Кой интерферон да избера за лечението ми - Пегасис или Пегинтрон?

[mitko chi]

Здравейте всички,
Вчера най-после успях да видя доктора си за първи път след биопсията ми.В началото той ми каза, както и преди по телефона,че понеже съм с мин. увреждане иска да се изчака 3-4 год.и да се направи нова биопсия и ако вече съм в 2-ра степен на фиброза да се започне лечение. Аз използвах всички доводи за които се сетих, в полза на по-ранното лечение (не че той не ги знае) в крайна сметка успях да го накарам да се съгласи да започнем лечение.
Видях си и последните ми изследвания от 29-11-07. От тях ALT ми се качил на 77 U/L и total bilirubin ми е 1,4 mg/ml.
Докато през август ми бяха в норма. Сега ми пусна доста тестове вкл.и ПСР (също и за croyglobonemia той се съмнява, че имам и това заболяване кожния доктор, при който ходих ми каза, че е Lichen planes,свързано е също с хепатита).
Доктора предпочита PEGASYS пред PEG-INTRON. Даде ми тел на Roche да се обадя за безплатни лекарства, защото нямам здравна застраховка. Ако оттам не става, ще пробвам с Schering.
Той смята, че пегасиса е с по-малко странични ефекти и май че и аз видях такава инфо в нета, но като че ли пък пегинтрона е по-ефикасен при генотип 1. Разбира се никой не твърди такова нещо със сигурност, защото става дума за много пари. Значи аз сега разбрах, че една от основните разлики е, че при пегасиса дозата е една и съща т.е. не зависи от теглото май, има две категории тегло,а при пегинтрона се определя от теглото т.е.мг/кг тегло. Мненията на различните доктори са различни, повечето като, че ли смятат че не от голямо значение.Аз обаче искам да си изградя собствено мнение за сега съм още объркан. Ето сега ще пусна нещо по въпроса

Chronic Hepatitis C

By Liz Highleyman

http://www.hivandhepatitis.com/hep_c/news/2006/072506_a.html

A recent Argentine study published in the August 2006 Journal of Hepatology compared the pharmacokinetics, pharmacodynamics, and antiviral activity of the two approved brands of pegylated interferon -- Pegasys (pegylated interferon alfa-2a) and Peg-Intron (pegylated interferon alfa-2b) -- in 36 patients with genotype 1 chronic hepatitis C.

The researchers found that patients receiving Peg-Intron had significantly greater decreases in HCV viral load and a greater likelihood of achieving a 2-log reduction in HCV RNA by week 8 (72% vs 44%; P = 0.09), even though patients receiving Pegasys had higher plasma levels of the drug.
They therefore concluded that, “These findings suggest that the biological activity, measured by early interferon-induced gene transcripts and early antiviral responsiveness, may have been greater in patients treated with [Peg-Intron], despite their lower exposure to the drug compared with patients treated with [Pegasys].”

In an accompanying editorial in the same issue, however, hepatologists Peter Jansen, MD, and Henk Reesink, MD, urged caution about reaching premature conclusions as to which form of pegylated interferon is superior.

The authors noted that Pegasys is a more bulky branched molecule than Peg-Intron; Pegasys has a molecular mass of 40 kilodaltons (kDa), compared with 12 kDa for Peg-Intron. In general, they noted, Peg-Intron has a larger volume of distribution and higher renal clearance than Pegasys. Typically, Peg-Intron is dosed based on body weight, while Pegasys is administered as a flat dose.

Reviewing studies to date, they wrote that, “In terms of efficacy the books are still open. ”Many factors contribute to a treatment’s effectiveness, including drug-receptor interactions, maximum serum concentrations, trough levels, volume of distribution, and areas under the serum-concentration curve.

Jansen and Reesink noted that neutral head-to-head comparisons are the best way to determine the relative efficacy of different treatments, but such trials are expensive and difficult to conduct without industry sponsorship.

“To set up a study in a neutral environment, that is fair to both comparators, is difficult enough, to organize a fair study sponsored by companies, with shareholders looking over their shoulders, is doubly difficult,” they wrote. “Not only shareholders are looking on but also governments that ideally want to reimburse only one drug per indication. Therefore these studies have to be scrutinized to find out if science wins over economy.

