Showing posts with label Opioid Maintenance. Show all posts
Showing posts with label Opioid Maintenance. Show all posts

November 6, 2014

Maintenance Opioid Agonists Protect Against HCV in Injection Drug Users

Judith I. Tsui, MD, MPH1,2; Jennifer L. Evans, MS3; Paula J. Lum, MD, MPH4; Judith A. Hahn, PhD3,4; Kimberly Page, PhD, MPH5

[+-] Author Affiliations

1Clinical Addiction Research and Education Unit, Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
2Department of Medicine, Boston Medical Center, Boston, Massachusetts
3Department of Epidemiology and Biostatistics, University of California, San Francisco
4Department of Medicine, University of California, San Francisco
5Division of Epidemiology, Biostatistics and Preventive Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque

JAMA Intern Med. Published online October 27, 2014. doi:10.1001/jamainternmed.2014.5416

Abstract

Importance Injection drug use is the primary mode of transmission for hepatitis C virus (HCV) infection. Prior studies suggest opioid agonist therapy may reduce the incidence of HCV infection among injection drug users; however, little is known about the effects of this therapy in younger users.

Objective To evaluate whether opioid agonist therapy was associated with a lower incidence of HCV infection in a cohort of young adult injection drug users.

Design, Setting, and Participants Observational cohort study conducted from January 3, 2000, through August 21, 2013, with quarterly interviews and blood sampling. We recruited young adult (younger than 30 years) injection drug users who were negative for anti-HCV antibody and/or HCV RNA.

Exposures Substance use treatment within the past 3 months, including non–opioid agonist forms of treatment, opioid agonist (methadone hydrochloride or buprenorphine hydrochloride) detoxification or maintenance therapy, or no treatment.

Main Outcomes and Measures Incident HCV infection documented with a new positive result for HCV RNA and/or HCV antibodies. Cumulative incidence rates (95% CI) of HCV infection were calculated assuming a Poisson distribution. Cox proportional hazards regression models were fit adjusting for age, sex, race, years of injection drug use, homelessness, and incarceration.

Results Baseline characteristics of the sample (n = 552) included median age of 23 (interquartile range, 20-26) years; 31.9% female; 73.1% white; 39.7% who did not graduate from high school; and 69.2% who were homeless. During the observation period of 680 person-years, 171 incident cases of HCV infection occurred (incidence rate, 25.1 [95% CI, 21.6-29.2] per 100 person-years). The rate ratio was significantly lower for participants who reported recent maintenance opioid agonist therapy (0.31 [95% CI, 0.14-0.65]; P = .001) but not for those who reported recent non–opioid agonist forms of treatment (0.63 [95% CI, 0.37-1.08]; P = .09) or opioid agonist detoxification (1.45 [95% CI, 0.80-2.69]; P = .23). After adjustment for other covariates, maintenance opioid agonist therapy was associated with lower relative hazards for acquiring HCV infection over time (adjusted hazard ratio, 0.39 [95% CI, 0.18-0.87]; P = .02).

Conclusions and Relevance In this cohort of young adult injection drug users, recent maintenance opioid agonist therapy was associated with a lower incidence of HCV infection. Maintenance treatment with methadone or buprenorphine for opioid use disorders may be an important strategy to prevent the spread of HCV infection among young injection drug users.

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October 1, 2013

Hepatitis C treatment for multimorbid patients with substance use disorder in a primary care-based integrated treatment centre: a retrospective analysis

Eur J Gastroenterol Hepatol. 2013 Nov;25(11):1300-7. doi: 10.1097/MEG.0b013e32836140bb.

Brunner N, Senn O, Rosemann T, Falcato L, Bruggmann P.

aDepartment of Research, Institute of General Practice and Health Services, University of Zurich bDepartment of Internal Medicine, ARUD, Centres for Addiction Medicine, Zurich, Switzerland.

Abstract

OBJECTIVES/BACKGROUND: The population of people who use drugs (PWUD) has the highest prevalence of hepatitis C virus (HCV) infections in Europe. PWUD are multimorbid patients who are difficult to integrate into existing healthcare systems. In our study, we evaluated the feasibility of providing HCV treatment within opioid maintenance treatment (OMT) programmes offering integrated primary care-based health services under one roof.

METHODS: We evaluated 66 charts of patients in four outpatient clinics (OMT) with HCV treatment (between 2002 and 2010). Fourteen of the patients were treated with heroin and nine patients had an HIV coinfection. Data on the socioeconomic characteristics and quality of life were assessed. We counted the number of consultations in the clinic to assess how much supportive care the patients needed.

