Featured Research

from universities, journals, and other organizations

Ruxolitinib for myelofibrosis: Indication of considerable added benefit

Date:
August 19, 2014
Source:
Institute for Quality and Efficiency in Health Care
Summary:
In comparison with 'best supportive care', there is an indication that the new drug is better at relieving symptoms, and a hint of longer survival. Myelofibrosis is a rare disease of the bone marrow, in which the bone marrow is replaced by connective tissue. As a consequence of this so-called fibrosis, the bone marrow is no longer able to produce enough blood cells. Sometimes the spleen or the liver takes over some of the blood production. Then these organs enlarge and can cause abdominal discomfort and pain.

Ruxolitinib (trade name: Jakavi) has been approved since August 2012 for the treatment of adults with myelofibrosis. In an early benefit assessment pursuant to the Act on the Reform of the Market for Medicinal Products (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether this new drug offers an added benefit over the appropriate comparator therapy specified by the Federal Joint Committee (G-BA).

Related Articles


According to the results, there is an indication of considerable added benefit in comparison with "best supportive care" (BSC) because ruxolitinib is better at relieving symptoms. Moreover, a hint of an added benefit with regard to survival can be derived from the dossier. Its extent is non-quantifiable, however.

Bone marrow is replaced by connective tissue

Myelofibrosis is a rare disease of the bone marrow, in which the bone marrow is replaced by connective tissue. As a consequence of this so-called fibrosis, the bone marrow is no longer able to produce enough blood cells. Sometimes the spleen or the liver takes over some of the blood production. Then these organs enlarge and can cause abdominal discomfort and pain. The typical symptoms also include feeling of fullness, night sweats and itching. Some patients with myelofibrosis develop leukemia.

Stem cell transplantation is currently the only option to cure myelofibrosis. The drug ruxolitinib aims to relieve the symptoms of myelofibrosis.

G-BA specifies appropriate comparator therapy

Ruxolitinib is an option for patients with so-called primary or secondary myelofibrosis whose spleen is already enlarged (splenomegaly) or who have other disease-related symptoms.

The G-BA specified "best supportive care" (BSC) as appropriate comparator therapy. BSC means a therapy that provides the patient with the best possible, individually optimized, supportive treatment to alleviate symptoms and improve quality of life. This also includes adequate pain therapy.

Relevant study ongoing until 2015

In its assessment, IQWiG could include one randomized controlled trial (RCT) conducted in 89 centres in Australia, Canada and the United States (COMFORT-I). The 309 patients in total were either treated with ruxolitinib plus BSC or with placebo plus BSC.

The first analysis (primary analysis) was conducted in 2010 after all patients had been treated for 24 weeks and half of them for 36 weeks. Then all participants were unblinded and could switch to the ruxolitinib arm of the study. If their spleen volume had increased by more than 25%, they could also switch earlier. A 3-year analysis was conducted in 2013. The study was prolonged to 2015, however, to obtain long-term data.

Overall survival: results not consistently significant

With regard to survival time, the differences between the two treatment groups were not statistically significant in favour of ruxolitinib in all of the four analysis dates. Because of the high proportion of patients who switched treatment, the survival advantage of ruxolitinib is rather underestimated. Overall, IQWiG therefore considers there to be a hint of an added benefit. The extent of this added benefit is unclear, however.

Morbidity: fewer symptoms in ruxolitinib group

A disease-specific questionnaire (MFSAF v2.0) was used to record symptoms in the COMFORT-I study. This instrument comprises myelofibrosis symptoms and aggregates them to one value (total symptom score, [TSS]). In the ruxolitinib + BSC group, considerably more patients than in the placebo + BSC group reported that their symptoms have improved.

Regarding the occurrence of leukemia (leukemic transformation), a typical late complication, there were no differences between the two treatment groups in the study.

For the outcome "morbidity," IQWiG therefore recognizes an indication of an added benefit with the extent "considerable."

No evaluable results on quality of life

The dossier contained no evaluable data on quality of life. Quality of life was recorded in the study using an instrument developed for cancer (EORTC QLQ-C30). However, different proportions of participants in the two treatment groups remained unconsidered in the analysis. As the difference of the missing values was more than 20 percentage points, no reliable conclusions can be derived from the results.

