Fulranumab in Knee or Hip Osteoarthritis

I have been quite surprised to read this morning about fulranumab in knee and hip osteoarthritis. Rheumatology Network referred to a study on fulranomab in osteoarthritis pain [1]. Fulranomab is a monoclonal antibody that selectively targets nerve growth factor (NGF). It targets NGF like tanezumab [2], on which we didn’t hear much after the US FDA had imposed a partial clinical hold on studies due to unexpected adverse events. The point had been osteonecrosis [ON], but later this serious adverse event had been “downgraded” to rapid progression osteoarthritis [3]: “Despite initial reports, tanezumab treatment was not associated with an increase in ON but was associated with an increase in RPOA [rapid progression osteoarthritis].”

But let’s come to the study by P. Sanga and colleagues [4]: “Long-Term Safety and Efficacy of Fulranumab in Patients With Moderate-to-Severe Osteoarthritis Pain: A Phase II Randomized, Double-Blind, Placebo-Controlled Extension Study”. The authors concluded: “Long-term treatment with fulranumab was generally well-tolerated and efficacious. RPOA was observed as a safety signal. Future studies are warranted to demonstrate whether the risk of RPOA can be reduced in patients taking fulranumab.” We talk about a phase II double-blind, placebo-controlled extension study of 401 patients. “Overall, 81 joint replacements were performed in 71 patients (8 [11%] receiving placebo and 63 [89%] receiving fulranumab); 15 patients (21%) had rapid progression of OA (RPOA).” I don’t read this as “long-term treatment with fulranumab was generally well-tolerated and efficacious.” I read the results as if you receive fulranumab you have a higher chance for joint replacement. Maybe one of the authors could clarify this discrepancy.

I have a problem with MABs like tanezumab, fasinumab or fulranumab in osteoarthritis as pain and not reversing the course of osteoarthritis is addressed.

Adisinsight noted as most recent event: “24 Jun 2016 Takeda terminates its licence for fulranumab in Japan” (25 Mar 2017) [5].

John Carroll had written an article last year: “That blockbuster anti-NGF pain drug fulranumab? J&J doesn't want it anymore” [6]. Last year J&J had decided to hand back fulranumab to Amgen. The reason given: “This decision was based on strategic portfolio prioritization and was not based on any emerging safety concerns from the Phase 3 clinical studies with fulranumab”. I can understand this very well.

If we look at fulranumab, we should also look at tanezumab and fasinumab. A metaanalysis for tanezumab has been punblished by Shun-Li Kan and colleagues last year [7]. Conclusion: “Tanezumab can alleviate pain and improve function for patients with OA of the knee. However, considering the limited number of studies, this conclusion should be interpreted cautiously and more clinical randomized controlled trials are needed to verify the efficacy and safety of tanezumab for OA of the knee.” Last year “the FDA (U.S. Food and Drug Administration) had placed the Phase 2 study for fasinumab for the indication of osteoarthritis pain and chronic back pain on clinical hold” [8].

One unmet need for the treatment of osteoarthritis is a safe and effective pain medication. I don’t see this need being met by anti-NGF-MABs like furanumab, tanezumab or fasinumab. Moreover these drugs do not seem to lead to a better course of osteoarthritis degenerating joints.

Links:

[1] http://www.rheumatologynetwork.com/osteoarthritis/anti-ngf-fulranumab-effective-pain-control-osteoarthritis?GUID=71CAAEF6-94A2-4616-B379-17C18CF13750&rememberme=1&ts=16052017

[2] http://rheumatologe.blogspot.de/2015/12/tanezumab-in-osteoarthritis-at-acr-2015.html

[3] https://www.ncbi.nlm.nih.gov/pubmed/26554876

[4] http://onlinelibrary.wiley.com/doi/10.1002/art.39943/abstract

[5] http://adisinsight.springer.com/drugs/800024342

[6] http://www.fiercebiotech.com/biotech/blockbuster-anti-ngf-pain-drug-fulranumab-j-j-doesn-t-want-it-anymore