”Small studies to date have provided conflicting results. The 36-person Argentine trial, sponsored by Shering-Plough (the manufacturer of Peg-Intron), found that 8-week treatment with weight-based Peg-Intron appeared to work better than fixed-dose Pegasys. Another small trial sponsored by Roche (the manufacturer of Pegasys), found that the drugs yielded similar response rates after 8 weeks of therapy. The Argentine study also found that Peg-Intron led to greater up-regulation of interferon-alfa response genes, but it remains unclear how the activity of these genes relates to sustained response to interferon therapy.

In the end, Jansen and Reesink emphasized, “it is the sustained viral response (SVR, the viral level 6 months after stopping the drug treatment) that really counts.” Response at 12 weeks is also useful, since patients who do not respond at this point can choose to stop treatment, thereby avoiding side effects and reducing cost. A larger study called IDEAL (also sponsored by Shering-Plough) is scheduled to report comparative SVR results in the first half of 2007.

“In view of the more than 175 million patients who are infected with HCV, the stakes for the industry are high,” the authors concluded. “We as hepatologists should not be too naïve in thinking that these comparison trials are designed and conducted by the industry for purely scientific reasons. For the industry these trials are, economically speaking, life or death. We should continue to make sense of the data and we should not decide too quickly that one drug is better than the other.

8/8/06

”Reference

P L M Jansen and H W Reesink. Antiviral effect of peginterferon alfa-2b and alfa-2a compared. Journal of Hepatology 45(2): 172-173. August 2006.

това е от сайта www.hivandhepatitis.com

Искам да попитам всички с генотип 1 б, които са преминали лечение са на лечение или ще започват и знаят с кои интерферон какъв вид инт.са използвали, и как са взели решение кой вид да използват.
Чао за сега!

П.П. Моля кажете си мнението, мисля че този избор е доста важен!

[Радослав Русинов]

Здравей Митко,
Никой не може и няма как да ти даде еднозначен отговор на този въпрос. Ако си в България, единственото лекарство, за което можеш да чуеш, е Пегасис.
Чел съм и мисля, че в момента все още тече най-голямото изследване правено досега, което прави сравнение между двата интерферона. Може и да е завършило обаче, трябва да се поровиш в интернет. Но според мен още не са излезли резултатите, иначе щеше да се чуе.
Значи двете лекарства се основават на интерферон, но всъщност на молекулярно ниво са различни.
Ето един цитат от интервю на проф. Чернев, което е свързано с темата:

Бяхме на европейско ниво, а се връщаме една ера назад
...
- Искате да кажете, че лекарство, което не върши работа на специалистите, може да бъде одобрено за лечение?
- Може да бъде одобрено, разбира се. Ако обаче става дума дали аспиринът да бъде френски или американски, решението не е така фатално. Химическата формула на аспирина е проста и кой от двата ще изберем няма особено значение. Докато, когато става дума за молекулярно биологичен препарат какъвто е интерферонът, има огромно значение кой е производителят, как точно се произвежда и какви са неговите качества.
...

Това изказване е достатъчно показателно, компанията-производител единствено знае формулата по която се произвежда лекарството и всеки интерферон е различен. Относно това, че Пегинтрон е по-ефикасен при генотип 1, също няма доказтелство за това твърдение.
Изследването, което цитираш просто твърди, че пациентите, които се лекуват с Пегинтрон имат по-голям шанс вируса да не се засича още на 8-та седмица на лечението, за разлика от Пегасис, при който се постигало на 12-тата седмица.
Аз поне не бих могъл да ти дам съвет, но поне доколкото виждам дори и на запад, Пегасис е по-често използван. Дали това е свързано с лобиране или с повишена ефективност, ми е трудно да кажа - в крайна сметка това никой не може да го каже.
Фармацевтичните компании са вложили милиарди в разработките си и винаги, когато са замесени толкова пари, никой не може да  е напълно наясно какво точно се случва.

Поздрави,
Радо

[nevron]

Здравейте!
Аз получавам последните новости и резултати от анализи, експерименти и пр. проучвания около хепатитите на личната си електронна поща. Мисля, че преди 2-3 седмици получих някаква информация свързана със сравнение между двата вида интерферони и тяхното значение, приложение и активност, но тъй като съм зодия дева и не мога да разхвърлям и нахвърлям информацията немърливо и неточно подредена, ще го направя най-много до два-три дни прилежно написано и добре преведено в някой от разделите за статии или обща информация, или може би директно в тази тема.
Извини ме Митко, че няма да е веднага, но просто и нямям достатъчно време да свърша тази работа на момента, колкото и да ми се иска. Статията не е много кратка и за това ще го оставя за утре или най-късно в други ден.
Ок?
Поздрави!

