Kirandeep Kaur

Systematic review of tofacitinib: a new drug for the management of rheumatoid arthritis.

PURPOSE The goal of this study was to review and summarize the efficacy and safety of use of tofacitinib for treating rheumatoid arthritis (RA). METHODS A systematic literature review was conducted to identify English-language articles published through May 2013 within PubMed, ClinicalTrials.gov, and Cochrane Library reporting results from Phase II and Phase III tofacitinib randomized clinical trials. Tofacitinib must have been used as monotherapy or in combination therapy with disease-modifying antirheumatic drugs (DMARDs) in the treatment of RA. Study outcomes had to include at least 1 of the following: American College of Rheumatology (ACR) 20%, 50%, or 70% response rates; tender/swollen joint count; health assessment questionnaire of disability; radiographic outcomes; and drug persistence. FINDINGS Eight studies (4 Phase II and 4 Phase III trials) were included in the review. Patients with active RA and who were nonresponders to a biologic agent or the nonbiologic DMARD methotrexate were included in these studies. The results of the Phase II trials show that tofacitinib at doses ≥3 mg BID was efficacious among the nonresponders. The results of the Phase III trials, comparing tofacitinib 5 and 10 mg with placebo, show that tofacitinib led to a significant improvement in ACR20 response (P < 0.0001), Health Assessment Questionnaire-Disability Index (P < 0.0001) scores, and ACR50 response (P < 0.0001) after 3 months. The efficacy of tofacitinib was numerically similar to adalimumab. The most common adverse events were infections, infestations, increases in LDL-C and HDL-C levels, and a decrease in neutrophil counts. IMPLICATIONS Tofacitinib is an efficacious drug for the management of moderate to severe RA among patients with an inadequate response to methotrexate and tumor necrosis factor inhibitors. Long-term studies can help in understanding the risk/benefit profile of tofacitinib.

Varenicline for Smoking Cessation: A Review of the Literature

BACKGROUND Smoking is the leading preventable risk to human health. Various agents have been used to promote smoking cessation, but none has had long-term efficacy. Varenicline, a new nicotinic ligand based on the structure of cytosine, was approved by the US Food amd Drug Administration for use as a smoking cessation aid. OBJECTIVES The aims of this review were to provide an overview on the mechanism of action and preclinical and clinical data of the new drug, varenicline, and to discuss the current and future impact of varenicline as a treatment for smoking cessation. METHODS MEDLINE, BIOSIS, and Google scholar databases were searched (March 1, 2007-July 1, 2008) using the terms varenicline, smoking cessation, and nicotinic receptors. Full-text articles in English were selected for reference, and articles presenting the mechanism of action, pharmacokinetics, and data from preclinical and clinical trials were included. RESULTS The initial literature search yielded 70 papers. A total of 20 articles fulfilled the inclusion criteria. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, inhibits dopaminergic activation produced by smoking and decreases the craving and withdrawal syndrome that accompanies cessation attempts. In Phase III clinical trials, the carbon monoxide-confirmed 4-week continuous abstinence rates were significantly higher with varenicline than with buproprion sustained release or placebo for weeks 9 through 12. Varenicline has been found to be well tolerated, with nausea being the most commonly reported (28.1%) adverse event. CONCLUSIONS Varenicline is the first drug for smoking cessation that has been found to have significant effectiveness in long-term relapse prevention (up to 52 weeks). Varenicline, with its unique profile of agonist and antagonist properties, increased cessation rates (both short- and long-term) compared with both placebo and bupropion sustained release.