[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905652/

[8] http://marketrealist.com/2016/11/teva-pharmaceutical-regeneron-continue-develop-ngf-antibody-fasinumab-2016/

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Methotrexate in Knee Osteoarthritis Revisited

There had been an article on methotrexate (MTX) in knee osteoarthritis (OA), which had been published in 2014. As it had been a double-blind, randomized controlled trial, I had had a closer look at the article back then (1). Abou-Raya and colleagues submitted and published: "Methotrexate in the treatment of symptomatic knee osteoarthritis: randomised placebo-controlled trial". I had been critical about the article and the results of the study. Today I revisited the article, as I wanted to know more on subsequent trials.

I was quite surprised that the article had been retracted. The Annals of Rheumatic diseases discussed the decision (2). They listed eight points of “great concern”. And the Investigation Committee’s report concluded: “There is an unintentional mistake in the statistical process, with errors in collection of data in some groups”.

Let’s hope that Sarah R. Kingsbury and colleagues fare better with their study: “Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase III trial of treatment effectiveness (PROMOTE): study protocol for a randomized controlled trial”. (3) Discussion: “The PROMOTE trial is designed to examine whether MTX is an effective analgesic treatment for OA. The MRI substudy will address the relationship between synovitis and symptom change. This will potentially provide a much needed new treatment for knee OA.” The follow-up should have been completed by December 2016, so we should get results during 2017. Allow me already to voice some doubts. MTX is an immunosuppressant and any reduction of pain is due to this mode of action (4). Chronic low-grade inflammation is thought as a major driver of joint degradation in osteoarthritis (5); and it's unclear if MTX suppresses this kind of inflammation. “Despite the clear role of inflammation in OA, recent trials of potent anti-inflammatory therapies, including use of systemic and intra-articular biologic agents to inhibit TNFα and IL-1β, proved disappointing [Hunter, 2008].” 

But let’s wait for the publication of the PROMOTE study, which I’ve just misspelled as PRO MORTE. 

Links:

http://rheumatologe.blogspot.de/2015/05/methotrexate-in-knee-osteoarthritis.html (1)

http://ard.bmj.com/content/early/2016/06/08/annrheumdis-2013-204856 (2)

http://rheumatologe.blogspot.de/2015/05/methotrexate-in-knee-osteoarthritis.html (3)

http://rheumatologe.blogspot.de/2014/01/methotrexate-mode-of-action.html (4)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3638313/ (5)

Fish oil in knee osteoarthritis?

“Fish oil in knee osteoarthritis?” is an interesting question. I’ve already mentioned a study here on this blog:

Fish oil and knee OA

Poster #2147: Fish oil doesn't have an effect on structural progression of knee OA. They used 9 g, which would be 18 cps. in Germany.

29.10.2013

The researchers sit predominantly in the area of Adelaide (University of Adelaide) and I’ve been in contact with them. In different groups they research fish oil in rheumatoid arthritis and other diseases.

Now, they’ve published two year data on Fish oil in knee osteoarthritis (OA). 202 patients with knee OA were randomised 1:1 to high-dose fish oil (4.5 g omega-3 fatty acids) 15 ml/day or low-dose fish oil (blend of fish oil and sunola oil; ratio of 1:9, 0.45 g omega-3 fatty acids) 15 ml/day. “The primary endpoints were Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score at 3, 6, 12 and 24 months, and change in cartilage volume at 24 months. Secondary outcomes included WOMAC function, quality of life, analgesic and non-steroidal anti-inflammatory drug use and bone marrow lesion score.” Results: “…the low-dose fish oil group had greater improvement in WOMAC pain and function scores at 2 years compared with the high-dose group …” Other endpoints didn’t reach statistical significance. The authors concluded: “In people with symptomatic knee OA, there was no additional benefit of a high-dose fish oil compared with low-dose fish oil. The combination comparator oil appeared to have better efficacy in reducing pain at 2 years, suggesting that this requires further investigation.”

