Can we predict who’s going to get arthritis?

Two studies have recently been published that may help us better predict who is at risk for developing arthritis.

The first study, published in the August 2009 edition of Arthritis & Rheumatism  involved an analysis of 912 healthy individuals, including 60 who had severe osteoarthritis that led to knee or hip replacement between 1990 and 2005.  Those study volunteers who had high levels of vascular cell adhesion molecule 1 (VCAM-1) at the start of the study were most likely to require a joint replacement.  VCAM-1 is expressed in cartilage and other connective tissue.  Lead author Georg Schett from the University of Erlangen-Nuremburg in Germany stated, “The level of VACAm-1 emerged as a significant predictor of the risk of joint replacement due to severe OA, equaling or even surpassing the effects of age.”

This study was the first to establish a laboratory biomarker for the risk of severe osteoarthritis.

Biomarkers are tissue markers that have predictive value either as an indicator of likelihood of disease or even a predictor of likelihood of response to a given therapy.

Another study, appearing in the February 2010 issue of Arthritis & Rheumatism,  was one where researchers in Sweden analyzed the blood samples of 342 people, 86 of whom went on to develop rheumatoid arthritis up to five years after giving blood. Overall, the people who ultimately developed rheumatoid arthritis had higher levels of cytokines (immune-related protein messengers) and other substances involved in inflammation in their blood compared to those who didn’t develop the disease.

“Our findings present an opportunity for better predicting the risk of developing RA and possibly preventing disease progression,” concluded Dr. Rantapää-Dahlqvist, one of the authors.

The nice thing about both studies is the possible predictive value.  Knowing ahead of time who is at risk can certainly help clinicians keep a closer eye on symptoms.

Blood biomarkers, in general, though, have weak predictive value when it comes to treatment. What is lacking is a good library of tissue biomarkers (biomarkers from joint tissue) which can help predict what therapy a patient will best respond to.

We are currently involved in a number of studies at our center to identify those tissue  biomarkers in patients with  various forms of arthritis.

If you have rheumatoid arthritis or osteoarthritis, please contact us to see if you might be eligible for one of these studies.  You can call us at 301 694 5800 or email us at aocmd@aocm.org.

Or just leave a message here.

I’m an osteoarthritis junky.  Whatever I can find that might work, I look at.  Many patients have told me that take SAM-e.

All I’ve been able to find is anecdotal reports.

The Cochrane Report recently came out with their analysis of the existing data.  The Cochrane report is really the final word.  They do an exhaustive analysis of everything and their conclusions are usually excellent.  They looked at SAM-e and this is what they found…

OBJECTIVES: We set out to compare S-Adenosylmethionine (SAMe) with placebo or no specific intervention in terms of effects on pain and function and safety outcomes in patients with knee or hip osteoarthritis.

SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE, CINAHL and PEDro up to 5 August 2008, checked conference proceedings and reference lists, and contacted authors.

SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared SAMe at any dosage and in any formulation with placebo or no intervention in patients with osteoarthritis of the knee or hip.

DATA COLLECTION AND ANALYSIS: Two independent authors extracted data using standardised forms. We contacted investigators to obtain missing outcome information. We calculated standardised mean differences (SMDs) for pain and function, and relative risks for safety outcomes. We combined trials using inverse-variance random-effects meta-analysis.

MAIN RESULTS: Four trials including 656 patients were included in the systematic review, all compared SAMe with placebo. The methodological quality and the quality of reporting were poor. For pain, the analysis indicated a small SMD of -0.17 (95% CI -0.34 to 0.01), corresponding to a difference in pain scores between SAMe and placebo of 0.4 cm on a 10 cm VAS, with no between trial heterogeneity (I(2) = 0). For function, the analysis suggested a SMD of 0.02 (95% CI -0.68 to 0.71) with a moderate degree of between-trial heterogeneity (I2 = 54%). The meta-analyses of the number of patients experiencing any adverse event, and withdrawals or drop-outs due to adverse events, resulted in relative risks of 1.27 (95% CI 0.94 to 1.71) and 0.94 (95% CI 0.48 to 1.86), respectively, but confidence intervals were wide and tests for overall effect were not significant. No trial provided information concerning the occurrence of serious adverse events.

AUTHORS’ CONCLUSIONS: The current systematic review is inconclusive, hampered by the inclusion of mainly small trials of questionable quality. The effects of SAMe on both pain and function may be potentially clinically relevant and, although effects are expected to be small, deserve further clinical evaluation in adequately sized randomised, parallel-group trials in patients with knee or hip osteoarthritis. Meanwhile, routine use of SAMe should not be advised.