П.П. Като цяло ми се струва, че положителни бяха отзивите за Пегасис-а.

[Stefan Savov]

Неврон-ка, по една случайност съм професионален преводач с местен и чуждестранен опит, софтуер, речници и пр. Ако имаш нужда от съдействие, не се колебай да ми пишеш на мейла или тук във форума - ще помогна безкористно и приоритетно.

[nevron]

ОК, Стефчо!
Тук ще постна страницата с най-новите статии свързани с хепатитите.

http://hepato.com/esp_novaentrada.html

Това е страницата с всички статии.

http://www.hepato.com/p_resposta_ao_tratamento/ideal_resp_roche_20080129.html#esp

Това е статията свързана със запитването в тази тема.

http://www.hepato.com/p_biopsia/fibroscan_20080211.html#esp

Това е статия, свързана с нов метод за определяне степента на увреждане без биопсия, а чрез нов метод подобен на ехографията.

Поздрави!
Изчезвам, че ме чакат.

[Stefan Savov]

Оценявам иронията, няма да се изказвам повече толкова прибързано. Преводач съм от и на английски език.

[Радослав Русинов]

Митко, ето за това изследване говорих, инициирано е от Schering и се нарича IDEAL /Individualized Dosing Efficacy vs. Flat Dosing to Assess optimal pegylated interferon therapy/, резултатите от което са публикувани през януари 2008 и са правени, за да докажат дали е правилно да се прави различна дозировка в зависимост от килограмите: IDEAL Trial Results

IDEAL Trial Results

Alan Franciscus, Editor-in-Chief

 The IDEAL (Individualized Dosing Efficacy vs. Flat Dosing to Assess optimal pegylated interferon therapy) clinical trial results were released by Schering in January 2008.  The trial was a Food & Drug Administration (FDA) mandated clinical trial to find out what dose of Peg-Intron (1.5 mcg/kg/week vs. 1.0 mcg/kg/week) is the most effective for the treatment of hepatitis C when combined with ribavirin.  In the study design Schering added an arm to compare the effectiveness of Peg-Intron (plus ribavirin) with Pegasys (plus ribavirin).  This part of the trial has been promoted as a head-to-head study of the two pegylated interferons, but as I will discuss later in this article it is not a true head-to-head study because the study design was flawed. 

There were 3,070 treatment naïve HCV genotype 1 patients enrolled in the study throughout the United States who were randomized into three different treatment arms:

    * Group A:  Peg-Intron: 1.5 mcg/kg/week and Rebetol (ribavirin):  800-1,400 mg/day
    * Group B:  Peg-Intron : 1.0 mcg/kg/week and Rebetol (ribavirin):  800-1,400 mg/day
    * Group C:  Pegasys:  180 mcg/week and Copegus (ribavirin):  1,000/1,200 mg/day

All the trial participants were treated for 48 weeks with a 24 week follow-up period, which is the standard duration of treatment for people with genotype 1.  It was reported that there were no significant differences in the patient characteristics.

The sustained virological response (SVR) rates given in the press release were as follows:

    * Group A:  40%
    * Group B:  38%
    * Group C:  41%

It was also stated that the overall adverse events, or side effects, reported were similar between the three arms.

The results released were listed as top line results, which means that no further information was available, just the overall SVR rates.  In addition the p-values, or confidence intervals, which would  give us a better idea of whether or not the results are truly statistically significant, were not listed.  However, it was noted that more of the data will be submitted for peer-reviewed publication and for presentations at upcoming medical meetings.  It is expected that Schering will release more information at the upcoming European Association for the Study of Liver Diseases (EASL) that will be held in April 2008.

Bottom line:
The top line results suggest that the effectiveness of Peg-Intron at the lower dose of 1.0 mcg/kg is at least equivalent to the higher dose of 1.5 mcg/kg.

The results comparing Peg-Intron vs. Pegasys have been promoted as a head-to-head study.  However, as I pointed out above, the part of the clinical trial comparing Peg-Intron vs. Pegasys was poorly designed because in truth the dose of ribavirin given to trial participants taking Peg-Intron was different than the ribavirin dose given to the people who were taking Pegasys.  For instance, in the Peg-Intron arms the dose of  Rebetol (ribavirin) was 800 – 1,400 mg/day (weight based), but the dose of Copegus (ribavirin) in the Pegasys arm was 1,000-1,200 mg/day (weight based).  In addition, the dose reduction schedule for Peg-Intron was different than the dose reduction schedule for Pegasys.  This is an important issue because in the last few years we have learned that taking the optimal dose of ribavirin is one of the most important factors in achieving an SVR.  In addition the different ribavirin dose reduction schedule also affects the use of growth factors for the management of ribavirin-related anemia.  Finally, it was pointed out in the Roche press release that the study arm with Pegasys was not blinded so there could be a potential for patient or provider bias.