Maybe, maybe not. The study didn’t have a placebo arm. Maybe omega-3 fatty acids like in fish, fish oil or flax oil will have a place in the treatment of rheumatoid arthritis or other auto-inflammatory diseases, but knee osteoarthritis might not benefit. However, I don’t want to sound too apodictical – please go on with your research.

References:

http://rheumatologe.blogspot.de/2013/10/acr-meeting-2013-in-san-diego.html

CL Hill et al.: Fish oil in knee osteoarthritis: a randomised clinical trial of low dose versus high dose. Ann Rheum Dis. 2016 Jan;75(1):23-9. doi: 10.1136/annrheumdis-2014-207169. http://www.ncbi.nlm.nih.gov/pubmed/26353789

Hyaluronic Acid Injections at the ACR 2015 Meeting in San Francisco

There have been two publications on hyaluronic acid injections at the ACR 2015 Annual Meeting in San Francisco.

Kevin Ong and colleagues analyzed retrospective data: “Hyaluronic Acid Injections in Knee Osteoarthritis Patients Are Associated with Delay to Knee Arthroplasty”. They concluded: “Our analysis of elderly knee OA patients showed a significantly longer delay to KA [knee arthroplasty] for those who were treated with HA [hyaluronic acid].” The authors presented a retrospective, observational study, which cannot take into account the placebo effect of an injection. It lacks a control group. Or do we have a control group?

Astrid in “Fringe” asked Dr. Walter Bishop: “What’s this?” And Walter answered: “A watermelon as a control group.”

I don’t see the two groups comparable; the second group isn't a control group. The time intervals are differently fixed: one with the treatment and the other one arbitrarily.

There may be other reasons as well: different coping attitudes (one trying to avoid arthropasty and the other wishing an arthroplasty), waiting for therapeutic effect or others.

All in all, I don’t think that this study has a good point to convince us of using hyaluronic acid in delaying the time to knee arthroplasty.

Gurjit S. Kaeley and colleagues also used retrospective data in their study: “Utilization of Viscosupplementation: 2011 – 2013”. The authors wanted to estimate and compare the prevalence and cost of Viscosupplemention utilization as recent “ American Academy of Orthopedic Surgeons (AAOS) guidelines have strongly recommended against use of hyaluronic acid because of lack of clinical improvement compared with placebo.” The authors concluded: “This study highlights the significant cost of VS [viscosupplementation ] in the Medicare population. […] In view of the negative recommendations by the AAOS [American Academy of Orthopedic Surgeons] against the use of Hyaluronic acid joint injections, the current trajectory of use of Hyaluronic acid may not represent optimal value care.”

Hyaluronic acid in knee osteoarthritis hasn’t proven efficacy like clinical improvement compared with placebo or delaying the time to knee arthroplasty. Therefore guidelines recommend against using it.

In Germany hyaluronic acid injections aren’t covered by the compulsory health insurance system, so patients have to pay for injection and medication.

I would not use hyaluronic acid in knee osteoarthritis.

References:

Ong K, Anderson A, Lau E, Niazi F, Fierlinger A, Kurtz S, Altman R. Hyaluronic Acid Injections in Knee Osteoarthritis Patients Are Associated with Delay to Knee Arthroplasty [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/hyaluronic-acid-injections-in-knee-osteoarthritis-patients-are-associated-with-delay-to-knee-arthroplasty/. Accessed November 16, 2015.

Kaeley GS, Thway M, Dodani S. Utilization of Viscosupplementation: 2011 – 2013 [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/utilization-of-viscosupplementation-2011-2013/. Accessed November 16, 2015.

Methotrexate in Knee Osteoarthritis

I've been pondering about an article on methotrexate (MTX) in knee osteoarthritis (OA), which had been published in 2014. As it had been a double-blind, randomized controlled trial. It’s well worth to have a look at it. The article had been published in the Annals of Rheumatic Diseases (Ann Rheum Dis doi:10.1136/annrheumdis-2013-204856).

A. Abou-Raya and colleagues:

"Methotrexate in the treatment of symptomatic knee osteoarthritis: randomised placebo-controlled trial". Methods: "One hundred and forty-four patients with primary knee OA were randomised in a 1:1 ratio to receive up to 25 mg/week oral MTX (n=72) or placebo (n=72) for 28 weeks." Conclusions: "MTX significantly reduced pain and improved synovitis. There was a significant improvement in physical function. MTX may be a therapeutic option in the treatment of pain and inflammation related to knee OA."

If you closely at the methods in the abstract, you don't see the flaw (maybe it isn't a flaw - we'll look closer into it later). The objectives, however, already give us a hint: "To assess the efficacy of methotrexate (MTX) in decreasing pain and inflammation in symptomatic knee osteoarthritis (OA)." If you look it up in the whole text, you see, that randomization took place after an entrance exam and patients were not consecutive in the manner of reflecting patients with "symptomatic knee osteoarthritis", instead we're looking at a subset of patients, most of whom were overweight women in their mid-60s with advanced knee OA and clinical evidence of synovitis. The text doesn't explain if any are suffering from concomitant rheumatoid arthritis.

What does the study really say? There might be a subset of knee OA patients, who might benefit from MTX. Then why not say so clearly? The headline doesn’t tell exactly, what the study is about. I think, we're far from using MTX in knee OA patients in daily practice; but as were lacking drugs to alter the course of osteoarthritis, some more scientific effort is warranted. If MTX turns out to be a drug for even only a subset of knee OA patients, we're indebted to A. Abou-Raya and colleagues.

Hyaluronic acid injection for Knee Osteoarthritis

Rheumatology News has an article on a study telling us “Hyaluronic acid injection for knee OA as effective as NSAIDs in short term” (Links are listed below).

The study is from Japan. It’s a multicenter, randomized, open-label, parallel-group, non-inferiority comparison study. One group received a weekly injection injection into the (one?) knee for five weeks and the other group received three times 60 mg of loxoprofen, which is an NSAID of the same group like ketoprofen or ibuprofen. Loxoprofen is only available in Japan, Mexico, Brazil, Argentina, and India. The primary endpoint was the percentage change in the patient-oriented outcome measure for knee OA, the Japanese Knee Osteoarthritis Measure (JKOM) score. Rheumatology News tells about the secondary endpoint: “and their percent change from baseline in pain as rated on a 0- to 100-point visual analog scale (VAS, secondary endpoint).”

Results: "The difference in the percentage changes of the JKOM score between the two intervention arms (IA-HA; - 34.7 % (P < 0.001), NSAID; - 32.2 % (P < 0.001)) was - 2.5 % (95 % confidence interval (CI): - 14.0 to 9.1), indicating IA-HA was not inferior to NSAID. The frequency of both withdrawal and adverse events in the IA-HA group were significantly lower than those in the NSAID group (P < 0.026 and 0.004, respectively)."

The study tells us, that after five weeks of treatment the effects of hyaluronic acid injection for knee OA is equal to an NSAID. How about the first two weeks? Is hyaluronic acid working or the injection itself? Invasive manipulations have a high percentage of placebo effect, but we do not have a placebo control group. We don’t even know if the control group is disappointed not getting their injections and therefore have less pain relief. Withdrawal in the NSAID group had been higher, but the use of gastro protective agents has only been allowed and not been mandatory.

The study has been perfectly done, but it fails to prove that hyaluronic acid injection for knee OA is the road to follow.

Links:

Article on Rheumatology News - http://www.rheumatologynews.com/index.php?id=8844&tx_ttnews[tt_news]=235121&cHash=04c039bf543c2984f1ad4aa5f1b6af91&utm_medium=twitter&utm_source=twitterfeed

Abstract of the study - http://arthritis-research.com/content/16/1/R18/abstract

Loxoprofen on Wikipedia - http://en.wikipedia.org/wiki/Loxoprofen

ARRY-797 at the ACR2012 in Washington

There has been a late breaking abstract on ARRY-797 about ... osteoarthritis. ARRY-371797 is a p38 inhibitor. There have been some studies on the way:
• A Study of ARRY-371797 in Patients With Rheumatoid Arthritis
• A Study of ARRY-371797 in Patients With Active Ankylosing Spondylitis
These studies had been completed by July 2012, but nothing has been published at the EULAR 2012 meeting in Berlin or at the ACR 2012 meeting in Washington. And then a late breaking poster on osteoarthritis. What does it mean? My guess is that p38 inhibition isn’t working in RA and AS, but the producer (Array BioPharma) is looking desperately for an indication to put the drug on the market. OK, let’s have a closer look, if ARRS-797 is a candidate to treat osteoarthritis.

