The Research
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The Treatment of Arthritis

Amitriptyline is Better than Trazodone or Desipramine for Arthritis Pain: In a 47-patient DB PC crossover study, amitriptyline did better than trazodone, desipramine, or placebo. Antidepressant analgesia in rheumatoid arthritis. Frank RG, Kashani JH, et al. J Rheumatol 1988 Nov;15(11):1632-8

Anakinra New Rheumatoid Arthritis Med: Anakinra is similar to an interleukin-1 receptor antagonist (IL-1Ra).  Interleukin-1 (IL-1) is produced in excess in RA patients and damages joints. Anakinra blocks IL-1. It's made by Amgen.  Ed: This medicine is very expensive and has never been compared to much less expensive and possibly more effective strategies.

Antibodies Predict Onset of Rheumatoid Arthritis: Anticyclic citrullinated peptide (CCP) and IgA-rheumatoid factor are highly predictive of the development of rheumatoid arthritis. At more than 1.5 years before appearance of symptoms, sensitivity was 25% for anti-CCP, 15% for IgM-RF, 12% for IgG-RF, and 29% for IgA-RF. At 1.5 years or less before symptom onset, sensitivities were 52%, 30%, 27%, and 39%, respectively.. Rantapaa-anti-CCF with IgA-RF had a predictive value of 99%. Arthritis Rheum. 2003;48:2741-2749, Umea Univ, Sweden

Antibodies: Glycosaminoglycan Said Immune Target in RA: Harvard research. Arthritis Today 1/03

Antibodies: Osteoarthritis Also has an Autoimmune Component: In a study of 117 OA and 94 RA Japanese patients, 11% of each group had antibodies to YKL-39, a protein in cartilage. J Rheum 29(7) 7/02.

Bacterial Infections May Lead to RA: RA patients had significantly elevated IgG antibodies to P gingivalis ( P < .001), P intermedia ( P < .001), P melaninogenica ( P < .01), and B forsythus ( P < .05) when compared with healthy controls. A positive correlation between serum IgG antibody levels against P gingivalis and serum CRP was clearly detected in patients with RA ( r = .795; P = .000; Figure 1). There was significant correlation between serum IgG antibody levels against P intermedia and ESR ( r = .809; P = .000). Gingival tissue infections should be considered in RA pathogenesis. Periodontal infections should be treated and prevented from becoming chronic. Serum Antibodies to Oral Anaerobic Bacteria in Patients With Rheumatoid Arthritis. Ogrendik et al. GenMedGen 2005;7(2).

Bisphonates Increase Bone Density in Rheumatoid Patients on Steroids: In a DB PC study of 163 Rheumatoid arthritis patients on low-dose prednisone (</=10 mg/day) for at least 3 months, 5 mg alendronate, after 3 months, serum BAP had decreased by 17% for alendronate vs. 3.3% for placebo (p=0.0005), while urinary NTX had decreased by 46% in the alendronate group versus 12% in the placebo group (p<0.0001). There was no difference in fractures the first 12 months. All received calcium 500-1000 mg/d plus vitamin D 400 units. Positive effect of alendronate on bone mineral density and markers of bone turnover in patients with rheumatoid arthritis on chronic treatment with low-dose prednisone: a randomized, double-blind, placebo-controlled trial. Lems WF. VU University, Amsterdam, The Netherlands. Osteoporosis Int 2006 Feb 3;1-8. Ed: Even low dose predisone can cause osteoporosis.  However, vitamin K 1 mg/day would seem much more cost effective.

Borage Oil: Oils enriched in certain PUFAs suppress joint pain and swelling in RA. T lymphocyte activation important in propagation of joint tissue injury in RA. 2.4 g gammalinolenic acid in borage seed oil reduced T cell prolif. Oils rich in linoleic and alpha linolenic did not influence growth of stimulated cells. Rossette RG, U Mass Worcester, J Leukoc Biol 1997 Oct;62(4):438-43. See evening primrose below for lack of benefit. 

Borage Helped RA: In a study of 1.4 g/d of GLA vs. a cotton seed placebo, this study found 36%-45% decreases in tender joints, swollen joints, and degree of pain. Leventhal, U Penn, Ann Intern Med 11/1/93;119:867-73

Boswellia Some Help for Osteoarthritis: In a 30-patient DB PC crossover study of osteoarthritis of the knee, boswellia was given for eight weeks. Osteoarthritis is a common, chronic, progressive, skeletal, degenerative disorder, which commonly affects the knee joint. Boswellia serrata tree is commonly found in India. The therapeutic value of its gum (guggulu) has anti-inflammatory, anti-arthritic and analgesic activity. All patients reported decrease in knee pain, increased knee flexion, swelling, and increased walking distance on boswellia. Radiologically there was no change. There were only minor GI side-effects. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial. Kimmatkar N, Thawani V, Hingorani L, Khiyani R. Indira Gandhi Medical College. Phytomedicine. 2003 Jan;10(1):3-7. Cost is about $13 per month.

Boswellia No Help for Rheumatoid Arthritis: In a 37-patient DB PC study using 9 tablets of active drug (3600 mg) or placebo daily, there was no subjective, clinical or laboratory parameter showing a significant benefit. Is H15 (resin extract of Boswellia serrata, "incense") a useful supplement to established drug therapy of chronic polyarthritis? Results of a double-blind pilot study. Sander O, Herborn G, Rau R. Evangelisches Fachkrankenhaus Ratingen. Z Rheumatol. 1998 Feb;57(1):11-6

Boswellia-Curcumin-Zinc-Withania Concoction Helped Osteoarthritis: In a one-month 42-patient DB PC cross-over study with a 15-day washout between crossover, clinical efficacy was evaluated every fortnight on the basis of severity of pain, morning stiffness, Ritchie articular index, joint score, disability score and grip strength. Treatment with the herbomineral formulation produced a significant drop in severity of pain (P less than 0.001) and disability score (P less than 0.05). Radiological assessment, however, did not show any significant changes. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. Kulkarni RR, Patki PS, et al. University of Poona. J Ethnopharmacol. 1991 May-Jun;33(1-2):91-5