The FDA is the government body that approves all clinical trial designs for clinical trials that take place in the United States.  Clearly someone at the FDA was asleep at the wheel when they approved the third arm of this study.  In the future it is hoped that the FDA will take a more proactive role in determining and approving appropriate studies that will give providers and patients more clinically significant information.

Ето и какво мисли Roche за изследването на Schering:
Roche Stands By Their HCV Drugs Citing "IDEAL" Study Design Issues

Roche Stands By Their HCV Drugs Citing "IDEAL" Study Design Issues

Indicating patient preference for PegIntron™, Schering-Plough recently publicized their Hepatitis C trial, "IDEAL." However, competitor Roche indicates several IDEAL trial design issues that make for a poor comparison to their PEGASYS® with COPEGUS®.

Media Release

Contacts:
Brad Jenkins, Roche
+41 61 68 86404

Michelle Marchione
Axon Communications
+1 416 848 1419

Roche responds to announcement of “IDEAL” hepatitis C study

BASEL – January 14, 2008 – Following an announcement from Schering-Plough, Roche today affirmed the value of PEGASYS® (peginterferon alfa-2a) in combination with COPEGUS® (Roche’s brand of ribavirin) as the market-leading treatment for patients with hepatitis C. Despite clear biases in the design of the “IDEAL” study that potentially favoured patients taking PegIntron™ (peginterferon alfa-2b) regimens – particularly the ribavirin dose reduction protocol – the study results have shown that patients treated with a PEGASYS regimen had a similar chance of being successfully treated for hepatitis C.

“I do not expect that the results of the IDEAL study will meaningfully impact clinical practice, except to inform physicians on the appropriate dosing of PegIntron and to reinforce the already widely-accepted view that optimising ribavirin dosing throughout treatment is critical to achieving success and preventing treatment relapse in hepatitis C,” said Douglas Dieterich, M.D., Professor of Medicine in the Division of Hepatology at Mt. Sinai School of Medicine in New York, New York.

In 2001, the U.S. Food and Drug Administration (FDA) required Schering-Plough to conduct a post-approval commitment trial to determine if a lower dose of PegIntron (1.0 mcg/kg) was as effective as the approved dose of 1.5 mcg/kg, both in combination with identical ribavirin regimens.1 A third arm was added to the study in which patients received PEGASYS 180 mcg with a different ribavirin dosing schedule. This mismatch of ribavirin dosing introduces several potential biases into the study because experts agree that an optimised dose of ribavirin, with either pegylated interferon, is critical to achieving success in hepatitis C treatment. In particular, maintaining a full dose of ribavirin has shown an important ability to reduce relapse following the end of treatment.

“PEGASYS quickly became the market leader after its launch, based on robust clinical data and patient and physician preference. We are convinced that physicians and patients will continue to choose the PEGASYS plus COPEGUS combination therapy based on positive experience and sound clinical evidence,” said Rob Mitchell, Head of Viral Diseases Strategic Marketing at Roche. “Our current focus at Roche is on advancing the treatment of hepatitis C by optimising doses and duration of PEGASYS and ribavirin in patients with unmet medical need, while developing new compounds that have the potential to offer a successful outcome to even more patients.”

Roche believes that it is critical for patients and physicians to receive complete information to fully understand the results of “IDEAL” so that treatment decisions can be based on scientific data.
###

Please see below for additional information about the “IDEAL” trial, Roche and PEGASYS including important safety information.

