Rituximab for rheumatoid arthritis.

BACKGROUND: Rituximab is a selective, B-cell depleting, biologic agent for treating refractory rheumatoid arthritis (RA). It is a chimeric monoclonal antibody targeted against CD 20 that is promoted as therapy for patients who fail to respond to other biologics. There is evidence to suggest that rituximab is effective and well tolerated when used in combination with methotrexate for RA. OBJECTIVES: To evaluate the benefits and harms of rituximab for the treatment of RA. SEARCH METHODS: We conducted a search (until January 2014) in electronic databases (The Cochrane Library, MEDLINE, EMBASE, CINAHL, Web of Science), clinical trials registries, and websites of regulatory agencies. Reference lists from comprehensive reviews were also screened. SELECTION CRITERIA: All controlled trials comparing treatment with rituximab as monotherapy or in combination with any disease modifying anti-rheumatic drug (DMARD) (traditional or biologic) versus placebo or other DMARD (traditional or biologic) in adult patients with active RA. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias and abstracted data from each study. MAIN RESULTS: We included eight studies with 2720 patients. For six studies selection bias could not be evaluated and two studies were considered to have low risk of bias. The level of evidence ranged from low to high, but was rated as moderate for most outcomes. We have prioritised reporting of rituximab (two 1000 mg doses) in combination with methotrexate since this is the approved dose and most commonly used combination. We also reported data on other combinations and doses as supplementary information in the results section of the review.American College of Rheumatology (ACR) 50 response rates were statistically significantly improved with rituximab (two 1000 mg doses) in combination with methotrexate compared with methotrexate alone at 24 to 104 weeks. The RR for achieving an ACR 50 at 24 weeks was 3.3 (95% CI 2.3 to 4.6); 29% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate achieved the ACR 50 compared to 9% of controls. The absolute treatment benefit (ATB) was 21% (95% CI 16% to 25%) with a number needed to treat (NNT) of 6 (95% CI 4 to 9).At 52 weeks, the RR for achieving clinical remission (Disease Activity Score (DAS) 28 joints < 2.6) with rituximab (two 1000 mg doses) in combination with methotrexate compared with methotrexate monotherapy was 2.4 (95% CI 1.7 to 3.5); 22% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate achieved clinical remission compared to 11% of controls. The ATB was 11% (95% CI 2% to 20%) with a NNT of 7 (95% CI 4 to 13).At 24 weeks, the RR for achieving a clinically meaningful improvement (CMI) in the Health Assessment Questionnaire (HAQ) (> 0.22) for patients receiving rituximab combined with methotrexate compared to patients on methotrexate alone was 1.6 (95% CI 1.2 to 2.1). The ATB was 24% (95% CI 12% to 36%) with an NNT of 5 (95% CI 3 to 13). At 104 weeks, the RR for achieving a CMI in HAQ (> 0.22) was 1.4 (95% CI 1.3 to 1.6). The ATB was 24% (95% CI 16% to 31%) with a NNT of 5 (95% CI 3 to 7).At 24 weeks, the RR for preventing radiographic progression in patients receiving rituximab (two 1000 mg doses) in combination with methotrexate was 1.2 (95% CI 1.0 to 1.4) compared to methotrexate alone; 70% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate had no radiographic progression compared to 59% of controls. The ATB was 11% (95% CI 2% to 19%) and the NNT was 10 (95% CI 5 to 57). Similar benefits were observed at 52 to 56 weeks and 104 weeks.Statistically significantly more patients achieved a CMI on the physical and mental components of the quality of life, measured by the Short Form (SF)-36, in the rituximab (two 1000 mg doses) in combination with methotrexate-treated group compared with methotrexate alone at 24 to 52 weeks (RR 2.0, 95% CI 1.1 to 3.4; NNT 4, 95% CI 3 to 8 and RR 1.4, 95% CI 1.1 to 1.9; NNT 8, 95% CI 5 to 19, respectively); 34 and 13 more patients out of 100 showed an improvement in the physical component of the quality of life measure compared to methotrexate alone (95% CI 5% to 84%; 95% CI 7% to 8%, respectively).There was no evidence of a statistically significant difference in the rates of withdrawals because of adverse events or for other reasons (that is, withdrawal of consent, violation, administrative, failure to return) in either group. However, statistically significantly more people receiving the control drug withdrew from the study compared to those receiving rituximab (two 1000 mg doses) in combination with methotrexate at all times (RR 0.40, 95% CI 0.32 to 0.50; RR 0.61, 95% CI 0.40 to 0.91; RR 0.48, 95% CI 0.28 to 0.82; RR 0.58, 95% CI 0.45 to 0.75, respectively). At 104 weeks, 37% withdrew from the control group and 20% withdrew from the rituximab (two 1000 mg doses) in combination with methotrexate group. The absolute risk difference (ARD) was -20% (95% CI -34% to -5%) with a number needed to harm (NNH) of 7 (95% CI 5 to 11).A greater proportion of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate developed adverse events after their first infusion compared to those receiving methotrexate monotherapy and placebo infusions (RR 1.6, 95% CI 1.3 to 1.9); 26% of those taking rituximab plus methotrexate reported more events associated with their first infusion compared to 16% of those on the control regimen with an ARD of 9% (95% CI 5% to 13%) and a NNH of 11 (95% CI 21 to 8). However, no statistically significant differences were noted in the rates of serious adverse events. AUTHORS' CONCLUSIONS: Evidence from eight studies suggests that rituximab (two 1000 mg doses) in combination with methotrexate is significantly more efficacious than methotrexate alone for improving the symptoms of RA and preventing disease progression.

