Second-line Drug In Patients Research Articles

Clinical study reveals the efficacy of sirolimus in treating primary immune thrombocytopenia: findings from a single-center study.

Immune thrombocytopenia (ITP) is an autoimmune disease that arises because of self-destruction of circulating platelets. The mechanism remains complicated and lacks a standard clinical treatment. Current first-line and second-line medications for ITP have shown limited effectiveness, necessitating the exploration of new therapeutic options. Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor that has been demonstrated to inhibit lymphocyte activity, indicating potential for SRL in the treatment of ITP. This study aimed to evaluate the clinical efficacy of sirolimus as a second-line drug in patients with ITP. The starting dose of sirolimus for adults ranged from 2 to 4 mg/day, with a maintenance dose of 1 to 2 mg/day. For children, the starting dose was 1-2 mg/day, with a maintenance dose of 0.5-1 mg/day. The dosage could be adjusted if needed to maintain a specific blood concentration of sirolimus, typically between 5 and 15 ng/ml, throughout the treatment period. After 3 months, the overall response rate was 60% (12/20), with 30% of patients (6/20) achieving a complete response (CR) and 30% (6/20) achieving a partial response (PR). The CR rate at 6 months remained consistent with the 3-month assessment. No major adverse events were reported, indicating that sirolimus was well tolerated and safe. Analysis of peripheral blood Treg cell percentages in both the control and ITP showed no significant difference before treatment. The percentage of Treg cells increased after treatment with sirolimus, suggesting that sirolimus increases Treg cells. These findings suggest that sirolimus serves as an effective second-line treatment option for ITP, demonstrating favorable clinical efficacy.

Second- and third-line treatment agents in autoimmune hepatitis (AIH): Where do we stand?

Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology that can lead to end stage liver disease if left without treatment. Corticosteroids with or without azathioprine (AZA) are considered the recommended standard first-line treatment option for the induction and maintenance of remission. The aim of treatment is to achieve complete biochemical response (CBR), defined by normal transaminases and immunoglobulin G (IgG) within 6–12 months after treatment initiation. However, response rates to standard treatment vary widely as approximately 10–25% of cases develop intolerance, insufficient response, or rarely non-response to AZA. Mycophenolate mofetil (MMF) is an effective and safe alternative first-line treatment in AIH, based on its high rates of CBR among treatment-naive patients, but can also be considered as second-line drug in patients with poor response or intolerance to AZA. However, even after the administration of second line treatment there is a small proportion of patients with refractory disease that bear the highest probability of developing decompensated cirrhosis and hepatocellular carcinoma. For this difficult to treat subgroup of patients third-line treatments are warranted. Therefore, the aim of this review is to summarize the current evidence on second- and third-line therapies for AIH, as well as, to set the background for future perspectives on safer and more efficient treatment strategies.

Clinico-biochemical Profile of Biopsy-proven Minimal Change Disease in Adults from a Tertiary Care Center in South India.

Minimal change disease (MCD) is the most common cause of nephrotic syndrome (NS) in children, and in adults, it contributes to 10%-25% of NS. MCD in adults follows a slightly different course associated with increased incidence of steroid resistance, hematuria, and HTN. This is a prospective-record analysis study aimed to analyze the profile of MCD in adults, response to treatment, and relapse rates. A retrospective observational study was carried out and data were collected retrospectively from all biopsy-proven MCD patients between 2012 and 2018. A total of 86 adults were diagnosed to have biopsy-proven MCD. Of these, 32 were excluded due to insufficient data/lost for follow-up. The IBM SPSS Statistics version 22.0 was used for the statistical analysis. Descriptive analysis includes expression of all the explanatory and outcome variables in terms of frequency and proportions for categorical variables whereas in terms of mean ± standard deviation for continuous variables. Chi-square test was used to compare the age, gender, remission, renal failure and response of different drugs, treatment durations, comorbidity conditions, relapse episodes, and different types of infections based on the degree of proteinuria among study patients. A total of 54 biopsy-proven adult MCD patients were analyzed. The mean age of the patients studied was 36.67 years, with the oldest patient being 76 years. In the study group, 37 (68.5%) patients were male and 14 (31.5%) were female. In the study population, 20 (37%) were hypertensive, 3 (5.6%) were diabetic, and 10 (18.5%) had renal failure at presentation. On treatment, 52 out of 54 patients received steroids, of which 41 (75.9%) were steroid responsive, 6 (11.1%) steroid dependent, and 7 (13%) steroid resistant. The mean time for remission in steroidsensitive patients was 8.8 weeks. Among the steroid-dependent and steroid-resistant patients, 11 patients received calcineurin inhibitors (CNIs), of which 3 were CNI resistant. In the study Group 1 patient received cyclophosphamide and two received rituximab. In the study population, two patients failed to achieve remission and one patient was initiated on hemodialysis and later lost for follow-up. Minimal change NS is a type of NS which is highly responsive to steroids with good prognosis in children. Adult MCD patients require a higher and prolonged course of steroid when compared to children. CNIs and rituximab form a promising second-line drug in patients who are steroid resistant/dependent. However, CNI dependency or relapse after stopping steroids is a concern.