“IDEAL” Trial Design Issues
· Starting doses of ribavirin were different in the PegIntron and PEGASYS arms of the study
· The design calls for a more drastic ribavirin dose reduction for side effect management in most patients in the PEGASYS arm compared to patients in the PegIntron arms; in some cases, ribavirin dose reductions for patients in the PEGASYS arm were three times greater than for patients in the PegIntron arms. This is important because a substantial number of patients being treated for hepatitis C require their ribavirin dose to be reduced to manage side effects, and this could have an impact on the efficacy of the regimen
· The PEGASYS arm was not blinded, meaning that patients and physicians knew which treatment was being administered. Many comparative studies are blinded to ensure that bias does not compromise the results
· Erythropoetin (EPO) is a medication that is often given to treat ribavirin-related anemia and help patients maintain a higher ribavirin dose. However, physicians could only prescribe EPO after the first dose ribavirin reduction in the “IDEAL” trial. Since patients in the PegIntron arms generally had smaller ribavirin dose reductions, this introduces another potential bias and means those PegIntron patients were potentially able to maintain a higher dose of ribavirin compared to PEGASYS patients

Efficacy of PEGASYS plus COPEGUS Combination Therapy
PEGASYS was launched by Roche in 2002 and quickly became the leading treatment for patients with hepatitis C. PEGASYS plus COPEGUS is the only pegylated interferon combination regimen to have demonstrated significantly superior benefits over conventional interferon combination therapy across all HCV genotypes, irrespective of viral load.2-4 The combination of PEGASYS and COPEGUS consistently shows high cure rates – up to 66% overall sustained virological response – across a number of large, randomised clinical studies including in patients with difficult-to-cure disease such as genotype 1 HCV, cirrhosis, and HIV-HCV co-infection.2-7

About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world’s biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is the world leader in diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolism and central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche employs roughly 75,000 worldwide and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai.

###

All trademarks used or mentioned in this release are protected by law.

References:

1. FDA letter to Schering-Plough, August 7, 2001. Accessed Nov. 26, 2007 at: http://www.fda.gov/cder/foi/appletter/2001/pegsche080701L.htm
2. Swan, T. Expediency, Cost-Cutting, Expediency Trump Science in Clinical Development Plan for Peg-Intron: The head-to-head that wasn’t. TAGLine 2003: 10(10)1-4. Also available at: http://www.aidsinfonyc.org/tag/taglines/0312.pdf
3. Raymond, D. The Real IDEAL: Peg-Intron vs. Pegasys. Hepatitis C Harm Reduction Project Web site. Accessed Dec. 17, 2007 at: http://hepcproject.typepad.com/hep_c_project/2004/05/the_real_ideal_.html
4. Hadziyannis SJ, Sette H, Jr., Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004;140(5):346-55.
5. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004;351(5):438-50.
6. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347(13):975-82.
7. Marcellin P, Brillanti S, Cheinquer H. Peginterferon alfa-2a (40KD) (PEGASYS) plus ribavirin (COPEGUS) is an efficacious and safe treatment for chronic hepatitis C (CHC) in patients with compensated cirrhosis. . In: 38th Annual Meeting of the European Association for the Study of the Liver (EASL) July 3-6; 2003; Geneva, Switzerland; 2003.

Поздрави,
Радо

[nevron]

Да, на испанските линкове става въпрос за същото изследване "ИДЕАЛ"!

П.П. Аз си помислих, че имаш някаква компютърна програма за превод от чужди езици, за това и постнах директно линковете. Няма ирония, човече!
Поздрави!

[Stefan]

здрасти Митко,

радвам се че си стигнал до последната права до започване на лечението. като им пратиш документите отнема до около две седмици да ти дадат отговор. на мене докотора ми каза че предпочитал пегасис защото с другите трябвало да следи теглото и съответно да се променя дозата. това му беше единствения аргумент. сигурно диспута е доста по сложен и аз не бих ти препорачал нищо зашото незнам кое би било по добро. взимай квото ти дадат без пари и това е
страничните ефекти сигурно и при двата са едни и същи, защото лекарството действа по един и същи начин на организма

поздрави

[mitko chi]

Здравейте всички,
В събота получих документите от Roche за кандидатсване за безплатни лекарства, а днес ми се обадиха от болницата, за да ми кажат, че резултатите от новите тестове са ми готови. Общо взето са нормални, само cryroglobulina ми е малко висок.
В момента HCV-RNA ми е 860 000 UI/mL, август месец в България ми беше 4 600 000, т.е. сега ми е доста по-нисък.
Не знам тази разлика дали не е грешка, или просто е така.
В четвъртък ще нося молбата на доктора - да я попълни и след това я пращам на Roche. Не знам колко време е нужно за цялата тази процедура. Надявам се до април, май, ако всичко е наред да започна лечение, което би трябвало да е 11 мес.
      Чао засега. Късмет на всички и УСПЕШНО излекуване!!!!!!

[Силвана Лесидренска]

Късмет! Сигурна съм че всичко ще е наред с теб, така че давай смело