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rheumatoid arthritis (RA)

See diagnostic criteria for rheumatoid arthritis (RA), cervical spine involvement in rheumatoid arthritis (RA) & articular deformities of rheumatoid arthritis (RA). Etiology: 1) unknown 2) infectious agent suspected - urogenital infections & gastroenteritis within 2 years may be modestly protective (RR=0.7-0.8) [65] - cross-reactivity between RA-relevant autoantigens & intestinal bacteria in the closely related families Lachnospiraceae & Ruminococcaceae - bacteria of the genus Subdoligranulum in the family Ruminococcaceae implicated specifically implicated in the pathology of RA [128] - Prevotella copri also implicated in the pathology of RA [128] 3) paraneoplastic syndrome (common in the elderly) [7] 4) smoking is a risk factor for rheumatoid arthritis [3] - smoking cessation might blunt risk for developing RA [119] 5) occupational exposure may play a role [104] - electrical & electronics workers, bricklayers & concrete workers, material handling operators (RR > 2) [104] - occupational inhalation of synthetic fiber dust to fungicides, insecticides, asbestos, silica dust (RR > 2) [130] - volatile organic chemicals - gasoline engine exhaust, welding fumes, organic solvents, carbon monoxide (RR > 1.5) [130] - automobile mechanics 6) increased risk in first year after 1st pregnancy [3] 7) consumption of ultraprocessed foods associated with increased risk of rheumtoid arthritis (RR~1.17) [138] Epidemiology: 1) occurs in 1% of adults 2) overall, women affected 3 fold more than men a) 6 fold in the 4th decade of life b) female:male ratio declines to 1:1 after 6th decade of life 3) age of onset peaks in 5th decade for both sexes 4) pleuro-pulmonary involvement is more common in men 5) seronegative rheumatoid arthritis more likely in men [3] 6) among women with rheumatoid arthritis, 2/3 will improve during pregnancy [3] Pathology: (see pathology of rheumatoid arthritis) Genetics: (60% of risk, see genetics of rheumatoid arthritis) Clinical manifestations: 1) time course of disease a) onset generally insidious b) course generally progressive, but may be exacerbations & remissions c) patients generally present with pain & swelling in > 3 small joints of the hands &/or feet & morning stiffness [3] d) symptoms present for > 6 weeks 2) musculoskeletal manifestations a) symmetric polyarthritis [3] - initially involves small joints of the hands, wrist & feet - wrist, MCP joint, PIP joint, MTP joint [3] - DIP joints generally spared [88] - progresses proximally to involve larger joints - not all symmetric arthritis is RA - involvement of a single joint is unusual for presentation or a flare of RA [3] b) joint pain & tenderness, local warmth [3] c) joint swelling: fusiform-shaped swelling of PIP joint d) palpable joint effusion [3] e) decreased range of motion - pain on active & passive range of motion [3] f) morning stiffness - lasts more than 1 hour - improves with activity g) manifestations of joint destruction/deformities - subluxations - joint dislocations - ankylosis d) joint contractures - ulnar deviation h) joints usually involved in RA - proximal interphalangeal (PIP) joint - metacarpophalangeal (MCP) joint - metatarsophalageal (MTP) joint - wrist i) joints commonly involved in RA - ankle - knee - elbow - cervical spine (50% of seropositive patients) - high posterior neck pain (50%) - occipital headaches - cervical spine instability [3]; C1, C2 subluxation j) joints not commonly involved - hip - shoulder - temporomandibular joint (TMJ) k) joints generally not involved - distal interphalangeal (DIP) joint - thoracic spine - lumbar spine l) periarticular manifestations [3] - popliteal (Baker's) cyst, ganglion cyst - tenosynovitis, tendonitis & bursitis - olecronon bursitis common - rotator cuff tendonitis common - tenosynovitis may cause trigger finger - swan neck deformity, boutonniere deformity - flexion contractures - periarticular osteopenia m) subcutaneous rheumatoid nodules over bony prominences or extensor surfaces [80] (images) n) carpal tunnel syndrome may be presenting symptom [3,36] 3) constitutional symptoms a) malaise b) easy fatigability c) muscle weakness d) anorexia e) weight loss f) low-grade fever 4) extra-articular manifestations a) pulmonary - obstructive airway disease - bronchiolitis obliterans (34%) - cough, fever, pulmonary infiltrates - bronchiectasis 14% [123] - pleural effusion - exudative, pleurisy 10%, rheumatoid pleuritis - lymphocytic predominance - low pleural fluid glucose - spindle-shaped cells (macrophages) - pulmonary rheumatoid nodules, pleural based - multiple basilar pulmonary nodules (Caplan's syndrome) - occur with active disease - bronchopleural fistula is a complication - interstitial lung disease (especially in smokers) 16% [126] - pulmonary interstitial fibrosis - interstitial pneumonia - acute lung injury - pulmonary hypertension due to pulmonary vasculitis - arytenoid arthritis - upper airway obstruction (rare) - hoarseness from cricoarytenoid joint involvement - increased risk for pulmonary infections [3] b) cardiovascular - pericarditis (50% of RA autopsies) - generally serous & asymptomatic - pericardial effusion (30-40%) - recurrent serous pericarditis may evolve into constrictive pericarditis (70% 1 year mortality if untreated) - coronary artery disease (independent risk factor) - valvular heart disease: leaflet fibrosis (30%) - cardiomyopathy, LV diastolic dysfunction (15%) c) vasculitis (mediated by immune complex deposition) [80] - rheumatoid nodules [80] (images) - palpable purpura - pyoderma gangrenosum, ulcerations - polyarteritis with mononeuritis multiplex - nailfold infarcts [80] - systemic vasculitis is rare d) neurological manifestations - entrapment neuropathies - especially carpal tunnel syndrome - mononeuritis multiplex - foot drop or wrist drop (vasculitis) - myelopathy from cervical vertebral subluxation - occipital headache from C1-C2 subluxation - arm paresthesia, hyperreflexia - increased risk of intubation e) diffuse muscular atrophy - drug-induced myopathy: steroid myopathy [3] f) bone: periarticular osteopenia, osteoporosis, increased risk of fractures g) ocular manifestations: - xerophthalmia [3] - scleritis may progress to scleromalacia perforans & blindness - episcleritis, keratitis - keratoconjunctivitis sicca (Sjogren's syndrome) h) skin: - rheumatoid nodules over extensor surfaces & juxta-articular regions, almost exclusively in patients with rheumatoid factor positive RA - rheumatoid nodule commonly over olecranon [3] - periungual purpura is a result of nailfold thrombosis i) Felty's syndrome - splenomegaly, leukopenia - cutaneous ulcers in lower extremities [3] - large granular lymphocyte syndrome j) xerostomia [3] k) secondary amyloidosis: cardiac amyloidosis, renal amyloidosis l) anemia of chronic inflammation [3] m) seronegative RA is not associated with extra-articular manifestations* * ref [3] states seronegative RA identical to seropositive RA Laboratory: 1) serology [68] a) rheumatoid factor 1] single most useful laboratory test 2] positive in 80% of RA patients, sensitivity 70%, specificity 85% - often negative in early phases of disease - seronegative RA may convert to seropositive RA [3] 3] false positives occur a] other systemic diseases b] 1% of normal population, especially women 4] not useful for assessing disease activity [3] b) antinuclear antibodies (ANA) 1] high