New Second-Line Treatment for B-Cell Lymphoma.

Axicabtagene ciloleucel (Yescarta) has been approved for use as a second-line drug in patients with large B-cell lymphoma who are resistant to, or who relapse within 12 months of, first-line chemoimmunotherapy.Confirming the patient's identity and matching it to the drug are critical as this is an autologous infusion. Nurses should premedicate patients to minimize the risk of hypersensitivity reactions.

Real-world treatment intensities and pathways of macular edema following retinal vein occlusion in Korea from Common Data Model in ophthalmology

Despite many studies, optimal treatment sequences or intervals are still questionable in retinal vein occlusion (RVO) macular edema. The aim of this study was to examine the real-world treatment patterns of RVO macular edema. A retrospective analysis of the Observational Medical Outcomes Partnership Common Data Model, a distributed research network, of four large tertiary referral centers (n = 9,202,032) identified 3286 eligible. We visualized treatment pathways (prescription volume and treatment sequence) with sunburst and Sankey diagrams. We calculated the average number of intravitreal injections per patient in the first and second years to evaluate the treatment intensities. Bevacizumab was the most popular first-line drug (80.9%), followed by triamcinolone (15.1%) and dexamethasone (2.28%). Triamcinolone was the most popular drug (8.88%), followed by dexamethasone (6.08%) in patients who began treatment with anti-vascular endothelial growth factor (VEGF) agents. The average number of all intravitreal injections per person decreased in the second year compared with the first year. The average number of injections per person in the first year increased throughout the study. Bevacizumab was the most popular first-line drug and steroids were considered the most common as second-line drugs in patients first treated with anti-VEGF agents. Intensive treatment patterns may cause an increase in intravitreal injections.

SGLT-2 Inhibitors and DPP-4 Inhibitors as Second-Line Drugs in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Clinical Trials.

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors are both novel and second-line therapies in type 2 diabetes mellitus, yet no well-rounded comparison of these two drugs has been published. Upon searching randomized controlled trials in databases from inception to July 2018, we collected studies on the efficacy or safety of SGLT-2 inhibitors compared with those of DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. A total of 12 randomized controlled studies including 4342 patients were included in this meta-analysis. Compared with DPP-4 inhibitors, SGLT-2 inhibitors achieved greater reductions in HbA1c (SMD -0.22; 95% CI: -0.30, -0.14; p=0.000) and fasting plasma glucose (SMD -0.48; 95% CI: -0.56, -0.41; p=0.000). In addition, these reductions increased with a prolonged treatment duration from 12 to 78 weeks. Geographically, significant reductions of SGLT-2 inhibitors in HbA1c and FPG were found in North America and Europe, but not in Asia. Furthermore, SGLT-2 inhibitors showed greater reductions in body weight (SMD -0.72; 95% CI: -0.81, -0.63; p=0.000) from baseline, with an increased incidence of genital infections (OR 4.49; 95% CI: 2.96, 6.83; p=0.000) and pollakiuria (OR 2.24; 95% CI: 1.05, 4.79; p=0.037) and a decreased incidence of hypertension and hyperglycemia. Overall, the current meta-analysis demonstrated that compared to DPP-4 inhibitors, SGLT-2 inhibitors have beneficial effects on HbA1c, FPG, body weight, SBP, DBP, and HDL-cholesterol in patients with type 2 diabetes. However, SGLT-2 inhibitors are associated with increased total cholesterol and LDL-cholesterol and a higher incidence of genital infections and pollakiuria.

Population pharmacokinetics of moxifloxacin, cycloserine, p-aminosalicylic acid and kanamycin for the treatment of multi-drug-resistant tuberculosis.