Acupuncture in the treatment of rheumatic diseases.

Acupuncture has been used for millennia in traditional Chinese medicine as a technique believed to restore the balance of energy in the body caused by disease through the use of needles inserted into specific points or energy channels. This energy is called the de qi. The use of acupuncture for the treatment of pain in musculoskeletal disorders is increasing. Some patients seek alternative therapies because of lack of improvement with conventional treatments. The potential physiological effects of acupuncture on pain relief have been attributed to biochemical processes, such as the release of endorphins into the limbic structures, subcortical areas and brain stem, mechanisms that are also present in placebo-induced analgesia. In addition, pain relief with acupuncture is also associated with patient expectations, beliefs, and interactions with their acupuncturists. In this review, we summarize the latest evidence on the treatment of musculoskeletal conditions including rheumatoid arthritis, fibromyalgia, neck pain, shoulder pain, low back pain, and knee pain with traditional Chinese acupuncture (TCA), electroacupuncture (EA), and the use of moxibustion. Acupuncture is relatively safe, but there are still reports of serious and fatal side effects that must be taken into account when recommending this therapy. Many of the latest trials assessing the benefits of acupuncture in rheumatic diseases found that acupuncture was not better than sham acupuncture, implying that the analgesic effects observed are related to a strong placebo response. While the literature on this topic is extensive, many of the studies lack methodological rigor, and additional large, well-controlled, high quality trials are still needed to determine if acupuncture might be useful in the treatment of chronic rheumatic diseases.

Lipid paradox in rheumatoid arthritis: changes with rheumatoid arthritis therapies.

Rheumatoid arthritis (RA) is associated with increased cardiovascular (CV) morbidity and mortality, related not only to traditional CV risk factors, but also to a chronic inflammatory state. However, lipid profiles in RA are different from those observed in the general population at risk of CV disease, where there is evidence of a positive relationship between disease and high cholesterol levels. In untreated patients with active RA this relationship is different, with a paradoxical effect resulting in lower levels of cholesterol associated with an increased risk of CV disease. In this review, we summarize the latest evidence on lipid abnormalities in the setting of RA and the interaction between inflammation and lipoproteins, as well as the effect of DMARDs and biologic therapies on lipid profiles and the possible implications for CV outcomes in this population.