For the same reason, the data on symptoms that were also recorded with EORTC QLQ-C30 are also not evaluable.

Only limited conclusions on side effects possible

Only limited conclusions can be drawn on side effects. This is mainly due to the fact that typical symptoms of myelofibrosis, such as night sweats, were also recorded as "adverse events." This means that it remains unclear whether these were side effects of the drug or symptoms of the underlying condition. Such events that are not clearly attributable allow no informative conclusions on side effects.

Although greater harm from ruxolitinib can also not be ruled out completely, the available data contain no signs of harm of a magnitude that might justify downgrading the added benefit as a whole.

Hence the positive effects with regard to symptom relief (indication) and prolongation of life (hint) remain. Overall, IQWiG therefore regards there to be an indication of considerable added benefit of ruxolitinib in comparison with BSC.

First orphan drug with a turnover of over 50 million euros

Ruxolitinib has the status "orphan drug." According to 35a (1), Sentence 10, Social Code Book V [SGB V]), the medical added benefit is regarded as proven if a drug has been approved, as long as the yearly turnover in the statutory health insurance (SHI) funds does not exceed 50 million euros. In this case, the G-BA only has to determine the extent of added benefit. The G-BA made this decision on ruxolitinib in March 2013.

In 2013, ruxolitinib was the first drug for rare diseases to exceed the 50 million euro threshold. The G-BA therefore requested the drug manufacturer to submit proof of the added benefit of ruxolitinib in comparison with the appropriate comparator therapy in a dossier, and commissioned IQWiG with the assessment.


Story Source:

The above story is based on materials provided by Institute for Quality and Efficiency in Health Care. Note: Materials may be edited for content and length.


Cite This Page:

Institute for Quality and Efficiency in Health Care. "Ruxolitinib for myelofibrosis: Indication of considerable added benefit." ScienceDaily. ScienceDaily, 19 August 2014. <www.sciencedaily.com/releases/2014/08/140819125952.htm>.
Institute for Quality and Efficiency in Health Care. (2014, August 19). Ruxolitinib for myelofibrosis: Indication of considerable added benefit. ScienceDaily. Retrieved October 30, 2014 from www.sciencedaily.com/releases/2014/08/140819125952.htm
Institute for Quality and Efficiency in Health Care. "Ruxolitinib for myelofibrosis: Indication of considerable added benefit." ScienceDaily. www.sciencedaily.com/releases/2014/08/140819125952.htm (accessed October 30, 2014).

Share This



More Health & Medicine News

Thursday, October 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Mind-Controlled Prosthetic Arm Restores Amputee Dexterity

Mind-Controlled Prosthetic Arm Restores Amputee Dexterity

Reuters - Innovations Video Online (Oct. 29, 2014) A Swedish amputee who became the first person to ever receive a brain controlled prosthetic arm is able to manipulate and handle delicate objects with an unprecedented level of dexterity. The device is connected directly to his bone, nerves and muscles, giving him the ability to control it with his thoughts. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Google To Use Nanoparticles, Wearables To Detect Disease

Google To Use Nanoparticles, Wearables To Detect Disease

Newsy (Oct. 29, 2014) Google X wants to improve modern medicine with nanoparticles and a wearable device. It's all an attempt to tackle disease detection and prevention. Video provided by Newsy
Powered by NewsLook.com
Can Drinking Milk Lead To Early Death?

Can Drinking Milk Lead To Early Death?

Newsy (Oct. 29, 2014) Researchers in Sweden released a study showing heavy milk drinkers face an increased mortality risk from a variety of causes. Video provided by Newsy
Powered by NewsLook.com
Obama: The US Will Not 'run and Hide' From Ebola

Obama: The US Will Not 'run and Hide' From Ebola

AP (Oct. 29, 2014) Surrounded by health care workers in the White House East Room, President Barack Obama said the U.S. will likely see additional Ebola cases in the weeks ahead. But he said the nation can't seal itself off in the fight against the disease. (Oct. 29) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



    Save/Print:
    Share:

    Free Subscriptions


    Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Get Social & Mobile


    Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

    Have Feedback?


    Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
    Mobile: iPhone Android Web
    Follow: Facebook Twitter Google+
    Subscribe: RSS Feeds Email Newsletters
    Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins