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Diacerein in Hip Osteoarthritis
Diacerein in Hip Osteoarthritis
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Rikke H. Moe , Espen A. Haavardsholm, Anne Christie, Gro Jamtvedt, Kristin Thuve Dahm, Kåre Birger Hagen
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rikke.moe{at}nrrk.no Rikke H. Moe, et al.
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We thank Leeb and Rintelen for their comments on our article1 published in December 2007. As they point out, it was not evident that we should include diacerein in this umbrella review of nonpharmacological and nonsurgical interventions for hip osteoarthritis (OA). As the point out, it is a prescribed drug in several countries; however, in the majority of the European countries, including the Nordic region, this is not the case–and we thus chose to include it in this review. Diacerein is a diacetylated derivative of "rhein," which is the common name that describes the anthraquinone present in medicinal rhubarb (Rhei rhizoma). This plant (the root) has been used in China as a medicinal herb for thousands of years, and thus provides the background for using the term "herbal therapy" to describe diacerein. We agree that this term is not entirely precise, given the different status of the substance in various countries. Our umbrella review is only based on high-quality systematic reviews; primary studies were not considered in this process. As stated in our overview, "Adequate quantitative pooling of data in reviews was regarded as more valid than a qualitative data synthesis approach."1(p1720) We only included the part of the reviews with a quantitative pooling of patients who were diagnosed with hip OA. Thus, our analysis was based on the separate quantitative pooling for hip OA by Fidelix et al.2 We agree that it is not apparent that the information regarding included primary studies in Table 11(p1719) is based on 2 studies that address different outcomes; this could have been clarified by organizing the table differently. Based on the separate quantitative pooling for hip OA by Fidelix et al (Table 2, p 18),2 it appears that there might be a possible beneficial effect of diacerein on radiographic progression, with a relative risk of 0.84 (statistically significant); however, the absolute risk difference of -0.06 is not statistically significant. The review indicated marginal relative risk as well as inconsistent significance; therefore, we graded the results as low-quality evidence. Addressing the question on why we graded the effect of diacerein on pain, impairment, or incidence of total hip replacement as moderate-quality evidence for no effect; we analyzed the quantitative pooling for hip OA of Fidelix et al2 separately. The results showed no statistically significant difference in favor of diacerein on hip OA; heterogeneity was taken into account. We graded it as moderate-quality evidence, referring to Table 2: Grading Quality of Evidence1(p1721); the results are based on one updated systematic review of high quality that is based on at least one high-quality primary study. As Leeb and Rintelen point out, we are aware that Fidelix et al concluded that there is “gold”-level evidence that diacerein has a small, consistent benefit in pain improvement. However, this conclusion, as well as the effect estimates in the review by Rintelen et al,3 was based on effect estimates on both hip and knee OA, and not on a separate quantitative pooling for hip OA. Our conclusion is based solely on available data for hip OA. We think that one of the most important goals of an umbrella review is identifying items where more research is needed, and the effectiveness of diacerein on hip OA is one of the areas detected by this method. References 1 Moe RH, Haavardsholm EA, Christie A. Effectiveness of nonpharmacological and nonsurgical interventions for hip osteoarthritis: an umbrella review of high-quality systematic reviews. Phys Ther. 2007;87:1716-1727. 2 Fidelix TS, Soares BG, Trevisani VF. Diacerein for osteoarthritis. Cochrane Database Syst Rev. 2006;(1):CD005117. 3 Rintelen B, Neumann K, Leeb BF. A meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis. Arch Intern Med. 2006;166:1899-1906. |
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Burkhard F Leeb, MD State Hospital Stockerau, 1st and 2nd Dept. of Medicine, Center for Rheumatology, Lower Austria;, Bernhard Rintelen
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burkhard.leeb{at}stockerau.lknoe.at Burkhard F Leeb, et al.