Cat's Claw Extract May Help Rheumatoid Arthritis: In a 24 week DB PC study of 40 adults with rheumatoid arthritis undergoing sulfasalazine or hydroxychloroquine treatment were enrolled in a randomized 52 week, those on Uncaria tomentosa (UT) had a reduction of the number of painful joints compared to placebo (53% vs 24%; p = 0.044). Patients receiving the UT extract only during the second 24-week phase experienced a reduction in the number of painful (p = 0.003) and swollen joints (p = 0.007) and the Ritchie Index (p = 0.004) compared to the values after 24 weeks of placebo. Only minor side effects were observed. Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of uncaria tomentosa for the treatment of rheumatoid arthritis. Mur E, et al. Innsbruck University Hospital, Austria. . J Rheumatol. 2002 Apr;29(4):678-81. Ed: Cat's claw (una de gato) is a Peruvian plant popular in Latin American folk medicine for arthritis, gastritis, etc. 

Cat's Claw May Help Osteoarthritis: In a 4-week DB PC study of 45 patients with osteoarthritis of the knee, those treated with freeze-dried U guianensis had pain associated with activity, medical and patient assessment scores significantly reduced, with benefits occurring within the first week of therapy. Knee pain at rest or at night, and knee circumference were not significantly reduced by cat's claw during this brief trial. In vitro tests indicated that U guianensis and U. tomentosa were equivalent at quenching DPPH radicals (EC50, 13.6-21.7 microg/ml) as well as inhibiting TNFalpha production. However, the latter action was registered at much lower concentrations (EC50, 10.2-10.9 ng/ml). Cat's claw (10 microg/ml) had no effect on basal PGE2 production, but reduced LPS-induced PGE2 release (P < 0.05), but at higher concentrations than that required for TNFalpha inhibition. Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Piscoya J, et al. Universidad Nacional Mayor de San Marcos, Lima, Peru. Inflamm Res. 2001 Sep;50(9):442-8.

Coffee Linked to Rheumatoid Arthritis (RA): 18,981 Finnish adults followed up to 19 years. Those drinking over 3 cups coffee per day had twice rate of rheumatoid arthritis (.08%) as those drinking less. Annals Rheu Dis 8/00

Coffee OK but not Decaf: University of Alabama at Birmingham and reported to the American College of Rheumatology Annual Scientific Meeting in San Francisco concluded that some decaffeinated beverages may actually increase the risk of developing rheumatoid arthritis. Some 2.1 million Americans, most of whom are women, are afflicted with this incurable autoimmune disease. They suffer from painful inflammation of the joints and internal organs. Reuters reports this new research profiled more than 31,000 women aged 55 to 69, and those who drank four or more cups of decaffeinated coffee a day were more than twice as likely to develop rheumatoid arthritis, compared to those who never drank decaf. Note this: There is no link between regular coffee and an increased risk of rheumatoid arthritis. 11/12/01

Coffee: Decaf Increases RA, Not Regular Coffee: 31,000 Iowa women ages 55-69 were followed. Over 3 cups decaf doubled rheumatoid arthritis, but not tea or regular coffee. Arth and Rheum 44:S375 ’02.

Cod Liver Oil Didn’t Help Osteoarthritis: A DB PC study of 86 patients given 10 ml cod liver oil or placebo for 24 weeks in addition to their regular NSAID and assessed every 4 weeks found no difference in pain, inflammation, or other benefit. St. George’s Hosp. Efficacy of cod liver oil as an adjunct to non-steroidal anti-inflammatory drug treatment in the management of osteoarthritis in general practice. Ann Rheum Dis 1992;51:128-9; In the 1700s, cod liver oil was routinely given to arthritis patients at the Manchester, England hospital to "oil their joints." www.lysi.is.  

COX-2 Inhibitors Expensive with No Real Advantage: Celebrex is a patented medicine for osteo and RA. It is a selective COX-2 inhibitor and is promoted over much cheaper medicines because it is supposed to cause fewer stomach ulcers. Cyclooxygenase enzyme (COX) is required for synthesis prostaglandins and thromboxanes. COX-1 thought to protect gastric mucosa and in platelets. COX-2 is found in brain, kidney, and sites of inflammation. Both are in synovial fluid. Celebrex supposedly doesn't affect the COX-1 in the stomach significantly so it shouldn't cause ulcers.  Celebrex 100-200 mg BID costs $86 for lowest dosage vs. ibuprofen $3, naproxen $8, diclofenac (Voltaren) $55. It is metabolized by CYP2C9 and inhibits 2D6 and may increase some antidepressants and antipsychotics. Dosages up to 400 BID are OK ($344/mo.). After 12 weeks, ulcers appeared in 7% on Celebrex vs. 10% declofenac, 35% naproxen 500 BID, 23% ibuprofen 800 tid, 4% placebo. However, after 1 year, cumulative UGI perforations, clinically significant ulcers and bleeds occurred to 1.3% on rofecoxib vs. 1.8% other NSAIDs (JAMA 282:1929, 1999). Not a clear advantage (Ann Intern Med 2000;132:134). Rofecoxib (Vioxx)($72) 25-50 mg QD caused an increase death rate and was withdrawn from the market in November, 2004. COX-2 inhibitor may be prothrombotic leading to higher incidence cardiovascular events (Med Let 7/10/00). No mention of evidence that help with AD. (Ed: In other words, these highly expensive COX-2 inhibitors are simply not worth the huge amounts of money being spent on them. I would try to avoid all NSAIDs if at all possible.)