titers in 30% of RA patients 2] generally diffuse immunofluorescence pattern c) anti-cyclic citrullinated peptide antibody (anti-CCP)* - sensitivity 70%, specificity 95% [3] d) anti keratin antibodies (AKA) e) anti perinuclear factor f) anti RA33 g) anti RA-associated nuclear antigen (RANA) h) anti synovial stimulatory protein p205 i) anti-GOLGB1 2) synovial fluid analysis a) WBC 2000-50,000/mm3 b) 40-75% neutrophils 3) pleural fluid analysis (pleural effusion, pleuritis) a) mixed inflammatory cells (exudative) b) low pleural fluid glucose (< 30 mg/dL) 4) erythrocyte sedimentation rate (ESR) or serum CRP (C-reactive protein in serum) a) non-specific b) generally elevated c) may be helpful in following course of disease 5) protein electrophoresis - polyclonal gammopathy 6) anemia workup a) complete blood count (CBC) 1] normocytic normochromic anemia 2] leukocytosis 3] may be granulocytopenia with Felty's syndrome 4] thrombocytosis 5] pancytopenia may occur with Felty's syndrome b) peripheral smear - large granular lymphocyte syndrome (Felty's syndrome) c) iron studies: - low serum iron with transferrin saturation (serum iron/TIBC) > 15%, consistent with anemia of chronic disease 7) liver function tests may be mildly abnormal, especially serum alkaline phosphatase a) may be related to treatment b) may be due to nodular hyperplasia of the liver 8) serum chemistries recommended for baseline workup [3] a) serum creatinine b) serum electrolytes c) serum 25-hydroxyvitamin D - patients on glucocorticoids 9) urinalysis recommended for baseline workup [3] 10) stool guaiac for occult blood [3] 11) genetic testing - PTPN22 gene mutation 12) Vectra DA panel 12 different unspecified biomarkers of unknown clinical significance 13) troponin I in serum predicts excess cardiovascular mortality [107] 14) see ARUP consult [29] * most specific diagnostic laboratory test Special laboratory: - cardiac stress test if - epigastric pain &/or LUQ abdominal pain - nausea, vomiting, diaphoresis - normal abdominal CT - long-term glucocorticoids [133] - even if - normal electrocardiogram - 2 sets of cardiac enzyme levels 6 hours apart are normal - upper GI endoscopy unlikely to be helpful if - normal abdominal examination - normal abdominal CT [133] - pulmonary function testing - especially in patients with kyphosis [14] Radiology: 1) radiographs of joints (hand & wrists &/or feet)* 1) periarticular soft tissue swelling 2) juxta-articular osteoporosis (osteopenia) 3) juxta-articular bony erosions 4) symmetric narrowing of joint space 5) subluxations [3] 6) ankylosis [88] 7) involvement of the metacarpophalangeal joints & proximal interphalageal joints 8) radiographs of hands may show no deformities or erosions in early RA [133] 9) useful for initial diagnosis & for monitoring disease progression [3] - radiographic changes even in the absence of symptoms suggest a need to change treatment [3] 10) routine X-rays of hands & feet in suspected RA of extremely low yield [137] 2) radiograph of cervical spine a) C1,C2 most commonly involved b) erosive disease in 20% c) lateral views in flexion & extension d) preoperative cervical spine films in flexion & extension - cervical spine vulnerable during endotracheal intubation [95] 3) MRI of the cervical spine to assess spinal cord compression 4) MRI & ultrasound are more sensitive imaging modalities for synovitis & early erosive rheumatoid arthritis than radiography [40] - ultrasound not useful in guiding treatment [86] 5) MRI is not indicated for routine monitoring of disease activity - asymptomatic individuals frequently with abnormalities on MRI [3,91,117] (see arthritis Radiology section) 6) bone-density (DEXA) for patients on glucocorticoids - bone mineral density may underestimate risk of fracture [3] * radiograph images [120] Differential diagnosis: 1) osteoarthritis 2) spondyloarthropathies a) ankylosing spondylitis b) psoriatic arthritis (psoriasis or pitted nails) c) Reiter's syndrome d) colitic arthritis 3) systemic lupus erythematosus (SLE) (skin rash & leukopenia) 4) systemic sclerosis (Raynaud's phenomenon) 5) Lyme disease 6) crystal-induced arthritis a) gout b) pseudogout 7) paraneoplastic syndrome (especially in the elderly) [7] 8) parvovirus B19 infection (daycare worker or mother of small children) - symmetric polyarthritis present for > 6 weeks suggests RA 9) hemochromatosis (2nd MCP & PIP joints) 10) polymyositis, dermatomyositis (proximal muscle weakness) 11) post-rubella immunization arthritis [3] Complications: 1) Felty's syndrome (splenomegaly, granulocytopenia) 2) amyloidosis occurs rarely a) generally AA amyloidosis (amyloid protein AA) b) manifested by proteinuria +/- nephrotic syndrome, +/- hematuria c) treatment unsatisfactory; prognosis is poor 3) osteoporosis, increased risk of fracture [16] - vertebral compression fractures (kyphosis) 4) spinal cord compression due to cervical spine disease - C1, C2 subluxation - 50% mortality in 1 year without surgery 5) mortality a) greatest 3-10 years after diagnosis b) correlates with disease severity factors, older age, radiologic progression, RF titer, anti-CCP, resistance to therapy & extra-articular manifestations [3] c) biologic agents may be protective relative to conventional DMARDs from sepsis or mortality following serious infection [89] 6) increased risk of cardiovascular disease [22,64] a) major cause of death in RA [3] - smoking doubles this risk [105] b) coronary artery disease c) increased risk of atrial fibrillation (HR=1.3) [27] d) increased risk of stroke (HR=3.0 in patients < 50) [27] e) pericardial effusion (30-40%) f) valvular heart disease - leaflet fibrosis (< 30%) - increased risk of aortic stenosis [135] g) heart failure, left ventricular diastolic dysfunction [3] - subclinical myocardial inflammation correlates with RA disease activity [118] - TNF inhibitor toxicity h) coronary artery calcification scoring is more likely than cardiovascular risk calculators to place RA patients in a high-risk category [66] - the implications are unknown i) patients with severe extra-articular manifestations of RA at highest risk for cardiovascular events [3] 7) increased risk of thromboembolism [31] (RR=2) 8) pulmonary complications - drug-related lung disease (methotrexate) - bronchiolitis - interstitial pneumonia, organizing pneumonia - rheumatoid nodules - pulmonary embolism 8) muscle atrophy due to disuse & glucocorticoid myopathy, especially interosseous muscles & quadriceps [3] 10) risk of cancer similar for DMARDs vs biologic agents [99] 11) infectious arthritis (acute monoarthritis) - synovial fluid cultures, blood cultures if signs of systemic infection - empiric antibiotics awaiting cultures [131,132] 12) increased risk of Parkinson's disease (RR=1.74) [134] 13) anemia of chronic inflammation Management: - general a) physical therapy - hand therapy cost-effective [60] b) occupational therapy c) cardiovascular risk reduction - moderate-vigorous exercise reduce fatigue as well as cardiovascular risk [140] d) early, agrressive therapy with multiple agents [32] e) treat to target of remission or low disease activity [3] - reduces joint damage & cardiovascular risk, & increases productivity === pharmacologic agents === 1) disease-modifying anti-rheumatic drugs (DMARDs) a) methotrexate, start with 7.5 mg PO weekly 1] improves long-term survival [10,12] by reducing cardiac deaths 2] adjunctive prednisone 10 mg QD for 1st 2 years may be of benefit [28] - taper & discontinue prednisone after 2 years [28] 3] probably best initial DMARD [3] - relatively low cost, good efficacy, generally well-tolerated, good long-term compliance 4] gold-standard DMARD for treatment of RA [3] 5] monotherapy for initial treatment of rapidly progressive or erosive RA [3,56] 6] in combination with sulfasalazine & hydroxychloroquine [18,32,55] 7] subcutaneous methotrexate is more effective than once-weekly oral dosing [98] & should be tried before resorting to a biologic agent 8] maximize use of methotrexate prior to resorting to other agents [125] 9] contraindicated in pregnancy [3] b) hydroxychloroquine, start with 400 mg PO QD - used to treat early, mild & non-erosive disease & in combination with methotrexate & sulfasalazine [3] - safe during pregnancy [3] c) sulfasalazine, start with 500 mg PO QD - safe during pregnancy [3] d) leflunomide (Arava) may be alternative to methotrexate e) cyclophosphamide (Cytoxan) f) azathioprine (Imuran) g) penicillamine h) dapsone i) minocycline or doxycycline 100 mg PO BID [4] 1] within the 1st year of diagnosis 2] may delay use of steroids or other DMARDs 3] allow at least 3 months for therapeutic effect j) use of multiple DMARDs concurrently may be more effective than a single agent at a cost of increased adverse effects k) starting DMARD within 3 months of diagnosis may be the new standard of care [3,9] 2) initial therapy with multiple DMARDs [18] a) methotrexate, sulfasalazine & hydroxychloroquine is standard (triple therapy) [32] & may be more durable than treatment with biologics [100] b) methotrexate, sulfasalazine, prednisone 60 mg QD, tapered to 7.5 mg QD over 7 weeks c) methotrexate plus TNF-alpha inhibitor - more effective than triple therapy [124] d) recommended as initial therapy for early aggressive rheumatoid arthritis [55] - ref [56] challenges this recommendation, noting that methotrexate alone is effective in 30% of these patients with no cost to coverting to multiple DMARDs at 6 months for methotrexate monotherapy failure [56] e) DMARDs in combination result in non-inferior outcomes to treatment with TNF inhibitors at substantially lower costs [67] f) 73% of patients on triple therapy vs 63% of those on methotrexate/etanercept remain on treatment at 1 year [100] g) more patients change from methotrexate/etanercept to triple therapy than from triple therapy to methotrexate/etanercept [100] 3) prednisone or prednisolone in addition to DMARDs or biologics a) intra-articular injection for acutely inflamed joints b) low-dose oral therapy (prednisone 10 mg QD) [8] - prednisolone 7.5 mg QD [19] may retard progression of RA - 5 mg of prednisolone PO QD confers moderate benefit [127] - does not increase cardiovascular risk [136] - risk of serious infection is 14%/year vs 9%/year without prednisone [122] c) long-term use of prednisone-equivalent dose 10 mg QD, cumulative dose > 1800 mg associated with increased risk of adverse effects (RR=1.2) [106] d) <= 5 mg prednisone/day considered safe for long-term use [101] - absence of RA flares without adrenal insufficiency in 77% of patients continuing prednisone 5 mg/day vs 65% of patients tapering prednisone [121] - risk of serious infection is 11%/year vs 9%/year without prednisone [122] e) screen for & treat osteoporosis - calcium, vitamin D, bisphosphonate f) glucocorticoids do not alter course of disease 4) biologic agents a) TNF-alpha inhibitors (all of similar benefit) [3] 1] etanercept (Enbrel) 25 mg SC twice weekly [13] a] may be superior to methotrexate b] in combination with methotrexate superior to either alone [15,32] c] after 36 weeks of stable disease, cutting the dose of etanercept by 1/2 results in minimal loss of effectiveness [33] d] stopping etanercept results in disease flares in 57% of patients [33] e] patients who achieve remission with etanercept plus methotrexate a] 23% & 40% of patients are able to complete taper of etanercept with or without methotrextate [61] b] remission sustained after taper [61] c] study funded by Pfizer f] addition of etanercept to methotrexate 25 mg/week (50 mg/week max dose) preferred over maximizing dose of methotrexate [3] g] patients who fail treatment with a TNF-alpha inhibitor are more likely to respond to another biologic agent that is not a TNF-alpha inhibitor than another TNF-alpha inhibitor (69% vs 52%) [90] h] TNF-alpha inhibitors diminish cardiovascular risk by controlling disease activity & presumably inflammation [93] 2] infliximab (Remicade) in combination with methotrexate [26] 3] adalimumab (Humira)* in combination with methotrexate [57] 4] certolizumab 5] golimumab 6] TNF-alpha inhibitor + methotrexate is the most effective treatment of rheumatoid arthritis [3] 7] standard practice is to add TNF-alpha inhibitor to methotrexate [83] 8] rheumatoid arthritis more likely to flair when patients in remission stappe TNF-alpha inhibitor (51 vs 18%) [87] b) anakinra (Kineret) 1-2 mg/kg SC [11] in combination with methotrexate c) Janus kinase inhibitors - at least as effective or more effective [139] than TNF-alpha inhibitors - tofacitinib - in combination with methotrexate for TNF inhibitor failure: effective in 40% of patients [34] - monotherapy with tofacitinib is superior to methotrexate monotherapy at the cost of increased adverse effects [59] - initial therapy with tocilizumab +/- methotrexate increases likelihood of rapid remission vs methotrexate alone (84-86% vs 44%) [84] - initial treatment with methotrexate with addition of tocilizumab after 2 years results in similar outcomes as initiating therapy with tocilizumab [84] d) rituximab (Rituxan) FDA approved 2005 - as effective as a TNF-inhibitor & more cost-effective [83] - standard practice is to add rituximab to methotrexate [83] e) abatacept (Orencia) FDA approved 2005 f) combination therapy with two biologic agents (TNF inhibitor, anakinra, rituximab, abatacept) is contraindicated [3,55] g) after symptom control is achieved, biologic agent can be discontinued in some patients [57] h) infection risks highest with infliximab, etanercept, & rituximab [81] i) adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab & abatacept, all in combination with methotrexate, are recommended as options for treating rheumatoid arthritis, only if: - disease is severe, disease activity score (DAS28) > 5.1 & - disease has not responded to intensive therapy with a combination of conventional DMARDs (NICE) [NGC] j) sarilumab (IL-6 receptor inhibitor) superior as monotherapy to adalimumab (TNF-alpha inhibitor) [92] k) upadacitinib (Rinvoq) a JAK-1 inhibitor with benefits of > 1 year duration for treatment of refractory RA [103] l) screening for tuberculosis prior to intitiating biologic & periodically during therapy [3] 5) statin in combination with DMARDs [16] 6) intensive therapy may improve outcome (see TICORA study) [16] 7) methotrexate, sulfasalazine & hydroxychloroquine as effective as etanercept for patients with methotrexate failure [35] & more cost-effective [97] 8) patients more likely to comply with methotrexate+biologic agent than with methotrexate, sulfasalazine & hydroxychloroquine [96] 9) non-steroidal anti-inflammatory agents (NSAIDs) - symptomatic relief but do not alter course of disease [3] 10) Tripterygium wilfordii Hook F may be of benefit === surgery & other procedures === 1) all patients with RA undergoing general anesthesia should have cervical spine X-rays to assess atlantoaxial