RESULTS: Overall, 62% of all patients (41 out of 66) achieved a sustained virological response (SVR). A total of 84% of patients with genotype 3 achieved an SVR. Sixty-four percent of patients treated with heroin achieved an SVR. The majority of patients (71%) used illicit drugs during HCV treatment and over 80% were diagnosed with psychiatric comorbidities. Comparisons of patient characteristics according to SVR or non-SVR showed that a longer duration of OMT, more consultations per week during HCV treatment and poor self-reported physical condition were associated with non-SVR.

CONCLUSION: We conclude that offering HCV treatment in an integrated primary care-based setting with OMT and individualized use of different supporting strategies allows for treatment success rates in the population of PWUD that is comparable to the ones in the population of patients without drug use. Heroin maintenance treatment programmes offer a feasible and safe setting for providing HCV treatment.

PMID: 23571610 [PubMed - in process]

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Pivotal Phase 3 Data from Boehringer Ingelheim Hepatitis C Portfolio to be Presented at 64th Annual AASLD Meeting

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October 01, 2013

For U.S. Media Only

Ridgefield, CT, October 1, 2013 New data from Boehringer Ingelheim’s hepatitis C virus (HCV) clinical development program have been accepted for presentation at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), also known as The Liver Meeting®, taking place November 1-5 in Washington, D.C.

Presentations will include data from several studies evaluating Boehringer Ingelheim’s investigational compound, faldaprevir, including final results from the STARTVerso 1, 2 and 3 pivotal trial programs (NCT01343888, NCT01297270, NCT01358864) in treatment-naïve and treatment-experienced patients. End-of-treatment results from STARTVerso 4™ (NCT01399619) evaluating HIV/HCV co-infected patients will also be presented.

Additionally, data will be presented from studies evaluating drug-drug interactions of faldaprevir with common birth control and anti-addiction medications, as well as a study evaluating faldaprevir pharmacokinetics, safety, and tolerability in patients with renal impairment. Final results from SOUND-C3 (NCT01132313), a Phase 2b study from Boehringer Ingelheim’s interferon-free development program, will also be presented.

Together these studies explore the use of Boehringer Ingelheim’s investigational HCV compounds in a broad range of patients with HCV, in addition to helping understand the potential for interactions with several commonly used medications. Also, they offer insight into the clinical profile of the compounds for researchers and healthcare professionals looking for potential new treatment options for patients with HCV.

“We are pleased to see the presentation of the final results from STARTVerso 1, 2 and 3, Boehringer Ingelheim’s pivotal Phase 3 program in our hepatitis C portfolio, as well as other important analyses evaluating various patient subgroups at this year’s AASLD meeting,” said Peter Piliero, M.D., Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “These data, combined with that of our interferon-free trial, SOUND-C3, are evidence of our commitment to researching new therapeutic options for patients infected with HCV.”

Faldaprevir and deleobuvir are investigational compounds and not approved by the FDA. Their safety and efficacy have not been established.

Boehringer Ingelheim’s abstracts can be accessed on the AASLD website today at www.aasld.org.

Poster Presentations

 

Title Lead Author Presentation Details
Effect of multiple oral doses of faldaprevir on the multiple dose pharmacokinetics of a combination oral tablet of ethinylestradiol and levonorgestrel in healthy premenopausal female volunteers J. Sabo ID# 482

Session: HCV Therapy: The Developmental Pipeline

Date: Sat, Nov. 2
Time: 2:00 PM – 7:30 PM ET
Location: Poster Hall
Mass balance, metabolic profile and the role of hepatic and bacterial enzymes in the metabolism of the HCV polymerase inhibitor, deleobuvir (BI 207127) R. Sane ID# 491

Session: HCV Therapy: The Developmental Pipeline

Date: Sat, Nov. 2
Time: 2:00 PM – 7:30 PM ET
Location: Poster Hall
Pharmacokinetics, safety, and tolerability of faldaprevir in patients with different levels of renal impairment F. Huang

ID# 466

Session: HCV Therapy: The Developmental Pipeline

 

Date: Sat, Nov. 2
Time: 2:00 PM – 7:30 PM ET
Location: Poster Hall

Effect of steady-state faldaprevir on the pharmacokinetics of steady-state methadone and buprenorphine/naloxone in subjects on stable addiction management therapy D. Joseph ID# 483