Debridement and Lavage No Benefit for Knee OA: In a 180-patient DB study of a common type of surgery given to 650,000 people per year in U.S., researchers found it is of no benefit despite a cost of $5,000 per treatment! NEJM 7/11/02. Houston VA

Diet: Supplementary C, E, Zinc and Fruits, Cruciferous Vegetables Linked to Lower Rheumatoid Arthritis: A nationwide Mayo Clinic study of 29,368 women followed for 11 years found benefit from vitamin C, E, zinc, fruits, and cruciferous vegetables. Antioxidant micronutrients and risk of rheumatoid arthritis in a cohort of older women. Cerhan JR, Saag KG, Merlino LA, Mikuls TR, Criswell LA. Am J Epidemiol. 2003 Feb 15;157(4):345-54

Diet: Olive Oil & Cooked Vegetables Protect Against RA: A Greek study from the University of Athens with a case-control methodology found those with lowest intake olive oil had 2.5 times the risk of RA as those with highest intake.  Those with the lowest intake cooked vegetables had 75% higher risk. Am J Clin Nutr 1999; 70: 1077-82.

Doxycycline Helps: Ten randomized controlled trials including 535 individuals were found. Tetracyclines, when administered for at least 3 months, were associated with a significant reduction in disease activity in rheumatoid arthritis as follows: for tender joint count (TJC), standardized mean difference (SMD) = -0.39; and for acute phase reactants, ESR, SMD = -8.96. The treatment effect was more marked in the subgroup of patients with disease duration of less than 1 year who were seropositive. There was no absolute increased risk of adverse events associated with tetracyclines. No beneficial effect was seen on radiological progression of disease: for erosions, SMD = 0.17. Longer acting tetracyclines doxycycline and minocycline worked better. Should tetracycline treatment be used more extensively for rheumatoid arthritis? Metaanalysis demonstrates clinical benefit with reduction in disease activity. Stone M, Fortin PR, Pacheco-Tena C, Inman RD. Toronto Western Hospital. J Rheumatol. 2003 Oct;30(10):2112-22. Ed: Doxycycline is very inexpensive.

Early Treatment of Rheumatoid Arthritis Better: All patients were started on analgesics. The median lag to the initiation of disease-modifying chloroquine or salazopyrine treatment was 15 days in the early treatment group and 123 days in the delayed treatment group. There was less radiologic joint damage after 2 years in the early treatment group (median Sharp score, 3.5) compared with the delayed treatment group (median Sharp score, 10; P <0.05). Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Lard LR, Visser H, Speyer I, vander Horst-Bruinsma IE, Zwinderman AH, Breedveld FC, Hazes JM. Leiden University, The Netherlands. Am J Med. 2001 Oct 15;111(6):446-51

Enbrel & Remicade Stop Damage: Enbrel injections BIW alone or adding remicade to methotrexate were found to slow tissue damage and have fewer side-effects than methotrexate in new cases. Cost is $10-12,000/yr. NEJM 10/29/00. Ed: These extremely expensive medications were never tried first on the many healthy, low cost alternative listed above. Drug companies are out to maximize profits, not help people.

Etanercept (Immunex), Infliximab (Remicade), & Adalimumab (Humira) SC or IV Block Tumor Necrosis Factor: TNF is one of the cytokines responsible for the inflammation of RA for those refractory to methotrexate. These are usually added to methotrexate at a cost of $15,680 for 12 months treatment. They are somewhat helpful, but can cause lymphoma, lupus, and CHF. They do inhibit disease progression. Ed.: Hugely expensive medicines like these will be way over-used and needlessly spend national resources. There are many inexpensive alternatives as well as dietary interventions.

Evening Primrose No Better than Olive Oil for RA: In a DB PC study using 540 g/day of GLA for 40 patients over 6 months, no benefit was found over olive oil, which is a lot cheaper. Glasgow, Br J Rheumatol 10/91 Brzeski

Exercise OK for Arthritis Sufferers: A Dutch study of 300 people with rheumatoid arthritis for two years put half in a one-hour exercise regimen twice weekly; the rest received traditional treatment, including physical therapy. Arthritis & Rheumatism, 9/03 Thea P.M. Vliet Vlieland of Leiden University. Prolonged, rigorous exercise had no significant detrimental effect on weight-bearing joints, except in cases of patients who already had considerable large joint damage. The exercise group did better emotionally and physically although there was no difference in arthritis pain or number of pain meds taken.

Fish Oil Helps RA in 7 DB studies: A meta-analysis of 7 DB PC studies of 395 patients found that after 3 months, there was a decrease in tender joints and a decrease in morning stiffness. Fortin, Harvard, J Clin Epidem 11/95;48:1379

Fish Oil with Olive Oil Helped Rheumatoid Arthritis: In a 24-week DB PC study of 43 rheumatoid arthritis victims, fish oil omega-3 fatty acids (3 g/d) led to a statistically significant improvement (P < 0.05) in joint pain intensity, right and left handgrip strength after 12 and 24 wk, duration of morning stiffness, onset of fatigue, Ritchie's articular index for pain joints after 24 wk, ability to bend down to pick up clothing from the floor, and getting in and out of a car after 24 wk. However, there was a more precocious and accentuated improvement when fish oil supplements were used in combination with olive oil 9.6 mL. Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Berbert AA, Kondo CR, et al. Londrina State University, Parana, Brazil. Nutrition. 2005 Feb;21(2):131-6

Fish Oil Recommend Omega-3: LG Cleland in editorial in Brit J Rheum (5/97;36:513-4) says evidence high omega-6 and low omega-3 increases blood clots, arrhythmias, and inflammatory disorders like RA. He says humans evolved on 2:1 ratio and not the current 25:1 in the diets of most people. Omega-6 eicosanoids promote inflammation while omega-3 retard it. He reports that fish oil is an anti-inflammatory and a high ALA diet reduces synthesis of interleukin (IL-1 beta) and tumor necrosis factor alpha.

Flax Seeds Didn't Help RA: In a 3 month random study vs. sunflower seeds, no decrease pain was found. Neither AA, EPA, nor DHA changed. Rheum Int ’95 14:231-4. Nordstrom DC. 