Alan J. Kivitz and colleagues presented the following study [Abstract No. L1]: “A Randomized, Placebo-Controlled Phase 2 Study of ARRY-797 in Patients with Osteoarthritis Pain Refractory to NSAID Treatment Showed Statistically Significant Improvements in WOMAC Pain and in Biomarkers of Bone and Cartilage Degradation.” Conclusion: “ARRY-797 treatment resulted in durable, statistically significant improvement in OA pain and in reduction of circulating biomarkers of both cartilage and bone degradation in this 4-week study. Further evaluation of the efficacy of this non-opioid analgesic and the potential for disease modifying activity are warranted.”

Wait a Minute! Let’s have a closer look at the results of the WOMAC Pain Score!

Change from Baseline in WOMAC Pain (0-10 NRS)
Study Visit    ARRY-797    Placebo    Oxy ER
Week 1            1.6*             0.9           2.0*
Week 2            1.7              1.3           2.0*
Week 3            2.1              1.7           2.0
Week 4            2.4*             1.6           1.9
BOCF/LOCF. * p _0.05 (2-sided) versus Placebo

“Durable improvement” – ARRY-797 is significantly better than placebo only at week 1 and week 4. The pain reduction of ARRY-797 at week one is equal to placebo at week 4. At best ARRY-797 reduces the pain better than placebo by 0.8 on the NRS. Let’s put the initial pain score at 8.5, placebo would reduce this to 6.9 and ARRY-797 to 6.1. Big deal! Even the much criticized study of L.A. Crofford on pregabalin in fibromyalgia worked with a pain reduction of at least 50% against baseline. ARRY-797 is very far from this goal.

The authors also listed some adverse events in patients treated with ARRY-797: “mild to moderate skin-related disorders, dizziness, diarrhea and stomatitis. Transient increases in CK and mild prolongations in the QTc interval were also noted.”

Well, I don’t think ARRY-797 is a good candidate for a drug on treating osteoarthritis. ARRY-797 hasn’t yet shown so much efficacy to warrant already noticed risks and expected costs.

19.06.2013
Nothing new on ARRY-797 at the EULAR Meeting 2013 in Madrid. But according to the homepage of Array Biophama the project isn't abandoned. Not working in RA and AS, and only mild effects in OA. It seems strange that the company ran for a late breaking poster and doesn't publish more now. I don't see ARRY-797 on the market.

ARRY-797 at the ACR2012 in Washington

There has been a late breaking abstract on ... osteoarthritis.

ARRY-371797 / ARRY-797 is a p38 inhibitor (P38 mitogen-activated protein kinases [MAPK]). There were some studies on the way:
• A Study of ARRY-371797 in Patients With Rheumatoid Arthritis
• A Study of ARRY-371797 in Patients With Active Ankylosing Spondylitis
• A Study of ARRY-371797 in Patients With Osteoarthritis of the Knee

All three studies have been completed by July 2012, but nothing has been published at the EULAR 2012 meeting in Berlin and I haven’t seen any results the ACR 2012 in Washington. What does it mean? My guess is that p38 inhibition isn’t working in RA and AS, but the producer (Array BioPharma) is looking desperately for an indication to launch the drug on the market.
Alan J. Kivitz and colleagues presented a study (Abstract No. L1): “A Randomized, Placebo-Controlled Phase 2 Study of ARRY-797 in Patients with Osteoarthritis Pain Refractory to NSAID Treatment Showed Statistically Significant Improvements in WOMAC Pain and in Biomarkers of Bone and Cartilage Degradation”. Conclusion: “ARRY-797 treatment resulted in durable, statistically significant improvement in OA pain and in reduction of circulating biomarkers of both cartilage and bone degradation in this 4-week study.” That’s quickly said! ARRY-797 only showed a significant WOMAC pain reduction at weeks 1 and 4 at p>/= 0.05

Is this a meaningful reduction of pain? My guess is it isn’t, otherwise one would have said so.
Please have a look at my more elaborate evaluation under: 

http://rheumatologe.blogspot.de/2013/02/arry-797-at-acr2012-in-washington.html

A Diet for Osteoarthritis?

Sorry, there isn’t a diet for osteoarthritis (OA), but there are useful dietary measures you can take to improve on OA. These are long term options. There don’t work fast, but may help to cope with pain, inflammation, and disability. Dietary changes will act prophylactically.

Overweight
Overweight means more to carry. If you loose weight, your pain might also be alleviated. Overweight is a risk factor to develop OA. Once the process is on its way, loosing weight might not stop the changes in the joints, but still help in pain and severity.

Cherries, anthocyanins, and inflammation
I had been looking for cherries and gout attacks recently and found a study on inhibition of IL-6 and anthocyanins of cherry tart: http://www.ncbi.nlm.nih.gov/pubmed/22703874. And others have been tested as well: black raspberries, strawberries, sweet potatoes, … Most probably all foods that have an effect on free radicals like anthocyanin, flavonoids, carotenoids, and more will also have an effect on inflammation. Cherries don’t contain as much anthocyanins like blackberries, elderberries, blueberries, or black currants.

Carotenoids, vitamin E and C
Carotenoids, vitamin E and C might be helpful in OA. There is an old study: http://www.ncbi.nlm.nih.gov/pubmed/8630116. These results reflect the amount of these compounds as takes in the diet, not to take supplementation products. If the diet is rich in carotenoids, vitamin E and C, you have a diet with lots of fresh vegetables, fruits, and nuts. You may at the same time reduce some harmful substances.

Iron
Too much iron will increase inflammation. We need enough iron, for sure, but excess of iron might promote inflammation and OA.

Phytochemicals
Phytochemicals like flavonoids and other polyphenols, like diallyl disulphide in garlic, sulforaphanes in broccoli and other cruciferous vegetables, lycopene in tomatoes might also help.

To sum it up, a more plant-based diet, which contains lots of whole grains, fruits, and veggies (not necessarily a vegetarian diet – that’s an ethic step) might help to avoid the development of osteoarthritis. It also means reducing meats and dairy products will be beneficial.

Strontium ranelate in Knee Osteoarthritis at the EULAR 2012

Strontium ranelate in knee osteoarthritis has also been advocated at the EULAR 2012 in Berlin. It has been the Cooper/ Reginster study that had been discussed at the IOF-ECCEO12 Congress at Bordeaux earlier this year (http://www.ncbi.nlm.nih.gov/pubmed/22148897). In April this year I've received a Red Hand Letter concerning strontium ranelate (Link to the German text: http://www.bfarm.de/DE/Pharmakovigilanz/risikoinfo/2012/rhb-protelos.html). EMEA and the German Bundesinstitut für Arzneimittel und Medizinprodukte had Servier to inform all physicians in Germany about new risks concerning strontium ranelate. There is a contraindication for patients with acute venous thrombembolism, phlebothrombosis, or pulmonary embolism. Also immobilized patients aren't allowed to take strontium ranelate. Reason for this information is a study that has been published in France. More about risks at: http://www.netdoctor.co.uk/seniors-health/medicines/protelos.html.

C. Cooper and colleagues looked at efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis. The text on “objectives” doesn’t give a clue to an endpoint of the study. In “results” we are given characteristics in mean values of the patients that were assigned to the study in 113 centres. No result whatsoever! In “conclusions” we are given wishful thinking instead of conclusions drawn from results.

[AB0962] EFFICACY AND SAFETY OF STRONTIUM RANELATE IN THE TREATMENT OF KNEE OSTEOARTHRITIS: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED INTERNATIONAL TRIAL
C. Cooper1, R. Chapurlat2, C. Christiansen3, H. Genant4, N. Bellamy5, W. Bensen6, F. Navarro7, J. Badurski8, E. Nasonov9, X. Chevalier10, P. Sambrook11, T. Spector12, J.-Y. Reginster13. 1MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton, United Kingdom; 2INSERM UMR 1033 and Université de Lyon, Hôpital Edouard Herriot, Lyon, France; 3CCBR Ballerup, Ballerup, Denmark; 4Radiology, Medicine and Orthopaedic Surgery University of California San Francisco, and Synarc, San Francisco, United States; 5University of Queensland, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia; 6McMaster University Hamilton, Ontario, Canada; 7H. Clinico Virgen de la Macarena Servicio de Reumatologia, Sevilla, Spain; 8Centre of Osteoporosis and Osteo– articular Diseases, Bialystock, Poland; 9State Institute of Rheumatology, the Russian Academy of Medical Sciences, Moscow, Russian Federation; 10Hôpital Henri Mondor, Créteil, France; 11Royal North Shore Hospital, St. Leonards NSW, Australia; 12Kings College London, St Thomas' Campus, London, United Kingdom; 13University of Liège, Liège, Belgium
Conclusions: This large randomised placebo-controlled study will establish the long-term efficacyof SrRan on structure and symptoms in patients with knee osteoarthritis.


Strontium ranelate isn’t a goal getter in osteoporosis therapy. It has a very low persistence in patients, link: http://www.ncbi.nlm.nih.gov/pubmed/22541835. I don’t think that strontium ranelate will be a goal getter as a drug against knee osteoarthritis. I think Servier is desperately seeking a new indication to sell strontium ranelate.

Addition at 20. February 2013:
There's an editorial in this month's isssue of the Annals of the Rheumatic Diseases (Ann Rheum Dis 2013;72:157-161 doi:10.1136/annrheumdis-2012-202453) by  Floris PJG Lafeber and Jacob M va Laar: "Strontium ranelate: ready for clinical use as a disease-modifying osteoarthritis drug?" In this editorial they also discussed cindunistat and statins, but had to conclude: "Clearly, none of the three drugs presented is ready for use as a DMOAD [Disease Modyfying Osteoarthritis Drug] in clinical practice." 

Another addendum 10.05.2013:
Strontium ranelate (Protelos®; Osseor®) ist in the discussion at the EMA. 2011 a French study showed 199 severe adverse events, 52% cardiovascular events [4.Jonville-Bera AP, et al: Presse Med. 2011: 40(10): e453-e462. http://dx.doi.org/10.1016/j.lpm.2011.07.010 as cited by Medscape Germany]. 2012 the Committee for Medicinal Products for Human Use (CHMP) added deep vein thrombosis and pulmonary embolism as contraindications. As there are more safety issues, EMA might further restrict the use of strontium ranelate.
Considering this, one would be well advised not to use strontium ranelate off-label, which would be prescribing the drug in osteoarthritis patients.

Arthrose – weitere Aufreger in der orthopädischen Zeitschrift für Patienten

Ich lese gerade in einer Zeitschrift, die unsere Orthopäden für die Patienten im Wartezimmer ausgelegt haben – ein Aufreger nach dem anderen.


„Beweglicher mit Hyaluronsäure-Kapseln“ und mit ähnlichen Versprechen werden Nahrungsergänzungsmittel beworben. Die Versprechen basieren aber nicht auf entsprechenden Studien, da dies auch nur für Medikamente nach dem Arzneimittelgesetz vorgesehen ist. Das Nahrungsergänzungsmittel wird aber wie ein Arzneimittel beworben. Wahrscheinlich wird es weder Wirkung noch Nebenwirkung haben, außer natürlich der Wirkung auf den Geldbeutel des Käufers, denn der wird leerer.