Session: HCV Therapy: The Developmental Pipeline

Date: Sat, Nov. 2
Time: 2:00 PM – 7:30 PM ET
Location: Poster Hall
A pooled analysis of two randomized, double-blind placebo-controlled Phase III trials (STARTVerso1&2) of faldaprevir plus pegylated interferon alfa-2a and ribavirin in treatment-naïve patients with chronic hepatitis C genotype-1 infection D. Jensen ID# 1088

Session: HCV Therapeutics: New Agents

Date: Sun, Nov. 3
Time: 8:00 AM – 5:30 PM ET
Location: Poster Hall
Subgroup analyses and baseline predictors of response with faldaprevir plus pegylated interferon alfa-2a and ribavirin in treatment-naïve patients with chronic hepatitis C genotype-1 infection: a pooled analysis of STARTVerso1 and 2 E.M. Yoshida

ID# 1114

 

Session: HCV Therapeutics: New Agents

 

Date: Sun, Nov. 3

Time: 8:00 AM – 5:30 PM ET
Location: Poster Hall

STARTVerso3: A randomized, double-blind, placebo-controlled Phase III trial of faldaprevir in combination with pegylated interferon alfa-2a and ribavirin in treatment-experienced patients with chronic hepatitis C genotype-1 infection I. Jacobson

ID# 1100

 

Session: HCV Therapeutics: New Agents

 

Date: Sun, Nov. 3
Time: 8:00 AM – 5:30 PM ET
Location: Poster Hall

Interferon-Free Treatment with Faldaprevir, Deleobuvir (BI 207127) and Ribavirin in SOUND-C3: 95% SVR12 in HCV-GT1b J.F. Dufour

ID# 1102

 

Session: HCV Therapeutics: New Agents

 

Date: Sun, Nov. 3
Time: 8:00 AM – 5:30 PM ET
Location: Poster Hall

STARTVerso 4 Phase III trial of faldaprevir plus peg interferon alfa-2a and ribavirin (PR) in patients with HIV and HCV genotype 1 coinfection: end of treatment response J. Rockstroh

ID# 1099

 

Session: HCV Therapeutics: New Agents

Date: Sun, Nov. 3
Time: 8:00 AM – 5:30 PM ET
Location: Poster Hall

Pharmacokinetic interactions of Faldaprevir and Deleobuvir (BI 207127) and their individual and combined effect on selected cytochrome P450 (CYP) probe substrates in genotype 1 hepatitis C infected patients

C. Cooper

ID# 1083

 

Session: HCV Therapeutics: New Agents

 

Date: Sun, Nov. 3
Time: 8:00 AM – 5:30 PM ET
Location: Poster Hall

About Boehringer Ingelheim in Hepatitis C Virus (HCV)
In partnership with the scientific community, our clinical trial program is rigorously designed to find answers to the challenges that HCV patients face, including those who are the most difficult to treat. Our pivotal HCV clinical trials for faldaprevir and deleobuvir are comprised of two multi-trial programs, STARTVerso and HCVerso®.

Faldaprevir, also known as BI 201335, is an investigational, oral protease inhibitor that is specifically designed to target viral replication in the liver. Boehringer Ingelheim is developing faldaprevir as a core component of both interferon-based and interferon-free hepatitis C treatment regimens. STARTVerso is a multi-study Phase 3 trial program that evaluates faldaprevir combined with PegIFN/RBV. The four trials that make up this program study the combination in treatment-naïve, treatment-experienced and HIV co-infected patients with chronic genotype-1 HCV. Deleobuvir, also known as BI 207127, is an investigational NS5B non-nucleoside polymerase inhibitor that has shown the potential to eliminate interferon from HCV treatment when combined in a regimen with faldaprevir and RBV. Phase 2 trials of this interferon-free regimen have been completed and Phase 3 HCVerso® trials investigating this regimen are now underway. As part of our long-term commitment to HCV, the company is exploring other combinations of investigational HCV compounds that work in complementary ways. The recent collaboration of Boehringer Ingelheim with Presidio Pharmaceuticals, Inc. for a Phase 2a clinical study investigating an interferon- and ribavirin-free, all-oral combination is part of the company’s continued commitment to discover and develop innovative options for the treatment of HCV.

STARTVerso and HCVerso® are registered service marks of Boehringer Ingelheim International GmbH.

The Liver Meeting® is a registered trademark of the American Association for the Study of Liver Diseases (AASLD).