Folate Added to Methotrexate Helps: In a DB PC study of folate added to methotrexate treatment of rheumatoid arthritis, researchers found that folate helped reduce toxicity without impairing the benefit for RA. Ann Intern Med ’94;121:833

Folate and B-12 Help OA: In a DB PC study of 27 patients with 6 years of osteo treatment with NSAID, patients were treated with folate 6400 microg/d and B-12 20 microg/d for 3 weeks or placebo. Grip was better with vitamins and equal to NSAID while there fewer tender joints with vitamins than with NSAID and far fewer side-effects. Flynn, U Missouri, J Am Coll Nutr 8/94;13:351 (Ed: This is an unusually high dose of folate.  I would recommend just 800-1600 microg/day or one or two 800 microg pills until research shows some advantage to such a high dose, although the higher dose is perfectly safe.) 

Ginger Might Help: Ginger is a traditional Indian remedy for arthritis. In a DB PC crossover study of 29 adults with  gonarthritis, each group received 250 mg four times a day of ginger in capsules for three months with half getting the ginger in the first 3 months and the others in the second 3 months. Two dropped out during ginger administration due to heartburn. By the end of 24 weeks there was a highly statistically significant difference between the VAS of pain and handicap favoring ginger (P<0.001). However, this benefit did not show up during the first 3 months, possibly due to a high improvement in the placebo group. The effects of Zintona EC (a ginger extract) on symptomatic gonarthritis. Wigler I, Grotto I, et al. Tel Aviv University,  Israel. Osteoarthritis Cartilage. 2003 Nov;11(11):783-9. Ed: The study clearly needs to be repeated.

Ginger Helped: In a large 6-week DB PC study of 247 osteoarthritis sufferers, ginger (Zingiber officinale and Alpinia galanga (EV.EXT 77)) twice a day (probably 500 mg) had more reporting a reduction in "knee pain on standing," using an intent-to-treat analysis (63% vs. 50%; P = 0.048). Ginger did better for reduction in knee pain on standing on pain scale estimates (24.5 mm vs. 16.4 mm; P = 0.005), reduction in knee pain after walking 50 feet (15.1 mm vs. 8.7 mm; P = 0.016), and reduction in the osteoarthritis composite index (12.9 mm vs. 9.0 mm; P = 0.087). Change in global status and reduction in intake of rescue medication (Tylenol) were numerically greater in the ginger extract group. Change in quality of life was equal in the 2 groups. Patients receiving ginger extract experienced more gastrointestinal (GI) adverse events than did the placebo group (59 patients versu.s. 21). GI adverse events were mostly mild. Effects of a ginger extract on knee pain in patients with osteoarthritis. Altman RD, Marcussen KC. University of Miami, Florida, USA. Arthritis Rheum. 2001 Nov;44(11):2531-8.

Ginger Benefit Weak: In a brief DB PC crossover study with patients on ginger for 3 weeks, ibuprofen for 3 weeks and placebo for 3 weeks with 1 week washouts, ibuprofen did clearly better for pain relief with ginger only somewhat better than placebo (P< 0.00001). A randomized, placebo-controlled, cross-over study of ginger extracts and ibuprofen in osteoarthritis. Bliddal H, Rosetzsky A, et al. Frederiksberg Hospital, Copenhagen, Denmark. Osteoarthritis Cartilage. 2000 Jan;8(1):9-12.

Ginger Used for Arthritis and Muscular Discomfort: In a non-scientific open report of 56 patients (28 with rheumatoid arthritis, 18 with osteoarthritis and 10 with muscular discomfort) using powdered ginger, more than three-quarters of arthritis patients reported, to varying degrees, relief in pain and swelling. All the patients with muscular discomfort experienced relief in pain. None reported adverse effects during the period of ginger consumption which ranged from 3 months to 2.5 years. Ginger inhibits prostaglandin and leukotriene biosynthesis. Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders. Srivastava KC, Mustafa T., Odense University, Denmark. Med Hypotheses. 1992 Dec;39(4):342-8. Ed: Powdered ginger can be purchased very cheaply in some Oriental food stores. 1 g/day is about 1/2 teaspoon.  This can easily be added to food and may cause less gastritis that way, if the above report is correct.

Gold Still Useful for Rheumatoid Arthritis: The oldest conventional disease-modifying antirheumatic drug (DMARD), injectable gold (Au), which was introduced in the 1920s. The effect of gold is directed at a number of different sites of the immune system. A significant improvement of clinical and biochemical disease activity parameters as well as an inhibition of X-ray progression has been shown in many studies. Head-to-head comparisons between gold and high-dose methotrexate (MTX) demonstrated no significant difference but some advantages for gold. Researchers selected four trials with gold (two open, one placebo-controlled, and one comparison with MTX) and five trials with biologics (three placebo-controlled, one dose escalation study, and one comparison with MTX). In all these trials baseline data regarding swollen joint count (SJC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were roughly comparable and, with the exception of interleukin (IL)-1 RA, demonstrated a similar improvement of over 50% already after 6 months [with faster onset with tumor necrosis factor (TNF)-alpha blockade]. European League Against Rheumatism (EULAR) response criteria could be calculated for the Au/MTX trial and were-for these compounds-only slightly inferior to the results with adalimumab. X-ray response is especially difficult to compare across studies. Although an inhibition with Au and MTX could be demonstrated, this occurred-similar to corticosteroid treatment-earlier and more pronounced with TNF-alpha blockers. The most modern DMARDs do not appear to be much better than the oldest one indicating that conventional DMARDs are not outdated. Therefore, a sufficient trial of conventional DMARDs should precede the introduction of treatment with the very expensive biologics. Have traditional DMARDs had their day? Effectiveness of parenteral gold compared to biologic agents. Rau R. Ratingen, Germany. Clin Rheumatol. 2005 Jun;24(3):189-202.

Green Tea Helps Mouse Arthritis: Polyphenols, isolated from green tea which contains higher amounts than black tea, decreased mouse arthritis produced by injecting a substance to imitate RA. Virtually no cartilage damage occurred in polyphenol mice although it was present in controls. Far fewer immune-system cells were found in polyphenol mice. Tariq Haqqi, Case Western, Proceedings of the Natl Acad Sci 4/13/99 & Sci News 4/17/99.

