There is no cure for<unk> , but treatments can improve symptoms and slow the progress of the disease. Disease-modifying treatment has the best results when it is started early and aggressively. The results of a recent systematic review found that combination therapy with tumor necrosis factor (TNF) and non-TNF biologics plus methotrexate (MTX) resulted in improved disease control, Disease Activity Score (DAS)-defined remission, and functional capacity compared with a single treatment of either methotrexate or a biologic alone. The goals of treatment are to minimize symptoms such as pain and swelling, to prevent bone deformity (for example, bone erosions visible in X-rays), and to maintain day-to-day functioning. This is primarily addressed with disease-modifying antirheumatic drugs (DMARDs); dosed physical activity; analgesics and physical therapy may be used to help manage pain.<unk>  should generally be treated with at least one specific anti-rheumatic medication. The use of benzodiazepines (such as diazepam) to treat the pain is not recommended as it does not appear to help and is associated with risks. Lifestyle Regular exercise is recommended as both safe and useful to maintain muscles strength and overall physical function. Physical activity is beneficial for people with<unk>  who experience fatigue, although there was little to no evidence to suggest that exercise may have an impact on physical function in the long term, a study found that carefully dosed exercise has shown significant improvements in patients with<unk> . Moderate effects have been found for aerobic exercises and resistance training on cardiovascular fitness and muscle strength in<unk> . Furthermore, physical activity had no detrimental side effects like increased disease activity in any exercise dimension. It is uncertain if eating or avoiding specific foods or other specific dietary measures help improve symptoms. Occupational therapy has a positive role to play in improving functional ability in people with<unk> . Weak evidence supports the use of wax baths (thermotherapy) to treat<unk>  in the hands. Educational approaches that inform people about tools and strategies available to help them cope with<unk>  may improve a person's psychological status and level of depression in the shorter-term. The use of extra-depth shoes and molded insoles may reduce pain during weight-bearing activities such as walking. Insoles may also prevent the progression of bunions. Disease modifying agents Disease-modifying antirheumatic drugs (DMARDs) are the primary treatment for<unk> . They are a diverse collection of drugs, grouped by use and convention. They have been found to improve symptoms, decrease joint damage, and improve overall functional abilities. DMARDs should be started early in the disease as they result in disease remission in approximately half of people and improved outcomes overall. The following drugs are considered as DMARDs: methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, TNF-alpha inhibitors (certolizumab, adalimumab, infliximab and etanercept), abatacept, and anakinra. Rituximab and tocilizumab are monoclonal antibodies and are also DMARDs. Use of tocilizumab is associated with a risk of increased cholesterol levels. Hydroxychloroquine, apart from its low toxicity profile, is considered effective in the moderate<unk>  treatment. The most commonly used agent is methotrexate with other frequently used agents including sulfasalazine and leflunomide. Leflunomide is effective when used from 6–12 months, with similar effectiveness to methotrexate when used for 2 years. Sulfasalazine also appears to be most effective in the short-term treatment of<unk> . Sodium aurothiomalate (gold) and cyclosporin are less commonly used due to more common adverse effects. However, cyclosporin was found to be effective in the progressive<unk>  when used up to one year. Agents may be used in combinations however, people may experience greater side effects. Methotrexate is the most important and useful DMARD and is usually the first treatment. A combined approach with methotrexate and biologics improves ACR50, HAQ scores and<unk>  remission<unk> tes. Triple therapy consisting of methotrexate, sulfasalazine and hydroxychloroquine may also effectively control disease activity. Adverse effects should be monitored regularly with toxicity including gastrointestinal, hematologic, pulmonary, and hepatic. Side effects such as nausea, vomiting or abdominal pain can be reduced by taking folic acid. A 2015 Cochrane review found rituximab with methotrexate to be effective in improving symptoms compared to methotrexate alone. Rituximab works by decreasing levels of B-cells (immune cell that is involved in inflammation). People taking rituximab had improved pain, function, reduced disease activity and reduced joint damage based on x-ray images. After 6 months, 21% more people had improvement in their symptoms using rituximab and methotrexate. Biological agents should generally only be used if methotrexate and other conventional agents