Control of multi-drug-resistant tuberculosis (MDR-TB) requires extensive, supervised chemotherapy because second-line anti-TB drugs have a narrower therapeutic range than first-line drugs. This study aimed to develop population pharmacokinetic (PK) models for second-line drugs in patients with MDR-TB, evaluate the recommended dosage regimens and, if necessary, suggest new dosage regimens. A prospective, single-centre PK study was performed on second-line anti-TB drugs in patients with MDR-TB. Moxifloxacin, cycloserine, p-aminosalicylic acid (PAS), kanamycin and other second-line drugs were administered to the patients. Plasma concentrations were analysed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Population PK models were developed using non-linear mixed effect modelling (NONMEM, Version 7.30; ICON Development Solutions, Ellicott City, MD, USA). Simulations were performed using the calculated PK parameters. The respective absorption rate constant, apparent clearance and apparent volume of distribution values were as follows: 0.305/h, 9.37 L/h and 56.7 L for moxifloxacin; 0.135/h, 1.38 L/h and 10.5 L for cycloserine; 0.510/h, 30.8 L/h and 79.4 L for PAS; and 1.67/h, 3.75 L/h and 15.2 L for kanamycin. The simulations showed that the following dosage regimens were more likely to be within the recommended concentration ranges than the raw data in this study: 200 mg of moxifloxacin once daily (QD) (patient weight <50 kg) and 400 mg of moxifloxacin QD (patient weight ≥50 kg), 500-750 mg of cycloserine QD, 4.95-6.6 g of PAS twice daily and 750-1000 mg of intramuscular kanamycin QD. These findings indicate that the recommended doses should be revised to improve the clinical outcomes of MDR-TB treatment.

Implications of Failure to Routinely Diagnose Resistance to Second-Line Drugs in Patients With Rifampicin-Resistant Tuberculosis on Xpert MTB/RIF: A Multisite Observational Study.

Xpert MTB/RIF (Xpert) detects rifampicin-resistant tuberculosis (RR-tuberculosis), enabling physicians to rapidly initiate a World Health Organization-recommended 5-drug regimen while awaiting second-line drug-susceptibility test (DST) results. We quantified the second-line DST results time and proportion of patients potentially placed on suboptimal therapy. We included RR-tuberculosis patients detected using Xpert at the South African National Health Laboratory Services (NHLS) of the Western Cape between November 2011 and June 2013 and at Eastern Cape, Free State, and Gauteng NHLS between November 2012 and December 2013. We calculated time from specimen collection to phenotypic second-line DST results. We identified isoniazid and ethionamide resistance mutations on line probe assay and performed pyrazinamide sequencing. Among 1332 RR-tuberculosis patients, only 44.7% (596) had second-line DST for both fluoroquinolones and second-line injectable: 55.8% (466 of 835) in the Western Cape and 26.2% (130 of 497) in the other provinces. Patients with smear negative disease and age ≤10 years were less likely to have a result (risk ratio [RR] = 0.72; 95% CI, 0.64-0.81 and RR = 0.49; 95% CI, 0.26-0.79). Median time to second-line DST was 53 days (range, 8-259). Of the 252 patients with complete second-line DST, 101 (40.1%) potentially initiated a suboptimal regimen: 46.8% in the Western Cape and 25.3% in the other provinces. Many South Africans diagnosed with RR-tuberculosis by Xpert initiate a suboptimal regimen, with information to adjust therapy available in half of all patients after a median 7 weeks. Algorithm completion and time delays remain challenging.

Frequency of adverse events observed with second-line drugs among patients treated for multidrug-resistant tuberculosis

