 29 patients were Anti-HBe/HBV-DNA +ve at the outset. Response was defined as seroconversion to anti-HBe in HBeAg +ve subjects and normalization of alanine aminotransferase (ALT) with loss of HBV-DNA in anti-HBe/HBV-DNA +ve subjects. HBeAg seroconversion occurred in 5/19 subjects (26%). Eighteen of 29 anti-HBe/HBV-DNA +ves responded. In the follow-up, while relapse was not observed in any of the patients who seroconverted, 11/18 from the anti-HBe/HBV-DNA +ve group relapsed, resulting in a sustained response (SR) rate of 24% in this group. All the relapses happened in the first 48 weeks of follow-up, with no relapse thereafter. Pretreatment high serum HBV-DNA was a strong negative predictor of sustained response (SR) in HBeAg +ve group. Pretreatment serum ALT over 2 x upper limit of normal and HBV-DNA less than 200 pg/ml appeared positive predictors. None of HBeAg +ve previous interferon failures responded. Twenty-four weeks of lamivudine and hepatitis B vaccine treatment induces SR in around 1/4 of the patients with CHB. Most of the responders had high ALT and relatively low DNA.