Dann wird ein „individueller Ernährungsplan“ für sage und schreibe 400 € aufgestellt. Wahrscheinlich kauft man sich überflüssige und nicht in Studien verifizierte, also völlig obskure Laborwerte ein, ohne die der „persönliche Fahrplan“ für die Ernährung nicht erstellt werden kann. Damit soll man auch das Gewicht reduzieren können. Vorsichtig sollte man werden, wenn man im Zusammenhang mit Gewichtsreduktion von Pfunden liest, die da purzeln.


Ein Buch zu Knie-Arthrose verspricht Hoffnung für Arthrosepatienten: „Vorbeugung, Behandlung, Heilung“. Heilung? Ja, steht auf dem Buchtitel. In Wikipedia findet man folgenden Definitionsversuch: „In der Medizin wird Heilung als Wiederherstellung des Gesundheitszustandes unter Erreichen des Ausgangszustandes (restitutio ad integrum) definiert.“ Und das ist nun mal nicht möglich. Weiter in Wikipedia: „Bleibt ein organischer oder funktioneller Restschaden bestehen, spricht man von Defektheilung.“ Wahrscheinlich werden sich die Autoren darauf zu berufen wissen.


OT: Nun steht etwas über Rheuma in der Zeitschrift. „Einige der wichtigsten langwirksamen Antirheumatika sind: * intramuskulär verabreichtes Gold bzw. in Tablettenform (z.B. Tauredon® oder Ridaura® ...“ Gold (Tauredon®) ist nur noch als Reservemittel üblich, da die modernen Mittel effektiver sind und weniger unerwünschte Arzneimittelwirkungen haben. Bei Ridaura® war die Wirksamkeit nie bewiesen. Aber die Autorin weiß dies alles nicht.


Eine Magnetfeldfeldtherapie wird als „Kraftwerk gegen die Schmerzen“ eingesetzt. Es ist unwahrscheinlich, dass durch diese Technik eine Besserung erfolgt. Siehe auch: http://www.ncbi.nlm.nih.gov/pubmed/21938735 (englischer Text). Dann wird dreist behauptet:“Gerade bei Osteoporosepatienten kann in der Langzeitbehandlung eine enorme Steigerung der Knochendichte beobachtet werden.“ Da ist die Wissenschaft aber völlig gegenteiliger Ansicht: http://www.ncbi.nlm.nih.gov/pubmed/22249842 (englischer Text). Ich nehme an, dass der Einsatz dieser pulsierten Magnetfeldtherapie eine „enorme Steigerung“der Einkünfte dieses Arztes bewirkt hat.


„Dank dieser berühmten Schweizer Kur nehmen Sie 5 Kilo in 1 Woche ab!“ „... keine Diät, keine ermüdende Gymnastik, keine Willensanstrengung. Sie werden abnehmen – das ist garantiert!“ Das vergessen Sie bitte ganz schnell. Mit gleicher Chuzpe könnte man die Super Goldkörnchen bewerben, die den Geldbetrag auf Ihrem Konto steigern, denn: „Sie werden reich – das ist garantiert!“. Und dann sehe ich noch, dass der Vorrat „schnell zur Neige geht“. Auch eine beliebte Methode, Panikkäufe hervorzurufen.


Dann folgt ein Wundermittel gegen Arthrose: „Ein natürliches Mittel, das Sie in 3 Monaten von Arthroseschmerzen befreit!“ Artro silium heißt das Mittel. Hier ist ein Forum, dass sich damit beschäftigte: http://www.rheuma-online.de/phorum/printthread.php?t=13485 (Vorsicht, da trollen sich auch Befürworter drin, die ziemlich sicher vom Vertreiber ausgehen). Der Hauptbestandteil des überteuerten Gels ist Kieselerde. Das ist auch der Hauptbestandteil von Zahnpasta. Zahnpasta als Mittel gegen Arthrose würde zwar nur ca. ein Zwanzigstel kosten, aber nicht so gut klingen.


Und jetzt habe ich erst einmal genug geblättert.