High Heels: Wide or Narrow, Both Cause Knee Osteoarthritis: Both were just as likely to cause arthritis, since clunky ones are worn longer.  Once arthritis pain occurs, its too late to prevent osteoarthritis. Kerrigan, Harvard, Lancet 4/4/01.

Hyaluronan Injections Little Value for Knee OA: Sodium hyalurone (Hyalgan) and hylan G-F 20 weekly injections for 5 or 3 weeks cost over $600 and minimally better than NSAID or even placebo. Various side-effect with infection, pain, arthritis. Med Let 7/3/98

Infliximab Modest Benefit: In a DB PC study of 1049 patients with rheumatoid arthritis receiving methotrexate ( MTX )-placebo, MTX -3 mg/kg infliximab, and MTX -6 mg/kg infliximab, at week 54 the median percentage of improvement was higher for the MTX -3 mg/kg infliximab and MTX -6 mg/kg infliximab groups than for the MTX -placebo group (38.9% and 46.7% versus 26.4%, respectively; P < 0.001) with less radiographic progression than those receiving MTX alone (0.4 and 0.5 versus 3.7, respectively; P < 0.001). Infliximab therapy was associated with a significantly higher incidence of serious infections, especially pneumonia. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: A randomized, controlled trial. St Clair EW, van der Heijde DM, et al. Duke University . Arthritis Rheum. 2004 Nov 4;50(11):3432-3443

Infliximab anti-TNF monoclonal Antibody: Also used for methotrexate refractory. Cost $3500-10500 for three doses. Given IV Q4-12weeks. Med Let 11/20/98

Leflunomide Inhibits Pyrimidine Synthesis: Alternative to methotrexate ($300/6 mo). Slows RA joint deterioration but doesn’t stop it. $1600/6mo. Med Letter says methotrexate is as effective (7/10/00).

Magnets: Knee and Hip Osteoarthritis Pain Helped: In a 194-patient, 12-week DB PC study of osteoarthritis pain of the knee and hip using a standard strength static bipolar magnetic bracelet, a weak magnetic bracelet, or a non-magnetic (dummy) bracelet, mean pain scores were reduced significantly more in the standard magnet group than in the dummy group (1.3 points). Patients before starting the study had 8-20 points of pain on the WOMAC A scale. This benefit was not quite as large as reported in some NSAID pain med trials, but was considered in the same range and of clinical significance. For instance, an important study using a COX-2 inhibitors, the middle strength caused a 1.5 point decrease in pain over the placebo and the high strength a 1.9 point decrease. Of course, COX-2 inhibitors cause an increased death rate and this appears unlikely for wrist bracelets. Self reported blinding status did not affect the results. The scores for secondary outcome measures were consistent with the pain scores. Randomised controlled trial of magnetic bracelets for relieving pain in osteoarthritis of the hip and knee. Harlow T, Greaves C, et al. College Surgery, Cullompton, UK. BMJ. 2004 Dec 18;329(7480):1450-4.

Motor Oil Increased Risk of Rheumatoid Arthritis: In a study of 135 men with RA and 132 controls, motor and hydralic oil exposure raised the risk of RA among men by 30 percent. This exposure only increased the risk of RA in subjects positive for rheumatoid factor and anti-citrulline, blood tests used to help diagnose RA. Berit Sverdrup, et al. Karolinska Hospital, Stockholm, Sweden. Arthritis Research & Therapy, September 23, 2005.

Mud Compresses Actually Found to Work for Rheumatoid Arthritis: In a 45-patient DB study of mud compresses five times a week for three weeks vs. attenuated mud compresses, the real thing resulted in a decrease in swollen and tender joints. The benefits were still measurable 3 months later. Mud compress therapy for the hands of patients with rheumatoid arthritis. Ben Gurion Univ. Codish S, Abu-Shakra M, Flusser D, Friger M, Sukenik S. Rheumatol Int. 2003 Nov 14. 

Niacinamide Helps OA a Little:  In a DB study of 12 weeks covering 72 patients with OA, niacinamide led to decreases in sed rate, increases in range of motion, decreases in pain meds, and better overall by 29%. Inflamm Res 1996 Jul;45(7):330-4

Niacinamide Helped: A recent double-blind study confirms the efficacy of niacinamide in OA. It may be feasible to interpret this finding in the context of evidence that synovium-generated interleukin-1 (IL-1), by inducing nitric oxide (NO) synthase and thereby inhibiting chondrocyte synthesis of aggrecan and type II collagen, is crucial to the pathogenesis of OA. Niacinamide and other inhibitors of ADP-ribosylation have been shown to suppress cytokine-mediated induction of NO synthase in a number of types of cells; it is therefore reasonable to speculate that niacinamide will have a comparable effect in IL-1-exposed chondrocytes, blunting the anti-anabolic impact of IL-1. The chondroprotective antibiotic doxycycline may have a similar mechanism of action. Other nutrients reported to be useful in OA may likewise intervene in the activity or synthesis of IL-1. Supplemental glucosamine can be expected to stimulate synovial synthesis of hyaluronic acid; hyaluronic acid suppresses the anti-catabolic effect of IL-1 in chondrocyte cell cultures, and has documented therapeutic efficacy when injected intra-articularly. S-adenosylmethionine (SAM), another proven therapy for OA, upregulates the proteoglycan synthesis of chondrocytes, perhaps because it functions physiologically as a signal of sulfur availability. IL-1 is likely to decrease SAM levels in chondrocytes; supplemental SAM may compensate for this deficit. Adequate selenium nutrition may down-regulate cytokine signaling, and ample intakes of fish oil can be expected to decrease synovial IL-1 production; these nutrients should receive further evaluation in OA. McCarty MF. Med Hypotheses 1999 Oct;53(4):350-60 

NSAIDs: Ibuprofen, Naproxen, Cox-2 Inhibitors, Others Bad for Arthritis Sufferers: In a meta-analysis of 23 DB PC studies totaling 10,845 patients with osteoarthritis of the knee and treated with either NSAID drugs (e.g. ibuprofen, naproxen, coxibs, etc.), researchers found evidence for only a small short-term benefit and no evidence for any long-term benefits.  It appeared that few if any of the studies lasted over 13 weeks even though patients typically take these drugs for many years.  The average age of the patients was 62 and had been suffering for an average of over 8 years.  Thus, any small short-term benefits may be outweighed by the serious side-effects.  NSAIDs lead to ulcers, high blood pressure, congestive heart failure, kidney failure, and early death.  They can interfere with lithium excretion. Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials. Jan Magnus Bjordal et al. Univ. of Bergen, Norway. BMJ  12/4/2004;329:1317. Ed: Ibuprofen and others should be used for short term pain relief only.