subluxation - identify RA-related cervical spine disease prior to elective surgery (risk of spinal cord injury during intubation & extubation) [3,39] - cervical spine radiography with flexion & extension views 2) indications for surgery: a) incapacitating pain & disability due to joint damage or tendon rupture b) nerve entrapment syndromes unresponsive to local injection, rest & casting c) septic joint unresponsive to needle drainage & antibiotics d) cervical spinal cord compression 3) surgical procedures a) synovectomy, bursectomy, bunionectomy, nodulectomy b) joint fusion & joint replacement c) arthroplasty (hip & knee) d) tendon repairs & transfers 4) electrotherapy, thermotherapy 5) vagus nerve stimulation - reduces proinflammatory cytokine production - diminishes disease severity [85] === other considerations === 1) activity a) aerobic exercise b) adequate rest 2) diet, nutrition - fish oils may augment DMARD therapy [62] - eating fish at least twice a week is associated with lower disease activity [102] - calcium & vitamin D for all patients [3] 3) patient education - smoking associated with 2-fold increase in mortality [105] 4) prevention: - long-term, moderate alcohol consumption associated with diminished risk for rheumatoid arthritis (RR=0.5) [30] - smoking is a risk factor; smoking cessation reduces risk [3,44] - bisphosphates for osteoporosis 5) vaccination - routine immunizations including Covid-19 vaccine, annual influenza vaccine, pneumococal vaccine - treatment may influence immunogenicity of vaccines - methotrexate discontinuation for 2 weeks after influenza vaccination improves immunogenicity of the vaccine without increasing RA disease activity [108] 6) adjuvant physical therapy & occupational therapy [3] 7) prognosis - increasing longevity in rheumatoid arthritis patients, possibly because of earlier & more fequent use of biologic agents & conventional DMARDs [94] 8) complications: - acute monoarthritis: - empiric antibiotics for infectious arthritis awaiting cultures [131,132] * Veteran's Administration VISN 21 preferred agent in this class

Interactions

disease interactions

Related

anti-rheumatoid arthritis-associated antigen (RANA) articular manifestations/deformities of rheumatoid arthritis (RA) cervical spine involvement in rheumatoid arthritis (RA) diagnostic criteria for rheumatoid arthritis (RA) extra-articular manifestations of rheumatoid arthritis genetics of rheumatoid arthritis pathology of rheumatoid arthritis rheumatoid factor (RF) rheumatoid lung disease rheumatoid nodule rheumatologic disorders in pregnancy

Useful

disease-modifying antirheumatic agent (DMARD)

Specific

adult-onset Still's disease Felty's syndrome juvenile rheumatoid arthritis; juvenile idiopathic arthritis; Still's disease rheumatoid arthritis in the elderly

General

arthritis autoimmune disease connective tissue disease; soft tissue disease

Database Correlations

OMIM 180300

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 776-778
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 821-828, 786-87
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Prescriber's Letter 6(10):58, Oct, 1999 (subscription needed) http://www.prescribersletter.com
  5. Journal Watch vol 19, #24, pg 192-93 Dec 15, 1999 Kong YY et al Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 402:304, 1999 PMID: 10580503
  6. Journal Watch 21(2):1, 2001 Bathon JM et al A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 343:1586,2001 PMID: 11096165 - Lipsky PE et al Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med 343:1594, 2000 PMID: 11096166 Kipple JH Biologic therapy for rheumatoid arthritis. N Engl J Med 343:1640, 2000 PMID: 11096174
  7. Weiner, S in: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  8. Journal Watch 22(4):27, 2002 van Everdingen AA et al Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med 136:1-12, 2002 PMID: 11777359
  9. Prescriber's Letter 9(3):13 2002 (subscription needed) http://www.prescribersletter.com
  10. Prescriber's Letter 9(5):26 2002 (subscription needed) http://www.prescribersletter.com
  11. Journal Watch 22(9):70, 2002 Dayer J-M & Bresniban R Targeting interleukin-1 in the treatment of rheumatoid arthritis. Arthritis Rheum 46:574, 2002 PMID: 11920390
  12. Journal Watch 22(10):76, 2002 Choid HK et al Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 359:1173, 2002 PMID: 11955534
  13. Journal Watch 22(15):116, 2002 Genovese MC et al Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum 46:1443, 2002 PMID: 12115173
  14. Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004 - Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  15. Journal Watch 24(7):58, 2004 Klareskog L et al Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 363:675, 2004 PMID: 15001324
  16. Journal Watch 24(15):119, 2004 McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, Ford I, Capell HA, Sattar N. Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet. 2004 Jun 19;363(9426):2015-21. PMID: 15207950
  17. Journal Watch 24(17):137, 2004 Journal Watch 24(17):137-38, 2004 Grigor C, Capell H, Stirling A, McMahon AD, Lock P, Vallance R, Kincaid W, Porter D. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004 Jul 17;364(9430):263-9. PMID: 15262104
  18. Goekoop-Ruiterman YPM et al, Clinical and radiographic outcomes of four different strategies in patients with early rheumatoid arthritis (the BeSt study): A randomized, controlled trial. Arthritis Rheum 2005; 52:3381 PMID: 16258899 - Weisman MH Progress toward the cure of rheumatoid arthritis? The BeSt study. Arthritis Rheum 2005; 52:3326 PMID: 16258928
  19. Wassenber S et al, Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over 2 years: A multicenter, double- blind, placebo-controlled trial. Arthritis Rheum 2005; 52:3371 PMID: 16255011 - Svensson B et al Low-dose prednisolone in addition to the initial disease- modifiying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: A two-year randomized trial. Arthritis Rheum 2005; 52:3360 PMID: 16255010
  20. Turesson C & Matteson EL, Genetics of rheumatoid arthritis Mayo Clin Proc 2006; 81:94 PMID: 16438485
  21. Breedveld FC et al, The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum 2006, 54:26 PMID: 16385520
  22. Roman MJ et al, Preclinical carotid atherosclerosis in patients with rheumatoid arthritis. Ann Intern Med 2006; 144:249 PMID: 16490910
  23. Jacobs JW et al, Followup radiographic data on patients with rheumatoid arthritis who participated in a two-year trial of prednisone therapy of placebo. Arthritis Rheum 2006; 54:1422 PMID: 16645970
  24. Choosing Medications for Adults With Rheumatoid Arthritis Clinician Summary Guide published 9 Apr 2008 Agency for Healthcare Research and Quality (AHRQ) http://effectivehealthcare.ahrq.gov/healthInfo.cfm?infotype=sg&DocID=85&ProcessID=14
  25. Prescriber's Letter 16(2): 2008 PATIENT HANDOUT: What I Need to Know About My Rheumatoid Arthritis Medication COMMENTARY: Rheumatoid Arthritis: The Role of DMARDs Detail-Document#: 250210 (subscription needed) http://www.prescribersletter.com - GUIDELINES: Use of Disease-Modifying Antirheumatic Drugs (DMARDs) in Rheumatoid Arthritis http://www.rheumatology.org/publications/guidelines/recommendations.pdf
  26. van Vollenhoven RF et al Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial. Lancet 2009 Aug 8; 374:459. PMID: 19665644