are not effective after a trial of three months. They are associated with a higher<unk> te of serious infections as compared to other DMARDs. Biological DMARD agents used to treat<unk>  include: tumor necrosis factor alpha (TNFα) blockers such as infliximab; interleukin 1 blockers such as anakinra, monoclonal antibodies against B cells such as rituximab, interleukin 6 blockers such as tocilizumab, and T cell co-stimulation blockers such as abatacept. They are often used in combination with either methotrexate or leflunomide. Biologic monotherapy or tofacitinib with methotrexate may improve ACR50,<unk>  remission<unk> tes and function. Abatacept should not be used at the same time as other biologics. In those who are well controlled (low disease activity) on TNF blockers, decreasing the dose does not appear to affect overall function. Discontinuation of TNF blockers (as opposed to gradually lowering the dose) by people with low disease activity may lead to increased disease activity and may affect remission, damage that is visible on an x-ray, and a person's function. People should be screened for latent tuberculosis before starting any TNF blockers therapy to avoid reactivation of tuberculosis. TNF blockers and methotrexate appear to have similar effectiveness when used alone and better results are obtained when used together. Golimumab is effective when used with methotraxate. TNF blockers may have equivalent effectiveness with etanercept appearing to be the safest. Injecting etanercept, in addition to methotrexate twice a week may improve ACR50 and decrease<unk> diographic progression for up to 3 years. Abatacept appears effective for<unk>  with 20% more people improving with treatment than without but long term safety studies are yet unavailable. Adalimumab slows the time for the<unk> diographic progression when used for 52 weeks. However, there is a lack of evidence to distinguish between the biologics available for<unk> . Issues with the biologics include their high cost and association with infections including tuberculosis. Use of biological agents may reduce fatigue. The mechanism of how biologics reduce fatigue is unclear. Anti-inflammatory and analgesic agents Glucocorticoids can be used in the short term and at the lowest dose possible for flare-ups and while waiting for slow-onset drugs to take effect. Combination of glucocorticoids and conventional therapy has shown a decrease in<unk> te of erosion of bones. Steroids may be injected into affected joints during the initial period of<unk> , prior to the use of DMARDs or oral steroids. Non-NSAID drugs to relieve pain, like paracetamol may be used to help relieve the pain symptoms; they do not change the underlying disease. The use of paracetamol may be associated with the risk of developing ulcers. NSAIDs reduce both pain and stiffness in those with<unk>  but do not affect the underlying disease and appear to have no effect on people's long term disease course and thus are no longer first line agents. NSAIDs should be used with caution in those with gastrointestinal, cardiovascular, or kidney problems. Rofecoxib was withdrawn from the global market as its long-term use was associated to an increased risk of heart attacks and strokes. Use of methotrexate together with NSAIDs is safe, if adequate monitoring is done. COX-2 inhibitors, such as celecoxib, and NSAIDs are equally effective. A 2004 Cochrane review found that people preferred NSAIDs over paracetamol. However, it is yet to be clinically determined whether NSAIDs are more effective than paracetamol. The neuromodulator agents topical capsaicin may be reasonable to use in an attempt to reduce pain. Nefopam by mouth and cannabis are not recommended as of 2012 as the risks of use appear to be greater than the benefits. Limited evidence suggests the use of weak oral opioids but the adverse effects may outweigh the benefits. Alternatively, physical therapy has been tested and shown as an effective aid in reducing pain in patients with<unk> . As most<unk>  is detected early and treated aggressively, physical therapy plays more of a preventative and compensatory role, aiding in pain management alongside regular rheumatic therapy. Surgery Especially for affected fingers, hands, and wrists, synovectomy may be needed to prevent pain or tendon rupture when drug treatment has failed. Severely affected joints may require joint replacement surgery, such as knee replacement. Postoperatively, physiotherapy is always necessary. There is insufficient evidence to support surgical treatment on<unk>  shoulders. Physiotherapy For people with<unk> , physiotherapy may be used together with medical management. This may include cold and heat application, electronic stimulation, and hydrotherapy. Although medications improve symptoms of<unk> , muscle function is not regained when disease activity is controlled. Physiotherapy promotes physical activity. In<unk> , physical activity like exercise in the appropriate dosage (frequency, intensity, time,
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