New Drugs: Med Letter 11/10/98. Leflunomide (Arava) $1600 vs. $300 for methotrexate for 6 mo. It inhibits pyrimidine synthesis with an antiproliferative effect on T-cells and an anti-inflammatory effect. It was better than methotrexate and sulfasalazine (Azulfadine), markedly slowing progression and improving functional status after two years. Diarrhea, rash, and alopecia side-effects. Women must use cholestryramine to it get out of their system before attempting pregnancy. Etanercept (Enbrel) blocks tumor necrosis factor, a major cytokine responsible for the inflammation of RA. It is a recombinant version of the human TNF receptor. Infliximab (Remicade) is a chimeric human/mouse anti-TNF monoclonal antibody. Both are good and infliximab somewhat additive to methotrexate but extremely expensive at $6300/6 mo. It is not known if it slows disease or has long term side-effects.

Physiotherapy No Benefit for Osteoarthritis: In a 24-week DB PC study of 140 patients with knee osteoarthritis, physiotherapy including 12 weeks of exercise, massage, taping, and mobilisation, followed by 12 weeks of self management had no significant benefit. Placebo was sham ultrasound and light application of a non-therapeutic gel, followed by no treatment. Primary outcomes were pain measured by visual analogue scale and patient global change. Secondary measures included WOMAC, knee pain scale, SF-36, assessment of quality of life index, quadriceps strength, and balance test. Efficacy of physiotherapy management of knee joint osteoarthritis: a randomised, double blind, placebo controlled trial. Bennell KL, Hinman RS, et al. University of Melbourne, Australia. Ann Rheum Dis. 2005 Jun;64(6):906-12.

Pioglitazone (Actos), a peroxisome proliferator-activated receptor gamma agonist, reduces the progression of experimental osteoarthritis in guinea pigs: Kobayashi T, et al. Osaka, Japan. Arthritis Rheum. 2005 Feb;52(2):479-87. Actos is a fairly expensive diabetes medication.

Prosorba Column New Treatment for RA: Used for ITP since 1987, doctors noticed RA patients were helped. Phase III trial stopped early due to marked benefit with half of patients having significant benefit. Blood is circulated through column 2 hours a week for 12 weeks. It may bind immune complexes and antibodies. Lancet 3/27/99

Risedronate (Actonel) Helped Knee Osteoarthritis: In a 1-year DB PC study of 284 patients with mild to moderate OA of the medial compartment of the knee, those receiving risedronate at 15 mg showed improvement of the WOMAC index, particularly of physical function, significant improvement of the patient global assessment (P < 0.001), and decreased use of walking aids relative to patients receiving the placebo (P = 0.009). A trend towards less joint-space narrowing was observed in the group receiving 15 mg risedronate. Eight percent of patients on placebo and 4% on 5 mg risedronate had detectable progression of disease (joint-space width >or= 25% or >or= 0.75 mm) versus 1% on 15 mg risedronate (P = 0.067). Risedronate (15 mg) significantly reduced markers of cartilage degradation and bone resorption. Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173]. Spector TD, Conaghan PG, et al. St Thomas' Hospital, London, UK. Arthritis Res Ther. 2005;7(3):R625-33.

Rutosid-Bromelain-Trypsin Combo Helps Osteoarthritis: In a 6-week 103 patient study of an oral enzyme-rutosid combination (ERC) containing rutosid and the enzymes bromelain and trypsin vs. the NSAID diclofenac in patients with osteoarthritis (OA) of the knee, the LFI measure of functional impairment decreased from 13.0 to 9.4 in the ERC group and from 12.5 to 9.4 in the diclofenac group. Considerable improvements were also seen in secondary efficacy criteria, with a slight tendency towards superiority of ERC. The global judgment of efficacy by physician resulted in at least good ratings for 51.4% of the ERC patients, and for 37.2% of the diclofenac patients. Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee - a double-blind prospective randomized study. Akhtar NM, Naseer R, Farooqi AZ, Aziz W, Nazir M. Pakistan King Edward Medical College. Clin Rheumatol. 2004 Jul 24. Ed: The combo is available via internet at 25 cents a tablet (Wobenzym). Wobenzym is an enzyme formula manufactured in Europe by Mucos GMBH. Pancreatin (8 X) 100 mg equal to 800 mg pancreatin USP). Trypsin (720 FIP) 24 mg, Chymotrypsin (300 FIP) 1 mg, Bromelain (225 FIP) 45 mg, Papain (164 FIP) 60 mg, and Rutosid-3 H20 50 mg.

Statin Seems to Help Rheumatoid Arthritis: In a DB PC study of 116 patients with rheumatoid arthritis, those given 40 mg atorvastatin a day over 6 months had significantly improved disease activity scores on atorvastatin (-0.5) compared with placebo (0.03, p=0.004). C-reactive protein and erythrocyte sedimentation rate declined by 50% and 28%, respectively, relative to placebo (p<0.0001, p=0.005). Swollen joint count also fell (-2.69 vs. -0.53; p=0.0058). Adverse events occurred with similar frequency in patients allocated atorvastatin and placebo. Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, Ford I, Capell HA, Sattar N. University of Glasgow, Lancet. 2004 Jun 19;363(9426):2015-21. 