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We read with great interest the paper by Moe et al published in the December issue.1 As authors of 1 of the 2 reviews on diacerein cited in the article,2 we, therefore, have a good knowledge of the data from the clinical trials of diacerein and we would like to comment on some misunderstandings concerning diacerein in this particular section of the article. First, diacerein, in our opinion, cannot be a considered a “herbal therapy” but is registered as a prescription drug in 25 countries, including several in the European Union. In contrast to the article, diacerein is, to our knowledge, not registered as a medication in the United States. This also holds true for chondroitin sulfate3 and glucosamine, which are registered prescription drugs in most European countries. Second, we do not understand why the authors state that the “conclusions from these reviews on the effect of Diacerein on hip [osteoarthritis] OA were based on 7 primary studies.”1(p1721) Of the 7 studies reviewed by Fidelix et al,4 3 were conducted only in patients with knee OA, 2 were conducted in patients with knee and hip OA, and 2 were conducted only in patients with hip OA. In our review, we included 2 clinical studies conducted only in patients with hip OA and 8 studies conducted in patients with hip and knee OA.2 In addition, the section on Diacerein in table 1 relating to the review by Fidelix et al appears to indicate that there were 6 placebo-controlled studies and 1 study versus nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with hip OA. It should be stated that these data refer to 2 clinical studies that investigated only patients with hip OA : one of them was a placebo-controlled, structure-modifying study of 3 years duration that included 507 patients,5 whereas the other was a double-blind, placebo- and naproxen-controlled study in 288 patients with hip OA.6 Furthermore, it remains unclear, why Moe et al conclude that there is “low-quality evidence” that treatment with diacerein reduces radiographic OA progression given that the placebo-controlled, structure-modifying study5 received a Jadad score7 of 5 in the review by Fidelix et al4 as well in ours,2 indicating that both groups of authors thought it was a high-quality study. Because only one structure-modifying study in patients with hip OA has been performed with diacerein and because the review by Fidelix et al,4 gave this study a Jadad score of 5, it appears evident that there is at least “moderate-quality evidence” that treatment with diacerein reduces radiographic OA progression according to the Table 2—Grading Quality of Evidence—in the article by Moe et al.1. Incidentally, in this structure-modifying study, the incidence of total hip replacement was a secondary efficacy parameter. The study was not sized to show a significant difference between groups for the incidence of total hip replacement.5 Last but not least, we do not understand why Moe et al, even citing the review by Fidelix et al, state that there is “moderate-quality evidence” that diacerein “has no effect on pain, impairment, or incidence of total hip replacement.”1(p1721) Indeed, Fidelix et al4 concluded that there is “gold”-level evidence that diacerein has a small, consistent benefit in pain improvement. In our meta-analysis, which was more extensive than the one by Fidelix et al, we summarized, that diacerein can be considered useful in the treatment of knee or hip OA, because we had found evidence diacerein was superior to placebo with respect to pain and function and equally effective compared with NSAIDS during the active treatment period.2 With respect to the folow-up period, diacerein was found to be significantly superior compared with NSAIDs concerning pain and function, indicating a carry-over effect of the drug once treatment was stopped.2 This has been confirmed by a recently published clinical study targeting particularly this carry-over effect.8 Burkhard F Leeb, MD; Bernhard Rintelen, MD 1st and 2nd Department of Medicine, Center for Rheumatology, Lower Austria; State Hospital Stockerau; Director: Prim. Dr. Burkhard F. Leeb; Karl Landsteiner-Institute for Clinical Rheumatology, A-2000 Stockerau, Landstrasse 18, Austria e-mail: burkhard.leeb@stockerau.lknoe.at References 1 Moe RH, Haarvardsholm EA, Christie A, et al. Effectiveness of nonpharmacological and nonsurgical interventions for hip osteoarthritis: an umbrella review of high-quality systematic reviews. Phys Ther. 2007;87:1716-1727. 2 Rintelen B, Neumann K, Leeb BF. A meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis. Arch Intern Med. 2006;166:1899-1906. Erratum in: Arch Intern Med. 2007;167:444. 3 Leeb BF, Schweitzer H, Montag K, Smolen JS. A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis. J Rheumatol. 2000;27:205-211. 4 Fidelix TS, Soares BG, Trevisani VF. Diacerein for osteoarthritis. Cochrane Database Syst Rev. 2006;(1):CD005117. 5 Dougados M, Nguyen M, Berdah L, et al; ECHODIAH Investigators Study Group. Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Evaluation of the Chondromodulating Effect of Diacerein in OA of the Hip. Arthritis Rheum. 2001;44:2539-2547. 6 Nguyen M, Dougados M, Berdah L, Amor B. Diacerhein in the treatment of osteoarthritis of the hip. Arthritis Rheum. 1994;37:529-536. 7 Jadad AR, Cook DJ, Browman GP. A guide to interpreting discordant systematic reviews. CMAJ. 1997;156:1411-1416. 8 Pavelka K, Trč T, Karpaš K, et al. The efficacy and safety of diacerein in the treatment of painful osteoarthritis of the knee: A randomized, multicenter, double-blind, placebo-controlled study with primary end points at two months after the end of a three-month treatment period. Arthritis Rheum. 2007;56:4055-4064. |
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