  27. Lindhardsen J et al Risk of atrial fibrillation and stroke in rheumatoid arthritis: Danish nationwide cohort study BMJ 2012;344:e1257 PMID: 22403267 http://www.bmj.com/content/344/bmj.e1257
  28. Journal Watch, Massachusetts Medical Society, March 22, 2012 Bakker MF et al. Low-dose prednisone inclusion in a methotrexate-based, tight control strategy for early rheumatoid arthritis: A randomized trial. Ann Intern Med 2012 Mar 6; 156:329. PMID: 22393128
  29. ARUP Consult: Rheumatoid Arthritis - RA The Physician's Guide to Laboratory Test Selection & Interpretation https://arupconsult.com/content/rheumatoid-arthritis
  30. Di Giuseppe D et al Long term alcohol intake and risk of rheumatoid arthritis in women: a population based cohort study BMJ 2012;345:e4230 PMID: 22782847 http://www.bmj.com/content/345/bmj.e4230
  31. Holmqvist ME et al Risk of Venous Thromboembolism in Patients With Rheumatoid Arthritis and Association With Disease Duration and Hospitalization JAMA. 2012;308(13):1350-1356 PMID: 23032551 http://jama.jamanetwork.com/article.aspx?articleid=1367509
  32. Moreland LW et al. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: The Treatment of Early Aggressive Rheumatoid Arthritis trial. Arthritis Rheum 2012 Sep; 64:2824 PMID: 22508468
  33. Smolen JS et al. Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): A randomised controlled trial. Lancet 2013 Jan 17 PMID: 23294500 - Miossec P. Rheumatoid arthritis: Still a chronic disease. Lancet 2013 Jan 17 PMID: 23294499
  34. Burmester GR et al. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: A randomised phase 3 trial. Lancet 2013 Feb 9; 381:451. PMID: 23294500 - Miossec P. Kinase inhibition in rheumatoid arthritis: A big advance? Lancet 2013 Feb 9; 381:429. PMID: 23294499
  35. O'Dell JR et al Therapies for Active Rheumatoid Arthritis after Methotrexate Failure. N Engl J Med. June 11, 2013 PMID: 23755969 http://www.nejm.org/doi/full/10.1056/NEJMoa1303006 - Bathon JM and McMahon DJ Making Rational Treatment Decisions in Rheumatoid Arthritis When Methotrexate Fails. N Engl J Med. June 11, 2013 PMID: 23755970 http://www.nejm.org/doi/full/10.1056/NEJMe1306381
  36. Muramatsu K, Tanaka H, Taguchi T. Peripheral neuropathies of the forearm and hand in rheumatoid arthritis: diagnosis and options for treatment. Rheumatol Int. 2008 Aug;28(10):951-7 PMID: 18528693
  37. Whiting PF, Smidt N, Sterne JA et al Systematic review: accuracy of anti-citrullinated Peptide antibodies for diagnosing rheumatoid arthritis. Ann Intern Med. 2010 Apr 6;152(7):456-64; W155-66 PMID: 20368651
  38. Saag KG, Teng GG, Patkar NM et al American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008 Jun 15;59(6):762-84. PMID: 18512708
  39. Grauer JN, Tingstad EM, Rand N, Christie MJ, Hilibrand AS. Predictors of paralysis in the rheumatoid cervical spine in patients undergoing total joint arthroplasty. J Bone Joint Surg Am. 2004 Jul;86-A(7):1420-4. PMID: 15252088
  40. Ostergaard M, Pedersen SJ, Dohn UM. Imaging in rheumatoid arthritis--status and recent advances for magnetic resonance imaging, ultrasonography, computed tomography and conventional radiography. Best Pract Res Clin Rheumatol. 2008 Dec;22(6):1019-44 PMID: 19041075
  41. Huizinga TW, Pincus T. In the clinic. Rheumatoid arthritis. Ann Intern Med. 2010 Jul 6;153(1):ITC1-1-ITC1-15 PMID: 20621898
  42. Aletaha D, Neogi T, Silman AJ, Funovits J et al 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010 Sep;62(9):2569-81 PMID: 20872595
  43. Visser K, Katchamart W, Loza E et al Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann Rheum Dis. 2009 Jul;68(7):1086-93 PMID: 19033291
  44. Costenbader KH, Feskanich D, Mandl LA, Karlson EW. Smoking intensity, duration, and cessation, and the risk of rheumatoid arthritis in women. Am J Med. 2006 Jun;119(6):503.e1-9. PMID: 16750964
  45. Hyrich KL, Deighton C, Watson KD et al Benefit of anti-TNF therapy in rheumatoid arthritis patients with moderate disease activity. Rheumatology (Oxford). 2009 Oct;48(10):1323-7 PMID: 19706737
  46. Jones G, Sebba A, Gu J et al Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis. 2010 Jan;69(1):88-96 PMID: 19297346
  47. Cooper GS. Occupational exposures and risk of rheumatoid arthritis: continued advances and opportunities for research. J Rheumatol. 2008 Jun;35(6):950-2. PMID: 18528947
  48. Finckh A, Bansback N, Marra CA et al Treatment of very early rheumatoid arthritis with symptomatic therapy, disease-modifying antirheumatic drugs, or biologic agents: a cost-effectiveness analysis. Ann Intern Med. 2009 Nov 3;151(9):612-21 PMID: 19884622
  49. Gaujoux-Viala C, Smolen JS, Landewe R et al Current evidence for the management of rheumatoid arthritis with synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2010 Jun;69(6):1004-9 PMID: 20447954
  50. Hetland ML, Christensen IJ, Tarp U et al Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: results from eight years of surveillance of clinical practice in the nationwide Danish DANBIO registry. Arthritis Rheum. 2010 Jan;62(1):22-32 PMID: 20039405
  51. Klareskog L, Catrina AI, Paget S. Rheumatoid arthritis. Lancet. 2009 Feb 21;373(9664):659-72 PMID: 19157532
  52. Markatseli TE, Papagoras C, Drosos AA. Prognostic factors for erosive rheumatoid arthritis. Clin Exp Rheumatol. 2010 Jan-Feb;28(1):114-23. PMID: 20346251
  53. Singh JA, Beg S, Lopez-Olivo MA. Tocilizumab for rheumatoid arthritis. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD008331 PMID: 20614469
  54. Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis: a systematic review. J Rheumatol. 2010 Jun;37(6):1096-104 PMID: 20436075
  55. Singh JA, Furst DE, Bharat A 2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res, 64: 625-629 PMID: 22473917 http://onlinelibrary.wiley.com/doi/10.1002/acr.21641/abstract
  56. O'Dell JR et al. Validation of the methotrexate-first strategy in patients with early, poor-prognosis rheumatoid arthritis: Results from a two-year, randomized, double-blind trial. Arthritis Rheum 2013 Aug; 65:1985 PMID: 23686414
  57. Smolen JS et al. Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: The randomised controlled OPTIMA trial. Lancet 2013 Oct 26 PMID: 24168956 - Kirwan JR and Boers M. Biological treatment in rheumatoid arthritis: When to stop? Lancet 2013 Oct 26 PMID: 24168959
  58. Narvaez JA, Narvaez J, Serrallonga M Cervical spine involvement in rheumatoid arthritis: correlation between neurological manifestations and magnetic resonance imaging findings. Rheumatology (Oxford). 2008 Dec;47(12):1814-9. PMID: 18927193
  59. Lee EB et al. Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med 2014 Jun 19; 370:2377 PMID: 24941177
  60. Lamb SE et al. Exercises to improve function of the rheumatoid hand (SARAH): A randomised controlled trial. Lancet 2014 Oct 10; PMID: 25308290 - Opava CH and Bjork M. Towards evidence-based hand exercises in rheumatoid arthritis. Lancet 2014 Oct 10; PMID: 25308291
  61. Emery P et al. Sustained remission with etanercept tapering in early rheumatoid arthritis. N Engl J Med 2014 Nov 6; 371:1781 PMID: 25372086 http://www.nejm.org/doi/full/10.1056/NEJMoa1316133
  62. Proudman SM et al. Fish oil in recent onset rheumatoid arthritis: A randomised, double-blind controlled trial with algorithm-based drug use. Ann Rheum Dis 2015 Jan; 74:89 PMID: 24081439 http://ard.bmj.com/content/74/1/89
  63. O'Dell JR. Therapeutic strategies for rheumatoid arthritis. N Engl J Med 2004 Jun 18; 350:2591. PMID: 15201416
