We read with great interest the American College of Rheumatology (ACR) 2012 recommendations for pharmacologic and nonpharmacologic management of osteoarthritis (OA) of the hand, hip, and knee recently published in Arthritis Care & Research (1). We would like to congratulate the authors for their outstanding work using an original approach (the Grades of Recommendation Assessment, Development and Evaluation approach), which is not only based on a review of the literature and expert opinion, but also provides a more comprehensive methodology and leads to recommendations that are clearly explicit (strong and conditional recommendations or no recommendations). Moreover, the recommendations do not simply focus on one localization of OA. These recommendations include only pharmacologic agents approved in North America and therefore, in a strict sense, could not be applied in other countries.
On behalf of the French Section on Osteoarthritis from the French Society of Rheumatology, we would like to share some comments. First, concerning hand OA, we believe it is important to distinguish between the treatment of OA in the proximal interphalangeal and distal interphalangeal joints from treatment of OA in the thumb base. Concerning the trapeziometacarpal joint, the ACR recommended not using intraarticular therapies. Indeed, the level of evidence for intraarticular injections in rhizarthrosis is weak (2). However, in daily practice, intraarticular injections of a corticosteroid (0.5 ml) for the treatment of flares in rhizarthrosis can be effective in patients with good tolerance and could be regarded as an alternate option before considering surgery.
Regarding long-term treatment in patients with interphalangeal joint OA, we do not understand why the authors distinguish hydroxychloroquine from methotrexate or sulfasalazine, since the level of evidence is not convincing for any of these drugs (3). Conversely, a recent well-designed randomized, placebo-controlled study on the treatment of hand OA with 800 mg of chondroitin sulphate (CS) showed a symptomatic benefit effect at 6 months (4).
Regardless of the localization of OA, we would like to comment on the so-called symptomatic slow-acting drugs in OA, which were not recommended by the ACR (CS and glucosamine) but have been recommended by other international scientific societies, such as the Osteoarthritis Research Society International and the European League Against Rheumatism (5, 6). First, as discussed by the authors, the preparations of CS and glucosamine, which are available without a prescription in the US, are certainly different from the preparations available in Europe. CS and glucosamine have been approved by the European Medicines Evaluation Agency. Some preparations have a drug status and are not solely classified as nutriceutical supplements. In addition, it is known that the purity of the drug molecules in the preparation is a key point and may differ greatly (7). Importantly, the level of activities of CS and of glucosamine in in vitro and in vivo animal studies is clearly linked to several biologic parameters, such as their purity, degree of sulfation for CS, and animal sources (7, 8).
Furthermore, it should also be considered that this category of compounds (including diacerein and avocado/soya extracts) may decrease the consumption of nonsteroidal antiinflammatory drugs (NSAIDs) and opioids, which are drugs with well-known severe side effects, particularly in the elderly (9). In other words, even if the molecules of drugs such as CS and glucosamine exhibit only a minor analgesic effect over placebo (and the placebo effect is known to be high in OA ), their sparing effect of reducing the intake of other drugs should be considered, including acetaminophen, for which there are now clear concerns regarding its cardiovascular and gastrointestinal safety profile.
The effect size of placebo on pain in knee OA is ∼0.5 and is clinically relevant at the individual level, reaching the minimum clinically important improvement in many patients (10, 11). This high placebo effect might explain the mild effect of some drugs in OA and the pitfalls in the interpretation of some meta-analyses performed in the field of OA (12). This high placebo effect should also be taken into account with regard to any intraarticular therapy in knee OA (10); it may explain why the efficacy of hyaluronic acid (HA) injections in knee OA remains controversial (1). However, at an individual level, we do believe that HA injections should be considered, especially in patients who do not respond to level 1 or 2 analgesics and/or NSAIDs, or are intolerant to these drugs, because the safety profile of HA injections is much better than that of NSAIDs or long-term use of opioids and/or the risk of knee surgery in elderly populations.
Although not strongly based on evidence-based medicine, for a chronic disease in which the armamentarium of treatments is rather limited, drugs with moderate effects but a good safety profile should always be considered and compared to drugs with better analgesic effects but a worse safety profile, in order to optimize the risk/benefit balance.
Finally, in an effort to establish recommendations in OA, one should always consider the patient's point of view. For instance, some patients with refractory hand OA develop a perception that they are being neglected by the medical staff (13), which may be a situation that simply reflects the practioner's perception that not much can be done.
Dr. Chevalier has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Expanscience, Genevrier, IBSA, Pierre Fabre, Negma, Sanofi, Servier, and Smith & Nephew. Dr. Richette has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Bioiberica, Expanscience, Fidia, Genevrier, Negma, and Servier. Dr. Sellam has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Abbott, Bristol-Myers Squibb, MSD, Pfizer, and Roche. Dr. Maheu has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Expanscience, Genzyme, IBSA, Pierre Fabre, and Rottapharm. Dr. Conrozier has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Labrha, Sanofi, Smith & Nephew, and Rottapharm.