Tetracyclines Help Rheumatoid Arthritis: In a DB 26-week 80-patient study with active rheumatoid arthritis treatment with minocycline up to 200mg/day vs. placebo found pronounced improvement in lab values with lesser improvement in clinical parameters with minocycline. Some GI symptoms and dizziness. Other research shows tetracyclines of benefit in rat chronic arthritis and adjuvant arthritis. Also helped experimentally induced canine osteoarthritis. Also 3 open and two controlled human studies showing of benefit for RA and reactive arthritis. Big decrease in morning stiffness and swollen joints as well as Ritchie articular index with some improvement in fatigue scores. Minocycline did not inhibit progression of the disease however. Kloppenburg, Arthritis & Rheumatism ’94;37:629-36. One study with just 250 mg tetracycline QD did not find benefit.

Tetracyclines Helpful: AAAS 2001 meeting reported tetracyclines decrease periodontitis and cancer. Golub of SUNY Stony Brook found DM fosters breakdown of collagen, the structural protein in bone and connective tissue via colleganases. Tetracyclines protect collagen even in animals without periodontal germs by disarming collagenase although other antibiotics didn’t work. Was effective well below killing dose. Slows osteoporosis. Tetracyclines help periodontal disease in DM. Decreases cytokines e.g. interleukin-1 beta inflammatory compound which also decr insulin’s action. Use in treating AODM. Prevented cataracts, wasting, and impaired wound healing in animals with DM. Thwart angiogenesis. Helped Kaposi’s sarcoma with a 50% response rate in advanced cases and may help prostate CA. (Sci News 2/24/01) (Ed: Doxycycline, a long-acting tetracycline, helped me and is very inexpensive.)

Topical Anti-Inflammatories Inferior for Arthritis: Of 133 studies reviewed, 13 were considered of adequate scientific reliability representing 1983 patients. All were sponsored by pharmaceutical companies. All were stated as randomized controlled trials, but there were no details on method of randomization. Topical NSAIDs were superior to placebo in relieving pain due to osteoarthritis only in the first two weeks of treatment. No benefit was observed over placebo in weeks 3 and 4. A similar pattern was observed for function, stiffness, and clinical response rate ratio and number needed to treat. Topical NSAIDs were inferior to oral NSAIDs in the first week of treatment and associated with more local side effects such as rash, itch, or burning. Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials. Jinying Lin, Weiya Zhang, Adrian Jones, Michael Doherty, University of Nottingham, BMJ  8/7/2004;329:324. Ed: I strongly favor glucosamine and chondroitin over NSAIDs for arthritis with other alternatives as back-ups. 

Selenium Helped: In a DB PC study of RA patients with half given 200 microg/d of selenium and with both groups getting fish oil, researchers found decreased tenderness and inflammation with compatible lab changes in measures of inflammation. Heinle, Munchen, Med Klin 9/97;15:92 Suppl 3

Therapeutic Tape Helped Knee Osteoarthritis: In an 87-patient randomized single blind trial of therapeutic tape, control tape, or no tape for three weeks' duration and three week follow up for knee osteoarthritis, therapeutic tape caused a greater reduction in pain on all primary outcomes than either of the other two groups. A significant association was evident between intervention and change in pain at three weeks (P=0.000), with 73% (21/29) of the therapeutic tape group reporting improvement compared with 49% (14/29) of the control tape group and 10% (3/29) of the no tape group. Significantly greater improvement in pain and disability was observed on most secondary outcomes in the therapeutic tape group compared with the no tape group. Benefits of therapeutic tape were maintained three weeks after stopping treatment. Efficacy of knee tape in the management of osteoarthritis of the knee: blinded randomised controlled trial. Hinman RS, Crossley KM, et al. University of Melbourne. BMJ. 2003 Jul 19;327(7407):135

Tramadol-LP Minimal Benefit with Addiction and Side-Effects: In a short 14-day DB PC industry-funded study of 230 adults with chronic hip or knee osteoarthritis using tramadol LP 200 mg, a new once-daily, sustained-release formulation, pain was somewhat reduced in the tramadol LP group compared with the placebo group on day 7 (P = 0.002) and day 14 (P = 0.010), although the benefit was getting less with the passing of time. Patient assessment found 77% of the tramadol LP group reporting improvement by day 14, vs. 60% of the placebo group; One or more adverse event was reported by 45% of the tramadol LP group, compared with 19% of the placebo group (P < 0.001)(nausea, 22%; vomiting, 17% and somnolence, 12%). Efficacy and tolerability of sustained-release tramadolin the treatment of symptomatic osteoarthritis of the hip or knee: A multicenter, randomized, double-blind, placebo-controlled study. Malonne H, Coffiner M, et al. Universite Libre de Bruxelles, Belgium. Clin Ther. 2004 Nov;26(11):1774-82. Ed: Generic tramadol costs $47/month. What a rip. The new long acting variety will cost still more and patients won't be able to substitute.  The idea of using highly addictive opiates for a chronic illness is insane.  In this study, tramadol made a very small difference at two weeks and the difference was fading away. The individuals must not have had too much pain, since placebo helped 60%. Opiates don't slow disease progression like glucosamine and chondroitin do.  They just turn the arthritis victim into a drug addict as well.  Arthritis is a chronic condition, not a 14-day bout of pain.  In this irresponsible study motivated by greed, six people had to be put on a highly addictive medication for one person to experience any short-term benefit.

Uric Acid Increased by Meat; Reduced by Dairy: Using data from 14,809 adults in the Third National Health and Nutrition Examination Survey and adjusting for age, sex, total energy intake, body mass index, use of diuretics, beta-blockers, allopurinol, and uricosuric agents, self-reported hypertension and gout, serum creatinine level, and intake of alcohol, researchers found that the serum uric acid level increased with increasing total meat or seafood intake and decreased with increasing dairy intake. After adjusting for age, the differences in uric acid levels between the extreme quintiles of intake were 0.48 mg/dl for total meat, 0.16 mg/dl for seafood, and -0.21 mg/dl for total dairy intake. After adjusting for other covariates, the differences between the extreme quintiles were attenuated but remained significant (P < 0.05). The total protein intake was not associated with the serum uric acid level in multivariate analyses (P = 0.74 for trend). Milk 1 or more times per day had a lower serum uric acid level than did those who did not drink milk (multivariate difference -0.25; P < 0.001). Yogurt at least once every other day had a multivariate difference -0.26; P < 0.001. Intake of purine-rich foods, protein, and dairy products and relationship to serum levels of uric acid: the Third National Health and Nutrition Examination Survey. Choi HK, Liu S, Curhan G. MGH-Harvard. Arthritis Rheum. 2005 Jan;52(1):283-9.