Fesoterodine for Overactive Bladder: A Review of the Literature

BACKGROUND Overactive bladder (OAB) is a chronic condition affecting both men and women, with prevalence increasing with age. Antimuscarinics form the cornerstone of treatment of OAB. Fesoterodine, a nonselective muscarinic-receptor antagonist, was approved by the US Food and Drug Administration in late 2008 for once daily, oral administration in the treatment of OAB to relieve the symptoms of urinary urge incontinence, urgency, and frequency. OBJECTIVE The aim of this review was to provide an overview of the mechanism of action of and clinical trial data for fesoterodine, and to discuss the present status of fesoterodine in the management of OAB. METHODS The MEDLINE and Google Scholar databases were searched (June 1, 1999-December 1, 2009) using the terms fesoterodine, overactive bladder, and muscarinic antagonists. Full-text articles in English were selected for reference, and articles presenting the mechanism of action, pharmacokinetics, and data from clinical trials were included. The parameters measured were tolerability, efficacy, and health-related quality of life (HRQoL). Trials involving animals and Phase I studies were excluded. RESULTS The initial literature search yielded 48 papers. A total of 20 articles fulfilled the inclusion criteria. In two 12-week, randomized, multicenter, Phase III clinical trials involving patients with increased micturition frequency and urgency and/or urinary urge incontinence (n = 836 and 1132 in each trial), both fesoterodine 4 and 8 mg were associated with significantly improved symptoms of OAB (frequency of micturition, urgency, and urge incontinence) compared with placebo (P < 0.05). In a post hoc analysis of pooled data of the Phase III trials, HRQoL improved significantly with both doses. In a 12-week, Phase Illb trial, fesoterodine 4 and 8 mg led to treatment satisfaction in ∼80% of patients (of 516 enrolled) who were initially unsatisfied with their previous treatment. CONCLUSION A review of the literature suggests that fesoterodine is an efficacious and well-tolerated treatment option for patients with OAB.

Clinical profile of hepatitis C virus infection in a developing country- India

The epidemiology and clinical profile of hepatitis C virus (HCV) varies worldwide, and data from developing countries are sparse. The aim of the present study was to assess the clinical profile of HCV infection in a developing country in South‐East Asia (India).

An open-label comparison of the effects of simvastatin and niacin alone and combined on the lipid profile and lipoprotein (a) level in an Indian population with dyslipidemia.

UNLABELLED Abstract. BACKGROUND Patients with dyslipidemia often require the use of >1 lipid-altering agent to achieve the target levels recommended by the National Cholesterol Education Program Adult Treatment Panel III. OBJECTIVE The aim of this study was to compare the effects of simvastatin and niacin alone and combined on the lipid profile and lipoprotein (a) (Lp[a]) level in an Indian population with dyslipidemia. METHODS This 12-week, open-label, nonrandomized study was conducted at the Departments of Pharmacology and Medicine, Government Medical College, Amritsar (Punjab), India. Patients aged 30 to 70 years with dyslipidemia were eligible. Patients were assigned to 1 of 3 treatment groups. Group 1 received simvastatin 20 mg/d for 12 weeks. Group 2 received niacin at doses of 375 mg/d for 1 week, 500 mg/d for 1 week, and 500 mg BID for 10 weeks. Group 3 received simvastatin 10 mg/d plus niacin (375 mg for 1 week and 500 mg for 11 weeks). The lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and Lp(a) were measured before the start of therapy and at 6 and 12 weeks of treatment. Percentage changes from baseline were calculated. Adverse effects (AEs) were recorded at weeks 6 and 12 and through spontaneous reporting. RESULTS Ninety patients were enrolled (50 men, 40 women; 30 patients per treatment group). In group 1, the mean (SD) percentage decrease in LDL-C level at 12 weeks was 42.79% (16.29%) (P < 0.05), but no significant change was seen in group 2 or 3. The mean (SD) percentage increases in HDL-C level were 18.43% (13.28%) and 20.82% (17.57%) in groups 2 and 3, respectively (both, P < 0.05), but no significant change was seen in group 1. TC levels decreased by a mean (SD) of 32.97% (13.66%) in group 1 (P < 0.05), but no significant change was seen in group 2 or 3. TG and Lp(a) levels did not change significantly in any of the 3 treatment groups. Flushing, myalgia, and dyspepsia were the most common AEs in patients receiving niacin. CONCLUSIONS In this study in Indian patients with dyslipidemia, simvastatin-niacin combination therapy was associated with greater changes in lipid profile compared with either agent used alone. Niacin was also associated with greater changes in Lp(a) levels. AEs were less prevalent with combination therapy than with niacin alone.