  64. Ogdie A et al. Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: A population- based cohort study. Ann Rheum Dis 2015 Feb; 74:326. PMID: 25351522 http://ard.bmj.com/content/74/2/326
  65. Sandberg MEC et al. Recent infections are associated with decreased risk of rheumatoid arthritis: A population-based case-control study. Ann Rheum Dis 2015 Feb 5; PMID: 25656683 http://ard.bmj.com/content/early/2015/01/16/annrheumdis-2014-206493
  66. Kawai VK et al. The ability of the 2013 American College of Cardiology/American Heart Association cardiovascular risk score to identify rheumatoid arthritis patients with high coronary artery calcification scores. Arthritis Rheum (Munch) 2015 Feb; 67:381 PMID: 25371313 http://onlinelibrary.wiley.com/doi/10.1002/art.38944/abstract;jsessionid=381EF68A8007FE817BF108CAF0861E84.f01t02
  67. Scott DL et al. Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial. BMJ 2015 Mar 13; 350:h1046 PMID: 25769495
  68. Pincus T, Sokka T. Laboratory tests to assess patients with rheumatoid arthritis: advantages and limitations. Rheum Dis Clin North Am. 2009 Nov;35(4):731-4 PMID: 19962617
  69. Anderson J, Caplan L, Yazdany J et al Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res (Hoboken). 2012 May;64(5):640-7 PMID: 22473918
  70. Cameron M, Gagnier JJ, Chrubasik S. Herbal therapy for treating rheumatoid arthritis. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD002948 PMID: 21328257
  71. Jacobs JW Optimal use of non-biologic therapy in the treatment of rheumatoid arthritis. Rheumatology (Oxford). 2012 Jun;51 Suppl 4:iv3-8 PMID: 22513146
  72. Pavelka K, Kavanaugh AF, Rubbert-Roth A, Ferraccioli G. Optimizing outcomes in rheumatoid arthritis patients with inadequate responses to disease-modifying anti-rheumatic drugs. Rheumatology (Oxford). 2012 Jul;51 Suppl 5:v12-21 PMID: 22718922
  73. Pisetsky DS, Ward MM. Advances in the treatment of inflammatory arthritis. Best Pract Res Clin Rheumatol. 2012 Apr;26(2):251-61 PMID: 22794097
  74. Radner H, Neogi T, Smolen JS, Aletaha D. Performance of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: a systematic literature review. Ann Rheum Dis. 2014 Jan;73(1):114-23 PMID: 23592710
  75. Sen D, Brasington R. Tight disease control in early RA. Rheum Dis Clin North Am. 2012 May;38(2):327-43 PMID: 22819087
  76. Vermeer M, Kuper HH, Bernelot Moens HJ et al Adherence to a treat-to-target strategy in early rheumatoid arthritis: results of the DREAM remission induction cohort. Arthritis Res Ther. 2012 Nov 23;14(6):R254 PMID: 23176083
  77. Vermeer M, Kuper HH, Moens HJ et al Sustained beneficial effects of a protocolized treat-to-target strategy in very early rheumatoid arthritis: three-year results of the Dutch Rheumatoid Arthritis Monitoring remission induction cohort. Arthritis Care Res (Hoboken). 2013 Aug;65(8):1219-26 PMID: 23436821
  78. Yarilina A, Xu K, Chan C, Ivashkiv LB. Regulation of inflammatory responses in tumor necrosis factor- activated and rheumatoid arthritis synovial macrophages by JAK inhibitors. Arthritis Rheum. 2012 Dec;64(12):3856-66 PMID: 22941906
  79. Dhawan SS, Quyyumi AA. Rheumatoid arthritis and cardiovascular disease. Curr Atheroscler Rep. 2008 Apr;10(2):128-33. PMID: 18417067
  80. DermNet NZ. Rheumatoid arthritis (images) http://dermnetnz.org/immune/rheumatoid.html
  81. Yun H, Xie F, Delzell E et al Comparative Risk of Hospitalized Infection Associated With Biologic Agents in Rheumatoid Arthritis Patients Enrolled in Medicare. Arthritis Rheumatol. 2016 Jan;68(1):56-66. PMID: 26315675
  82. Pieringer H, Stuby U, Biesenbach G. Patients with rheumatoid arthritis undergoing surgery: how should we deal with antirheumatic treatment? Semin Arthritis Rheum. 2007 Apr;36(5):278-86. Review. PMID: 17204310
  83. Coblyn JS Head-to-Head Comparison of Rituximab vs. TNF Inhibitors for Rheumatoid Arthritis. NEJM Journal Watch. June 21, 2016 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - Porter D, van Melckebeke J, Dale J et al. Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis who require biological treatment (ORBIT): An open-label, randomised controlled, non-inferiority, trial. Lancet. 2016 May 16. PMID: 27197690
  84. Bijlsma JWJ et al. Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): A multicentre, randomised, double-blind, double-dummy, strategy trial. Lancet 2016 Jun 7; PMID: 27287832 - Scott DL. Beyond methotrexate monotherapy for early rheumatoid arthritis. Lancet 2016 Jun 7 PMID: 27287831
  85. Koopman FA et al. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci U S A 2016 Jul 5 PMID: 27382171 Free Article
  86. Haavardsholm EA et al. Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial. BMJ 2016 Aug 26; 354:i4205 PMID: 27530741 Free PMC Article
  87. Ghiti Moghadam M, Vonkeman HE, Ten Klooster PM et al. Stopping tumor necrosis factor inhibitor treatment in patients with established rheumatoid arthritis in remission or with stable low disease activity: A pragmatic multicenter, open- label randomized controlled trial. Arthritis Rheumatol 2016 Aug; 68:1810 PMID: 26866428 http://onlinelibrary.wiley.com/doi/10.1002/art.39626/abstract
  88. Seetharaman M (slide show with images) Rheumatoid Arthritis: In and Out of the Joint. Medscape. March 22, 2016 http://reference.medscape.com/features/slideshow/rheumatoid-arthritis
  89. Richter A, Listing J, Schneider M et al. Impact of treatment with biologic DMARDs on the risk of sepsis or mortality after serious infection in patients with rheumatoid arthritis. Ann Rheum Dis 2016 Sep; 75:1667 PMID: 26567181 Free PMC Article http://ard.bmj.com/content/75/9/1667
  90. Gottenberg JE, Brocq O, Perdriger A et al. Non-TNF-targeted biologic vs a second anti-TNF drug to treat rheumatoid arthritis in patients with insufficient response to a first anti-TNF drug: A randomized clinical trial. JAMA 2016 Sep 20; 316:1172 PMID: 27654603
  91. Mangnus L et al. Magnetic resonance imaging-detected features of inflammation and erosions in symptom-free persons from the general population. Arthritis Rheumatol 2016 Nov; 68:2593 PMID: 27213695
  92. Burmester GR, Lin Y, Patel R et al Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. Nov 17, 2016 PMID: 27856432 Free full text http://ard.bmj.com/content/early/2016/11/16/annrheumdis-2016-210310.abstract
  93. Ljung L, Rantapaa-Dahlqvist S, Jacobsson LT, Askling J.. Response to biological treatment and subsequent risk of coronary events in rheumatoid arthritis. Ann Rheum Dis 2016 Dec; 75:2087 PMID: 26984007
  94. Zhang Y, Lu N, Peloquin C et al. Improved survival in rheumatoid arthritis: A general population- based cohort study. Ann Rheum Dis 2017 Feb; 76:408 PMID: 27338777 Free PMC Article http://ard.bmj.com/content/76/2/408
  95. NEJM Knowledge+. Question of the Week. March, 2017 http://knowledgeplus.nejm.org/question-of-week/707/ - Lourie H, Stewart WA Spontaneous Atlantoaxial Dislocation - A Complication of Rheumatoid Disease. N Engl J Med 1961; 265:677-681October 5, 1961 http://www.nejm.org/doi/full/10.1056/NEJM196110052651405 - Neva MH, Hakkinen A, Makinen H et al High prevalence of asymptomatic cervical spine subluxation in patients with rheumatoid arthritis waiting for orthopaedic surgery. Ann Rheum Dis. 2006 Jul;65(7):884-8. Epub 2005 Nov 3. PMID: 16269427 PMCID: PMC1798218 Free PMC Article - Manczak M, Gasik R. Cervical spine instability in the course of rheumatoid arthritis - imaging methods. Reumatologia. 2017;55(4):201-207. PMID: 29056776 PMCID: PMC5647537 Free PMC article. Review.