BackgroundMultidrug-resistant tuberculosis (MDR-TB) is considered to be a worldwide problem with notoriously difficult and challenging treatment. Adverse events associated with second-line drugs (SLDs) can have severe impact on efficient management. ObjectiveTo know the frequency of adverse events due to SLDs in patients of MDR-TB. DesignA prospective cohort analysis of 98 MDR-TB patients enrolled between June 2009 to February 2010 was conducted in Department of Pulmonary Medicine, King George Medical University, Lucknow, India. All the patients were provided standardized regimen. Adverse events associated with treatment were recognized primarily by clinical evidence and/or laboratory investigations that were advised at baseline and whenever clinically indicated during course of treatment. Adverse events were considered major if required permanent discontinuation or substitution of drugs. Results119 adverse events were reported in 46 (46.9%) patients. The grouped adverse events were most commonly gastrointestinal that was observed with a frequency of 48 (40.3%) followed by ototoxicity in 28 (23.6%), and neurological in 21 (17.6%). 17 (17.4%) patients had major adverse events requiring permanent discontinuation or substitution of drugs that included deafness and tinnitus in 5 (5.1%) followed by psychosis in 4 (4.1%). None of the patients stopped complete regimen due to adverse events. The treatment success rate was observed to be 71 (72.4%). ConclusionsMDR-TB can be cured successfully with appropriate combination of drugs if adverse events associated with them can be managed aggressively and timely. Newer and less toxic drugs are urgently needed to treat MDR-TB patients.

L’IRM est-elle utile dans le suivi des patients atteints de sclérose en plaques ? Non

Is regular MRI monitoring useful in clinical practice in multiple sclerosis patients treated with disease modifying therapy (DMT) drugs? My answer is no. Tacking a DMT drug is not by itself a pertinent criterion for requiring a systematic MRI monitoring in MS patients. Five clinical criteria should be taken into consideration before prescribing regular MRI examinations. The clinical form of the disease: MRI monitoring in DMT treated patients, has been demonstrated as useful only in pure relapsing-remitting MS patients. Up to now, there is no convincing demonstration of therapeutic efficacy with any DMT drug, neither first-line nor second-line drugs in patients with primary or secondary progressive MS disease. The duration of the disease, epidemiological data leading to the concept of a two-stage disability progression in MS, emphasizes the importance of treating as early as possible RRMS patients in order to stop accumulation of new focal MRI CNS lesions. In this regard, an annual monitoring for the 5 first years of the disease looks reasonable in order to better personalize the treatment choice among the few approved DMT drugs. The duration of the treatment: a first MRI assessment at month 6 after initiating a new DMT drug is adequate in order to better distinguish responder versus no responder. The persistence of Gado+lesions at 6 months is a strong indication for considering alternative treatment. The disease activity: both criteria, clinical and MRI, are needed to recognized very active or aggressive relapsing MS patients, leading to decide a rapid use of second-line treatment therapy. The treatment choice: in JC positive MS patients treated with natalizumab, the risk of PML is as high as more than 1 % in those JC+MS patients that are treated continuously more than 24months. A regular MRI monitoring (3 or 6months) is recommended in order to detect as early as possible MRI abnormalities suggesting PML.

Blood pressure lowering efficacy of potassium-sparing diuretics (that block the epithelial sodium channel) for primary hypertension.

Potassium-sparing diuretics, which block the epithelial sodium channel (ENaC), are widely prescribed for hypertension as a second-line drug in patients taking other diuretics (e.g. thiazide diuretics) and much less commonly prescribed as monotherapy. Therefore, it is essential to determine the effects of ENaC blockers on blood pressure (BP), heart rate and withdrawals due to adverse effects (WDAEs) when given as a first-line or second-line therapy. To quantify the dose-related reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) of ENaC blocker therapy as a first-line or second-line drug in patients with primary hypertension. We searched CENTRAL (The Cochrane Library 2012), MEDLINE (1950 to August 2012), EMBASE (1980 to August 2012) and reference lists of articles. Double-blind, randomized, controlled trials in patients with primary hypertension that evaluate, for a duration of 3 to 12 weeks, the BP lowering efficacy of: 1) fixed-dose monotherapy with an ENaC blocker compared with placebo; or 2) an ENaC blocker in combination with another class of anti-hypertensive drugs compared with the respective monotherapy (without an ENaC blocker). Two authors independently assessed the risk of bias and extracted data. Study authors were contacted for additional information. WDAE information was also collected from the trials. No trials evaluating the BP lowering efficacy of ENaC blockers as monotherapy in patients with primary hypertension were identified. Only 6 trials evaluated the BP lowering efficacy of low doses of amiloride and triamterene as a second drug in 496 participants with a baseline BP of 151/102 mm Hg. The additional BP reduction caused by the ENaC blocker as a second drug was estimated by comparing the difference in BP reduction between the combination and monotherapy groups. The addition of low doses of amiloride and triamterene in these trials did not reduce BP. An estimate of the dose-related BP lowering efficacy for ENaC blockers was not possible because of a lack of trial data at higher doses. ENaC blockers do not have a statistically or clinically significant BP lowering effect at low doses but trials at higher doses are not available. The review did not provide a good estimate of the incidence of harms associated with ENaC blockers.