Efficacy and safety of the adalimumab biosimilar Exemptia as induction therapy in moderate-to-severe ulcerative colitis

Background/Aims Data on the efficacy and safety of the adalimumab biosimilar Exemptia are limited. Methods Patients with moderate-to-severe active steroid-refractory ulcerative colitis (UC) treated at Dayanand Medical College and Hospital, India were offered cyclosporine A, biologicals or biosimilars, or surgery. A retrospective analysis was conducted on patients who were treated with the adalimumab biosimilar, Exemptia. These patients were administered an induction dosing schedule of 160 mg Exemptia at week 0, 80 mg at week 2, and then 40 mg every other week from week 4 to 8. The clinical response and remission were assessed at week 8 using Mayo score. Results A total of 29 patients (62.1% male; mean age, 34.9 ± 9.7 years) with moderate-to-severe steroid-refractory active UC (mean disease duration, 6.3±5.1 years; pancolitis in 9 patients [31.1%]; left-sided colitis in 20 patients [68.9%]) were treated with the Exemptia induction dosing schedule. The mean Mayo score at presentation was 8.2±1.4. At week 8, clinical response was observed in 7 patients (24.1%), whereas clinical remission was observed only in 1 patient (3.5%). Among the non-responders (n=21), 4 patients required colectomy, 1 died, 1 was lost to follow-up, 10 were offered fecal microbiota transplant, 3 were administered infliximab, and 2 patients were administered cyclosporine and tacrolimus, respectively. Four patients (13.8%) developed extrapulmonary tuberculosis. Conclusions The adalimumab biosimilar Exemptia has limited efficacy for the attainment of clinical response and remission in moderate-to-severe steroid-refractory UC, with a significant risk of acquisition or reactivation of tuberculosis in developing countries such as India.

A simple phenotypic classification for celiac disease

Background/Aims Celiac disease is a global health problem. The presentation of celiac disease has unfolded over years and it is now known that it can manifest at different ages, has varied presentations, and is prone to develop complications, if not managed properly. Although the Oslo definitions provide consensus on the various terminologies used in literature, there is no phenotypic classification providing a composite diagnosis for the disease. Methods Various variables identified for phenotypic classification included age at diagnosis, age at onset of symptoms, clinical presentation, family history and complications. These were applied to the existing registry of 1,664 patients at Dayanand Medical College and Hospital, Ludhiana, India. In addition, age was evaluated as below 15 and below 18 years. Cross tabulations were used for the verification of the classification using the existing data. Expert opinion was sought from both international and national experts of varying fields. Results After empirical verification, age at diagnosis was considered appropriate in between A1 (<18) and A2 (≥18). The disease presentation has been classified into 3 types–P1 (classical), P2 (non-classical) and P3 (asymptomatic). Complications were considered as absent (C0) or present (C1). A single phenotypic classification based on these 3 characteristics, namely age at the diagnosis, clinical presentation, and intestinal complications (APC classification) was derived. Conclusions APC classification (age at diagnosis, presentation, complications) is a simple disease explanatory classification for patients with celiac disease aimed at providing a composite diagnosis.

Symptomatic isolated terminal ileal ulcers: etiology and clinical significance

Background  With an increasing number of ileal intubations, isolated terminal ileal ulcers (ITIU) are frequently found during colonoscopies. The present study aimed at studying the etiology and clinical significance of these ulcers in patients having gastrointestinal symptoms. Methods  This was a prospective observational study performed on consecutive patients who underwent ileocolonoscopy for various gastrointestinal symptoms between 1 January 2014 and 31 December 2014. Clinical, endoscopic, and histological findings of patients with ITIUs were assessed to determine the etiology and they were treated accordingly. Symptom resolution was assessed within 3 – 6 months of initial diagnosis, and colonoscopy was repeated for consenting patients. Results  Among 74 (4.9 %) of 1497 patients who had ITIUs on ileocolonoscopy, 41 (55.4 %) had specific etiologies on initial testing. After 3 – 6 months follow-up, definitive diagnosis was ascertained in 44 (59.5 %) patients [Crohn’s disease (CD): 19 (25.7 %), NSAID-induced ulcers: 11 (14.9 %), intestinal tuberculosis (ITB): 9 (12.2 %), and eosinophilic enteritis: 5 (6.8 %)], and 30 patients (40.5 %) had nonspecific ulcers. After treatment, symptomatic and endoscopic resolution were noted in 55/60 patients (91.7 %) and 28/36 patients (77.8 %), respectively. Of 5/60 patients who remained symptomatic, three were initially diagnosed with nonspecific ulcers and two with CD, and they were finally diagnosed with CD and ITB respectively, and treated accordingly. Conclusions  In patients with gastrointestinal symptoms, more than half of the ITIUs have specific etiologies, and timely diagnosis and appropriate treatment can prevent serious complications. Nonspecific ulcers can be managed with symptomatic treatment, but need close monitoring and re-evaluation in the case of persistence of symptoms.