  96. Sauer BC, Teng CC, Tang D et al. Persistence with conventional triple therapy versus a tumor necrosis factor inhibitor and methotrexate in US veterans with rheumatoid arthritis. Arthritis Care Res (Hoboken) 2017 Mar; 69:313 PMID: 27273801 http://onlinelibrary.wiley.com/doi/10.1002/acr.22944/abstract
  97. Bansback N, Phibbs CS, Sun H et al Triple Therapy Versus Biologic Therapy for Active Rheumatoid Arthritis: A Cost-Effectiveness Analysis. Ann Intern Med. 2017. May 30 PMID: 28554192 http://annals.org/aim/article/2629469/triple-therapy-versus-biologic-therapy-active-rheumatoid-arthritis-cost-effectiveness - Losina E, Katz JN Improvement at Any Cost? The Art and Science of Choosing Treatment Strategies for Rheumatoid Arthritis. Ann Intern Med. 2017. May 30 PMID: 28554193 http://annals.org/aim/article/2629472/improvement-any-cost-art-science-choosing-treatment-strategies-rheumatoid-arthritis
  98. Rohr MK, Mikuls TR, Cohen SB, Thorne JC, O'Dell JR. Underuse of methotrexate in the treatment of rheumatoid arthritis: A national analysis of prescribing practices in the US. Arthritis Care Res (Hoboken) 2017 Jun; 69:794. PMID: 27863180
  99. Wadstrom H, Frisell T, Askling J et al. Malignant neoplasms in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors, tocilizumab, abatacept, or rituximab in clinical practice: A nationwide cohort study from Sweden. JAMA Intern Med 2017 Sep 18 PMID: 28975211
  100. Peper SM, Lew R, Mikuls T et al. Rheumatoid arthritis treatment after methotrexate: The durability of triple therapy versus etanercept. Arthritis Care Res (Hoboken) 2017 Oct; 69:1467. PMID: 28388820 http://onlinelibrary.wiley.com/doi/10.1002/acr.23255/abstract
  101. Roubille C, Rincheval N, Dougados M et al. Seven-year tolerability profile of glucocorticoids use in early rheumatoid arthritis: Data from the ESPOIR cohort. Ann Rheum Dis 2017 Nov; 76:1797 PMID: 28213564 http://ard.bmj.com/content/76/11/1797
  102. Kelly JC Eating Fish May Reduce Rheumatoid Arthritis Symptoms Medscape - Jun 23, 2017. https://www.medscape.com/viewarticle/882026 - Tedeschi SK, Bathon JM, Giles JT et al The relationship between fish consumption and disease activity in rheumatoid arthritis. Arthritis Care Res (Hoboken). 2018 Mar;70(3):327-332. PMID: 28635117 http://onlinelibrary.wiley.com/doi/10.1002/acr.23295/abstract
  103. McNamara D JAK-1 Inhibitor Effective for RA, but Safety Signal Troubles. Medscape - Nov 13, 2017. https://www.medscape.com/viewarticle/888522 - Walsh N Rinvoq for RA: Benefits Persist Beyond 1 Year - Manufacturer's extension study shows no loss of clinical response. MedPage Today November 6, 2020 https://www.medpagetoday.com/meetingcoverage/acr/89523 - van Vollenhoven R, et al Upadacitinib monotherapy in methotrexate-naive patients with rheumatoid arthritis: results at 72 weeks. American College of Rheumatology (ACR) 2020; Abstract 0207
  104. Pullen LC Occupational Exposures Increase Rheumatoid Arthritis Risk. Medscape - Aug 10, 2017. https://www.medscape.com/viewarticle/884103 - Ilar A, Alfredsson L, Wiebert P, Klareskog L, Bengtsson C. Occupation and Risk of Developing Rheumatoid Arthritis: Results From a Population-Based Case-Control Study. Arthritis Care Res (Hoboken). 2017 Aug 10. PMID: 28795508
  105. Sparks JA, Chang SC, Nguyen UDT et al. Smoking behavior changes in the early rheumatoid arthritis period and risk of mortality during thirty-six years of prospective followup. Arthritis Care Res (Hoboken) 2018 Jan; 70:19. PMID: 28464477 http://onlinelibrary.wiley.com/doi/10.1002/acr.23269/abstract
  106. Best JH, Kong AM, Lenhart GM et al. Association between glucocorticoid exposure and healthcare expenditures for potential glucocorticoid-related adverse events in patients with rheumatoid arthritis. J Rheumatol 2018 Mar; 45:320. PMID: 29335343 http://www.jrheum.org/content/45/3/320
  107. Walsh N. Troponin Predicts Mortality in Inflammatory Arthritis. High levels associated with all-cause and cardiovascular death. MedPage Today. May 01, 2018 https://www.medpagetoday.com/meetingcoverage/bsr/72632 - Skeoch S, et al The association of high sensitivity troponin levels with subsequent cardiovascular mortality in an inflammatory arthritis cohort: Results from the Norfolk arthritis register. British Society for Rheumatology (BSR) 2018; Abstract O10.
  108. Park JK, Lee YJ, Shin K et al. Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: A randomised clinical trial. Ann Rheum Dis 2018 Jun; 77:898 PMID: 29572291 Free PMC Article
  109. National Institute of Arthritis and Muscluloskeletal and Skin Diseases (NIAMS) Rheumatoid Arthritis https://www.niams.nih.gov/health-topics/rheumatoid-arthritis
  110. Crowson CS, Liao KP, Davis JM 3rd Rheumatoid arthritis and cardiovascular disease. Am Heart J. 2013 Oct;166(4):622-628.e1. Review. PMID: 24093840 Free PMC Article
  111. Di Giuseppe D, Orsini N, Alfredsson L, Askling J, Wolk A. Cigarette smoking and smoking cessation in relation to risk of rheumatoid arthritis in women. Arthritis Res Ther. 2013 Apr 22;15(2):R56. PMID: 23607815 Free PMC Article
  112. Artifoni M, Rothschild PR, Brezin A et al Ocular inflammatory diseases associated with rheumatoid arthritis. Nat Rev Rheumatol. 2014 Feb;10(2):108-16. Review. PMID: 24323074
  113. Chang PY, Yang CT, Cheng CH, Yu KH. Diagnostic performance of anti-cyclic citrullinated peptide and rheumatoid factor in patients with rheumatoid arthritis. Int J Rheum Dis. 2016 Sep;19(9):880-6. PMID: 25940989
  114. Ince-Askan H, Dolhain RJ. Pregnancy and rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2015 Aug-Dec;29(4-5):580-96. Review. PMID: 26697768
  115. Del Grande M, Del Grande F, Carrino J et al Cervical spine involvement early in the course of rheumatoid arthritis. Semin Arthritis Rheum. 2014 Jun;43(6):738-44. Review. PMID: 24444595
  116. Singh JA, Saag KG, Bridges SL Jr et al 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016 Jan;68(1):1-26. Review. PMID: 26545940 Free Article
  117. Moller-Bisgaard S, Horslev-Petersen K, Ejbjerg B et al. Effect of magnetic resonance imaging vs conventional treat-to-target strategies on disease activity remission and radiographic progression in rheumatoid arthritis: The IMAGINE-RA randomized clinical trial. JAMA 2019 Feb 5; 321:461. PMID: 30721294 https://jamanetwork.com/journals/jama/fullarticle/2724024 - Aletaha D, Smolen JS. Achieving clinical remission for patients with rheumatoid arthritis. JAMA 2019 Feb 5; 321:457. PMID: 30721278 https://jamanetwork.com/journals/jama/fullarticle/2724006
  118. Amigues I, Tugcu A, Russo C et al. Myocardial inflammation, measured using 18-fluorodeoxyglucose positron emission tomography with computed tomography, is associated with disease activity in rheumatoid arthritis. Arthritis Rheumatol 2019 Apr; 71:496. PMID: 30407745 https://onlinelibrary.wiley.com/doi/abs/10.1002/art.40771