Hepatitis C is a blood-born infectious disease and a leading cause of chronic liver disease, transplant and failure that affects as many as 150 million people globally. In the United States, an estimated 4.1 million Americans have been infected with HCV, of which approximately 3.2 million have chronic HCV infection. Since 1999 there has been a significant increase in deaths due to chronic HCV, which accounts for 10,000-12,000 deaths in the United States per year.

About Boehringer Ingelheim
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

Social responsibility is a central element of Boehringer Ingelheim’s culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

For more information please visit www.us.boehringer-ingelheim.com

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May 12, 2013

Now the Tough Part

Provided by PsychCentral.com

An Epidemic of Addiction Blog

By J.T. Junig,  MD, PhD

The forces of nature appear intent on reversing mankind’s progress toward better health. An example is the ever-increasing resistance of bacteria to antibiotics. A timeline of the existence of humans and bacteria shows that bacteria have been around for a very long time— much longer than mammals, and much, much longer than humans. In fact by the dawn mankind, bacteria had been thriving, relatively uninhibited, for over 2 billion years.

Modern humans have been around for 40,000-200,000 years or so, depending on the definition of ’modern.’ Bacteria have had the upper hand during all of mans’ existence, save for the past 100 years after penicillin and other antibiotics were discovered. Only the most self-centered of species would look at a timeline and conclude that humans have won the battle with bacterial diseases. There are always reasons for optimism, but a fair assessment of our current struggle with antibiotic resistance suggests that someday, people will look back on the current sliver of time, when humans can treat most bacterial infections, as a golden era of medicine that wasn’t appreciated as such at the time.

Viruses adapt to mankind’s health efforts too, with new variants arising from the sludge at the bottom of the food chain to infect birds, swine, or other creatures before moving on to human hosts. The CDC and other scientists work to predict the vulnerabilities of the next super-virus, hoping to reduce the severity of the next pandemic. As with bacteria, we are enjoying an era without smallpox, polio, or other dreaded viral diseases that used to kill otherwise-healthy people. We take the victor’s position for granted to the point that our children don’t know why chlorine was first added to swimming pools. Gone with the last generation are the fears associated with iron lungs, orange window-signs, and leg braces.

Even the Human Immunodeficiency Virus, an agent of certain death in the 1980’s was transformed into a chronic, treatable illness. I was new to medicine when ‘universal precautions’ were first instituted (can our children even imagine having their teeth examined by someone not wearing latex gloves?!) Researchers don’t celebrate, though, since medication-resistant strains of HIV were expected to emerge– and have emerged.

As a medical student I learned about ‘non-A non-B hepatitis’, a small concern at the time that has since grown into the identity of ‘Hep C’ (Funny how long it took to come up with THAT name!) Hepatitis C is a major public health threat, since routine vaccinations for hepatitis B and the surge in IV drug use.

Not all diseases are from non-human entities. Cancers, for example, arise from errors in our own DNA, either inherited or acquired. Cures have been found for a few cancers, but like bacteria, cancers have emerged that are resistant to current chemotherapeutic drugs, requiring a constant search for new agents.

Some illnesses are considered ‘lifestyle diseases’ because they are related to obesity, smoking, pollution, substance use, inactivity, or poor diet— such as hypertension, heart disease, diabetes, cerebrovascular disease, asthma, and COPD. The model of resistance show by bacteria doesn’t fit in the same way, but many of these illnesses draw public attention as ‘epidemics’ that demand resources, with apathy or cultural phenomena function acting as resistance to those efforts.

Bear with me; I’m working up to something that I’ve alluded to before. My point is that like with other illnesses, addiction doesn’t respond to medications– Suboxone and buprenorphine — quite the way it used to.

When Suboxone hit the US market in 2003, large numbers of opioid addicts were scattered across the country, sick and tired of their dependence on opioids. Heroin was considered a ‘bad drug’ back then even by those with severe addictions, and was rarely encountered by teens and young adults. Most opioid addicts used hydrocodone or oxycodone, prescribed by doctors or obtained from people with prescriptions. Heroin was marginalized to those with the most-severe addictions, or used sporadically in combination with other drugs (e.g. speedballing). Known doses of oxycodone were comparatively safer than heroin, which is stepped on to varying amounts and sometimes laced with deadly fentanyl. Oxycodone was absorbed through mucous membranes more quickly than heroin, meaning lower motivation to use needles. So in the early 2000’s, some people addicted to opioids found a way to get by, albeit in state of chronic misery and loneliness after spouses and friends moved away.