Uric Acid: Colchicine Good Prophylaxis When Starting Allopurinol for Gout: In a DB PC study of 43 patients starting allopurinol for crystal-proven chronic gouty arthritis, those also given colchicine 0.6 mg po bid had fewer total flares (0.52 vs 2.91, p = 0.008) and less severe flares (3.64 vs 5.08, p = 0.018). Colchicine was well tolerated. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. Borstad GC, Bryant LR, et al. Lackland AFB, San Antonio. J Rheumatol. 2004 Dec;31(12):2429-32.

Vegan Diet Helps Arthritis: J Altern Complement Med 2002 Feb;8(1):71-5. In a single-blind study of 24 moderate-severe RA patients, 4 weeks on a low fat vegan found improvement in all measures of arthritis except morning stiffness. There was some modest decrease in the sed rate, and the RH factor.

Vegan Diet without Gluten Helps RA Arthritis: Orv Hetil 2001 Nov 18;142(46):2581-5, Karolinska Inst, Sweden. In a study of 66 patients who were randomly assigned, 40% showed clear improvement on a vegan diet vs. 4% on a healthy control diet after 1 year. IgG against gliadin and beta-lactoglobulin both decreased in vegan group. No x-ray changes were noted in vegan patients.

Vegan Diet Helps Sacroileitis: A 33-year-old woman with refractory HLA-27 B positive sacroileitis found relief in three days, went back to meat at 6 weeks and relapsed and again became totally symptom free back on a vegan diet. Forsch Komplementarmed Klass Naturheilkd 2001 Aug;8(4):228; Researchers emphasize avoiding milk products as well as meats.  Boneless animals such as shrimp, oysters, and lobsters are fine.  Shark, which has cartilage but no bone, may also be OK.  While fish oil helps arthritis, it is less clear whether actual fish is as safe.

Vegetarian Low Arachidonic Plus Fish Oil Best for Rheumatoid Arthritis: In a DB crossover study of 68 RA patient using 8 months of each diet with a two month washout, the vegetarians did best.  Arachidonic acid is found almost exclusively in meat (Especially in mammal fats and egg yolks, but not peanuts). Humans can manufacture from linoleic acid. In Low Arachidonic Acid patients (<90 mg/d), as compared to Western Diet patients, fish oil led to a significant reduction in the numbers of tender (28% vs. 11%) and swollen (34% vs. 22%) joints ( P<0.01). Compared to baseline levels, higher enrichment of eicosapentaenoic acid in erythrocyte lipids (244% vs. 217%) and lower formation of leukotriene B(4) (34% vs. 8%, P>0.01), 11-dehydro-thromboxane B(2) (15% vs. 10%, P<0.05), and prostaglandin metabolites (21% vs. 16%, P<0.003) were found in low arachidonic acid patients, especially when fish oil was given. Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Adam O, Beringer C, et al. Rheumatol Int 2003 Jan;23(1):27-36; Munich

Vitamin D Intake Associated with Lower Rates of Rheumatoid Arthritis: In an 11 year follow-up of 29,300 Iowa women ages 55-69, where 158 developed rheumatoid arthritis, those with higher intakes of vitamin D in food or by supplements were less likely to develop rheumatoid arthritis. Risk ratios were 0.72 and 0.66 for in food or via supplement. Univ Iowa, Linda Merlino, Arthritis Rheum. 2004:50:72-77. 

Vitamin D Genetic Variants Increase Osteo Risk: In a genetic study of individuals with and without osteoarthritis, VDR gene polymorphisms appeared to play a role in the etiology of symmetrical hand OA. Moreover, the association between the VDR gene and OA may be modified by calcium intake. Solovieva, et al. Helsinki. Arthr Res Ther 2005 Dec 30;8(1):R20.

Yogurt: Lactobacillus Rham GG Might Help Rheumatoid Arthritis: In a DB PC 12-month study of just 21 patients, those taking lactobacilli in capsules twice a day had a 71% decrease in tender and swollen joints (8.3 to 4.6) vs. 30% (5.5 to 4.8), however, there was no change in rheumatoid markers. Effects of probiotic therapy on the activity and activation of mild rheumatoid arthritis--a pilot study. Hatakka K, Martio J, Korpela M, Herranen M, Poussa T, Laasanen T, Saxelin M, Vapaatalo H, Moilanen E, Korpela R. Scand J Rheumatol. 2003;32(4):211-5. Ed: Regular yogurt would probably do just as good or better at lower cost in view of a couple studies comparing lactobacilli in capsules vs. yogurt for other conditions.

Zinc, Beta-Cryptoxanthin, Fruits, Cruciform Vegetables, Manganese, and Copper Help RA: In an 11-year follow-up Mayo study of 29,385 older women, supplemental zinc usage was associated with a 61% lower rate of rheumatoid arthritis (RR 0.39), fruit consumption 30% lower (RR 0.70), cruciform vegetable consumption 41% lower (RR 0.59), and vitamins C and E each 30% lower (RR 0.70); Manganese and copper supplements each had RRs = 0.50. There was no association with total carotenoids, alpha- or beta-carotene, lycopene, or lutein/zeaxanthin. Antioxidant micronutrients and risk of rheumatoid arthritis in a cohort of older women. Cerhan JR, Saag KG, Merlino LA, Mikuls TR, Criswell LA. Am J Epidemiol 2003 Feb 15;157(4):345-54, Am J Epidemiol 2003 Feb 15;157(4):345-54

Thomas E. Radecki, M.D., J.D.

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