A survey on resistance to second-line drugs in patients with pulmonary tuberculosis in Shanghai, China

To determine the pattern of resistance to second-line drugs (SLDs) in patients with tuberculosis (TB) in Shanghai, China. All sputum culture positive patients detected at each district/county TB hospital/clinic in Shanghai during January to December 2009 were enrolled. First-line drug susceptibility testing was routinely performed for each clinical isolate. All clinical isolates with any resistance to first-line anti-TB drug were tested for second-line drug susceptibility. Of the 431 TB patients with any resistance to first-line anti-TB drugs included in this study, 27.8% (120/431) were resistant to any SLDs tested. The rank of drug resistance was as follows: ofloxacin (68/431, 15.8%) > kanamycin (37/431, 8.6%) > para-aminosalicylic acid (35/431, 8.1%) > capreomycin (28/431, 6.5%) > amikacin (23/431, 5.3%) > prothionamide (8/431, 1.9%). Mono-resistance to SLD was the most predominant pattern. Among patients with resistance to SLD, the percentages of mono-resistance were 2/2, 20/36, 22/24 and 43/58 for rifampin-resistant group, isoniazid-resistant group, other-resistant group, and MDR group, respectively. The high prevalence of resistance to SLDs in TB patients suggests the necessity to strengthen the TB control program for drug-resistant TB in Shanghai.

Long Term Treatment Outcome In Multi Drug Resistant Tuberculosis(MDR-TB)

PURPOSE: Multidrug resistant tuberculosis (MDR-TB) is an increasing worldwide problem which is notoriously difficult to treat and has greater risk of relapse. Our study analyzes the longterm treatment outcome with second line drugs in patients with MDR-TB.

IgM-rheumatoid factor and responses to second-line drugs in rheumatoid arthritis

We have examined the relationship between IgM-rheumatoid factor (RF) and responses to second-line drugs in patients with rheumatoid arthritis (RA). Patients with active RA who were beginning treatment with gold, methotrexate or both were studied. Clinical responses were assessed with ESR, joint count, grip strength and activities of daily living questionnaire scores. Production of IgM-RF by peripheral blood mononuclear cells in vitro and plasma levels of IgM-RF were measured by ELISA. Overall, 31 of 44 patients completing more than 6 months treatment improved including 10 treated with gold, 12 with MTX and 9 with both. Production of IgM-RF by peripheral blood mononuclear cells was decreased by 59% in patients who improved on treatment, but increased 2-fold in the unimproved group. Plasma levels of IgM-RF were decreased from 121 to 66 micrograms/ml in the improved group after 6 months of treatment, with similar decreases seen for each of the three treatments. In contrast, plasma IgM-RF levels in the unimproved group did not decrease until 1 year of treatment was completed. Nine patients converted to seronegativity, and all but one of these were in the improved group. The results suggest that IgM-RF is correlated with responses to second-line drug in RA patients.

The Use of Second Line Drugs in Patients with Drug Resistance to Standard Tuberculostatics

Many patients with far-advanced cavitary pulmonary tuberculosis who had previous inadequate chemotherapy, harbor bacilli resistant to the standard drugs. Approximately 70 per cent of them harbor bacilli mainly resistant to two drugs, INH and SM. Proper choice of second line drug regimens should be based on detailed bacteriologic examination and sensitivity tests. Treatment should be started with a three-drug combination given in adequate dosage. The most often used combination given is ethionamide plus pyrazynamide plus cycloserine. After sputum conversion is achieved, a two-drug combination: ETA plus CS, or ETA plus PZA, is administered. Treatment should be started under institutional conditions and later continued on an ambulatory basis for one and one-half to two years, provided that the patient cooperates fully in his treatment. In our study, when these principles were followed, 92.4 per cent of sputum conversions were obtained after one year of treatment and 100 per cent of sputum conversion after one and one-half to two years of treatment. Among 25 patients who completed treatment of one and one-half year or longer, there were no relapses in the period of one to three years after drugs were discontinued. Unfortunately, about 35 per cent of patients stop their treatment due to side effects of the drugs or because they refuse treatment. In our overall study, about 65 per cent of patients were lost to treatment due to various reasons, the majority of them within the first year of treatment.