Enter Suboxone– a new medication to treat opioid dependence. Suboxone carried some controversy, as some in the non-medication treatment lobby did their best to tarnish the medication (as in ‘you’re not as clean as I am!). But despite the tarnish, Suboxone and buprenorphine were medications that were to be prescribed by doctors. People who for years kept the same horrible secret were given an option that actually worked. People returning to my office for follow-up had tears of happiness on their faces; they thought they would never be free from their afflictions, and were grateful as Hell for a chance to return to the living.

Many of those patients have done well for years, in treatment in my practice and others. Many are still on buprenorphine and grateful to be on buprenorphine, as happy and productive as they’ve ever been in life, with no desire to change.

But then, just as some of us were becoming optimistic about this great new medication, the disease of addiction changed in the direction that all diseases change– for the worse. The substrate changed; oxycodone was largely removed from the market through well-intentioned anti-diversion efforts that made Oxycontin harder to abuse… just as the US experienced a large influx of cheap heroin. And as in the 1960′s, heroin brought out needles– something that many opioid addicts used to take pride in for not considering.

And Suboxone changed. People on buprenorphine or Suboxone sometimes shared a bit of their medication with friends going through dry spells. Some people on Suboxone or buprenorphine sold portions of their prescriptions. The image of Suboxone held by active heroin addicts changed from doctor’s medication to a self-directed treatment for withdrawal. In fact, the perceived roles of patient vs. treatment provider became blurred by needle exchange programs and programs that provide addicts with syringes loaded with naloxone. Against a confusing backdrop of publicly-provided needles, free syringes pre-loaded with naloxone, and expensive brand film vs. affordable generic buprenorphine, the image of Suboxone turned from orange to gray.

I don’t mean to criticize the well-intentioned efforts to save lives, such as the distribution of naloxone in areas where overdoses have become epidemic. It’s hard to predict unintended consequences. But now, new patients consist of 18-y-o heroin addicts who see Suboxone as a tool to provide cover for a few days, when the heroin supply runs dry. Some see Suboxone as a tool to detox, although the detoxes never accomplish anything at all—the ultimate bridge to nowhere. The bottom line is that after seeing a few Suboxone tablets ground up, dissolved, cooked, and injected, the medication loses a bit of luster.

And finally, patients themselves have changed. Opioid addicts in 2013 are often acutely ill from unknown doses, toxic fillers, and dirty needles, presenting to ER’s with antecubital abscesses and hepatitis C. And despite being very, very sick, many haven’t had enough time to get sick and TIRED. Being started on Suboxone is less of a bit deal because they’ve BEEN on Suboxone— little chips of it, over and over and over, whenever the heroin ran out.

Gone are the easy buprenorphine patients. Now we have young, fresh, sick addicts who won’t live long enough to hate their addictions. Addiction as a disease has adapted to our treatment efforts, and become stronger– and deadlier. Our side had better keep up the hard work.

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January 8, 2013

Patients receiving opioid maintenance treatment in primary care: successful chronic hepatitis C care in a real world setting

Published on: 2013-01-08

Injection drug users (IDUs) represent a significant proportion of patients with chronic hepatitis C (CHC). The low treatment uptake among these patients results in a low treatment effectiveness and a limited public health impact.

We hypothesised that a general practitioner (GP) providing an opioid maintenance treatment (OMT) for addicted patients can achieve CHC treatment and sustained virological response rates (SVR) comparable to patients without drug dependency.

Methods: Retrospective patient record analysis of 85 CHC patients who received OMT for more than 3 months in a single-handed general practice in Zurich from January 1, 2002 through May 31, 2008. CHC treatment was based on a combination with pegylated interferon and ribavirin.

Treatment uptake and SVR (undetectable HCV RNA 6 months after end of treatment) were assessed. The association between treatment uptake and patient characteristics was investigated by multiple logistic regression.

Results: In 35 out of 85 CHC patients (52 males) with a median (IQR) age of 38.8 (35.0-44.4) years, antiviral therapy was started (41.2%).

Median duration (IQR) of OMT in the treatment group was 55.0 (35.0-110.1) months compared to the group without therapy 24.0 (9.8-46.3) months) (p<0.001). OMT duration remained a significant determinant for treatment uptake when controlled for potential confounding.
SVR was achieved in 25 out of 35 patients (71%).

Conclusion: In addicted patients a high CHC treatment and viral eradication rate in a primary care setting in Switzerland is feasible. Opioid substitution seems a beneficial framework for CHC care in this "difficult to treat"population.

Author: André SeidenbergThomas RosemannOliver Senn

Credits/Source: BMC Infectious Diseases 2013, 13:9

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