To see the whole post, go to the Medscape post…

http://www.medscape.com/medline/abstract/19821403?cid=med&src=nlbest

My mother-in-law forwarded this article to me.  Up until recently, ankle replacements have not been very good.  Looks like things are changing.
HEALTH | January 18, 2010
Well: Ankles Gain as Candidates for Joint Replacement
By TARA PARKER-POPE
As baby boomers enter their 60s and 70s, demand for surgery to replace ankles with artificial joints is expected to grow. (http://well.blogs.nytimes.com/2010/01/18/ankles-gain-as-candidates-for-joint-replacement/?emc=eta1)

(I’m also wondering whether this might also be a place where stem cell therapies might also be an option.)

My thanks to Marcia Hearst and hope all is well with her.  She’s a great mother-in-law.

A recent study

[de Vos RJ, Weir A, van Schie HTM, et al. Platelet-Rich Plasma Injection for Chronic Achilles Tendinopathy: A Randomized Controlled Trial. JAMA. 2010;303(2):144-149]

cast a negative light on the use of platelet-rich plasma (PRP) for chronic Achilles tendonitis.

Dutch researchers randomly assigned 54 patients suffering from Achilles tendinopathy to receive either platelet-rich plasma injections or a placebo shot of saline.

Both groups also did conventional rehabilitation consisting of 180 heel drops (an exercise in which the toes are placed on the edge of a step and the heels are lowered toward the step below) daily for 12 weeks.

Results showed no difference between the two groups at six, 12 or 24 weeks after the procedure. Both groups improved about 20 points on a standardized scale that measures pain and function.

Robert-Jan de Vos, MD, in the Department of Orthopedics at Erasmus Medical Center, the lead author, says researchers don’t know why the injections didn’t work and they’re very disappointed by the results.

“These tendon injuries are very hard to treat,” Dr. De Vos said in an article reported in Arthritis Today.  He continued,  “We know that less than 50 percent of the patients with chronic Achilles tendinopathy are free of symptoms after one year. We still cannot prescribe a very promising conservative treatment, which is frustrating for the patients and treating doctors.”

Author’s note:

Many people will point to this study and say that PRP doesn’t work.  My take on it is this.  I think it was a well designed study. Really.  However, there are many explanations for the outcomes reported.

First, the technique used by the person performing the procedure was described as placing three holes in the tendon.  Those of us who do a significant number of Achilles tendon cases know that using a single entry point only and putting that single entry point on the top of the Achilles at an acute angle going from proximal to distal is critical.  Otherwise, the PRP leaks out and the patient won’t have as good a result.

Second any time a tendon is poked with holes without any other type of treatment given, it will improve.  The injury itself sets up an inflammatory response which leads to more healing.

The platelet concentration used was not mentioned.  Some PRP machines only provide a concentration of 2-3 times normal.  That’s not enough.  A good concentrate contains 7-10 times baseline counts of platelets.

No mention of tendon architecture changes was made.  I bet the tendon structure was improved in the PRP group (if a high enough platelet concentrate was used.)

This is a problem when a single study is touted as “being the gospel”. There’s more to the story

Excerpts from an article written by Yael Waknine appearing in Medscape January 13, 2010: ….The FDA has approved tocilizumab intravenous infusion (Actemra) for the once-monthly treatment of moderately to severely active rheumatoid arthritis (RA) in adults who have had an inadequate response to 1 or more tumor necrosis factor (TNF) antagonist therapies.

…Actemra is the first interleukin 6 receptor–inhibiting monoclonal antibody and may be used alone or in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARDS). It is expected to be available in the United States the week of January 18, 2010.

The recommended starting dose for tocilizumab is 4 mg/kg administered once every 4 weeks as a 60-minute single drip infusion, followed by an increase to 8 mg/kg based on clinical response.

Tocilizumab should not be used during active infection… Patients should be screened and treated for latent tuberculosis before starting treatment and monitored thereafter…

Because of the increased risk for infection, tocilizumab should not be used in combination with other biologic DMARDS, such as TNF inhibitors, IL-1 inhibiting drugs, B-cell depleters, and selective costimulation modulators (Basically, all other biologic groups).

Adverse events most commonly reported …include upper respiratory tract infection, nasopharyngitis, headache, high blood pressure, and liver enzyme elevations that were generally mild and reversible. Other laboratory changes, including increases in low-density lipoprotein cholesterol levels and decreased neutrophil and platelet counts, have also been observed and may require a decrease in dosage to 4 mg/kg. Serious adverse effects may include infection, gastrointestinal perforation, and hypersensitivity reactions, including anaphylaxis. As with other immunosuppressive therapies, tocilizumab may increase the risk for cancer.

Author’s note: This is a major advance for RA patients.  It is inconvenient as far as needing intravenous infusion. And there are many potential side effects to be on the lookout for.   Still it is a different mode of action and many patients who have failed other approaches may respond to this drug

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