  119. Liu X, Tedeschi SK, Barbhaiya M et al. Impact and timing of smoking cessation on reducing risk of rheumatoid arthritis among women in the Nurses' Health Studies. Arthritis Care Res (Hoboken) 2019 Jul; 71:914. PMID: 30790475 https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.23837
  120. Satis H, Tufan A. Images in Clinical Medicine. Telescoping Fingers in Rheumatoid Arthritis. N Engl J Med 2019; 381:e41. Dec 12, PMID: 31826343 https://www.nejm.org/doi/full/10.1056/NEJMicm1905982
  121. Burmester GR et al. Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): A double-blind, multicentre, randomised controlled trial. Lancet 2020 Jul 25; 396:267 PMID: 32711802 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30636-X/fulltext
  122. George MD, Baker JF, Winthrop K et al Risk for Serious Infection With Low-Dose Glucocorticoids in Patients With Rheumatoid Arthritis. A Cohort Study. Ann Intern Med. Sept 22, 2020 PMID: 32956604 https://www.acpjournals.org/doi/10.7326/M20-1594 - Orange DE, Mehta B. Rethinking the Balance of Risks and Rewards of Chronic Low-Dose Glucocorticoids in Rheumatoid Arthritis. Ann Intern Med. Sept 22, 2020 PMID: 32956596 https://www.acpjournals.org/doi/10.7326/M20-6010
  123. Huang S et al. Rheumatoid arthritis-related lung disease detected on clinical chest computed tomography imaging: Prevalence, risk factors, and impact on mortality. Semin Arthritis Rheum 2020 Dec; 50:1216 PMID: 33059295 https://www.sciencedirect.com/science/article/abs/pii/S0049017220302596
  124. Curtis JR, Palmer JL, Reed GW Real-World Outcomes Associated with Triple Therapy versus TNFi/MTX Therapy. Arthritis Care Res (Hoboken). 2020 May 6 PMID: 32374918
  125. Walsh N New ACR Rheumatoid Arthritis Guideline: Emphasis on Methotrexate. Many RA patients succeed with optimized use of the DMARD before adding another medication. https://www.medpagetoday.com/rheumatology/arthritis/93323 - Fraenkel L, Bathon JM, England BR et al 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res 2021 Jul;73(7):924-939. Online June 8. PMID: 34101387 https://onlinelibrary.wiley.com/doi/10.1002/acr.24596
  126. Zamora-Legoff JA, Krause ML, Crowson CS et al. Progressive decline of lung function in rheumatoid arthritis-associated interstitial lung disease. Arthritis Rheumatol. 2017;69(3):542-549 PMID: 27788297 PMCID: PMC5328843 Free PMC article https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.39971
  127. Boers M, Hartman L, Opris-Belinski D et al. Low dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+: The pragmatic randomised, double-blind placebo-controlled GLORIA trial. Ann Rheum Dis 2022 Jul; 81:925 PMID: 35641125 PMCID: PMC9209692 Free PMC article https://ard.bmj.com/content/81/7/925
  128. Gever J Momentum Builds for Microbiome as RA Trigger. Second study published in a week's time to implicate intestinal bacteria in joint pathology. MedPage Today October 26, 2022 https://www.medpagetoday.com/rheumatology/arthritis/101435 - Chriswell ME Lefferts AR, Clay MR et al Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain of Subdoligranulum. Science Translational Medicine. 2022. 14(688):eabn5166. Oct 26 PMID: 36288282 https://www.science.org/doi/10.1126/scitranslmed.abn5166
  129. Gever J Does Rheumatoid Arthritis Get Its Start in the Gut? Patients and at-risk individuals show antibodies to common intestinal bacterium. MedPage Today October 20, 2022 https://www.medpagetoday.com/rheumatology/arthritis/101321 - Seifert JA, Bemis EA, Ramsden K et al Association of antibodies to Prevotella copri in anti-CCP-positive individuals at-risk for developing rheumatoid arthritis and in those with early or established rheumatoid arthritis. Arthritis & Rheumatology. 2022. Oct 19 PMID: 36259174 https://onlinelibrary.wiley.com/doi/abs/10.1002/art.42370
  130. Gever J Not Just a Miner's Problem: Workplace Fumes, Dust Tied to RA. Swedish study expands range of airborne toxics associated with rheumatic disease. MedPage Today December 6, 2022 https://www.medpagetoday.com/rheumatology/arthritis/102083 - Tang B, Liu Q, Ilar A et al Occupational inhalable agents constitute major risk factors for rheumatoid arthritis, particularly in the context of genetic predisposition and smoking. Annals of Rheumatic Diseases. 2022. Dec 6 https://ard.bmj.com/content/early/2022/11/28/ard-2022-223134
  131. Galloway JB, Hyrich KL, Mercer LK et al Risk of septic arthritis in patients with rheumatoid arthritis and the effect of anti-TNF therapy: results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis. 2011 Oct;70(10):1810-4. PMID: 21784730 PMCID: PMC3168332 Free PMC article
  132. Edwards CJ, Cooper C, Fisher D, Field M, van Staa TP, Arden NK. The importance of the disease process and disease-modifying antirheumatic drug treatment in the development of septic arthritis in patients with rheumatoid arthritis. Arthritis Rheum. 2007 Oct 15;57(7):1151-7 PMID: 17907232 Free article.
  133. NEJM Knowledge+ Rheumatology - Fraenkel L, Bathon JM, England BR et al 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2021 Jul;73(7):1108-1123. PMID: 34101376
  134. Kang J, Eun Y, Jang W et al Rheumatoid Arthritis and Risk of Parkinson Disease in Korea. JAMA Neurol. Published online May 1, 2023. PMID: 37126341 https://jamanetwork.com/journals/jamaneurology/fullarticle/2804530
  135. Johnson TM, Mahabir CA, Yang Y et al Aortic Stenosis Risk in Rheumatoid Arthritis. JAMA Intern Med. Published online July 31, 2023 PMID: 37523173 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2807944
  136. So H, Lam TO, Meng H, Lam SHM, Tam LS. Time and dose-dependent effect of systemic glucocorticoids on major adverse cardiovascular event in patients with rheumatoid arthritis: a population-based study. Ann Rheum Dis. 2023 Nov;82(11):1387-1393. Epub 2023 Jul 24. PMID: 37487608
  137. Ulijn E, den Broeder N, Ten Cate D et al. Limited diagnostic and prognostic value of routine radiographs in newly presenting arthritis suspected of rheumatoid arthritis: A retrospective study. Arthritis Care Res (Hoboken) 2024 Apr; 76:497-502. PMID: 37933435 https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr.25271
  138. Zhoo H, Bai Y, Liu Y et al Association of ultra-processed food consumption with risk of rheumatoid arthritis: A retrospective cohort study in the UK Biobank. Am J Clin Nutr. 2024 Aug 18:S0002-9165(24)00674-9. PMID: 39163975 https://ajcn.nutrition.org/article/S0002-9165(24)00674-9/abstract
  139. Eberhard A, Di Giuseppe D, Askling J et al Effectiveness of janus kinase inhibitors compared with biologic disease modifying anti-rheumatic drugs on pain reduction in rheumatoid arthritis: Results from a nationwide Swedish cohort study. Arthritis Rheumatol. 2024 Sep 22. PMID: 39308007 https://acrjournals.onlinelibrary.wiley.com/doi/abs/10.1002/art.43014
  140. Gray SR, Montoye AHK, Vondrasek JD Associations of physical activity levels with fatigue in people with inflammatory rheumatic diseases in the LIFT trial. Rheumatol Adv Pract. 2024 Aug 24;8(3):rkae106. PMID: 39257857 PMCID: PMC11384110 Free PMC article.