Editing Rheumatoid arthritis (section)

==Diagnosis==

===Imaging===
[[Image:RheumatoideArthritisAP.jpg|thumb|X-ray of the hand in rheumatoid arthritis]]
[[Image:Inflamatory arthritis2010.JPG|thumb|Appearance of synovial fluid from a joint with inflammatory arthritis]]
[[File:X-ray of right fourth PIP joint with bone erosions by rheumatoid arthritis.jpg|thumb|Closeup of [[bone erosion]]s in rheumatoid arthritis<ref>{{cite journal | vauthors = Ideguchi H, Ohno S, Hattori H, Senuma A, Ishigatsubo Y | title = Bone erosions in rheumatoid arthritis can be repaired through reduction in disease activity with conventional disease-modifying antirheumatic drugs | journal = Arthritis Research & Therapy | volume = 8 | issue = 3 | pages = R76 | year = 2006 | pmid = 16646983 | pmc = 1526642 | doi = 10.1186/ar1943 | doi-access = free }}</ref>]]
[[X-ray]]s of the hands and feet are generally performed when many joints are affected. In RA, there may be no changes in the early stages of the disease or the x-ray may show [[osteopenia]] near the joint, soft tissue swelling, and a smaller than normal joint space. As the disease advances, there may be bony erosions and subluxation. Other medical imaging techniques such as [[magnetic resonance imaging]] (MRI) and ultrasound are also used in RA.<ref name="McGraw Hill"/><ref>{{cite journal | vauthors = Takase-Minegishi K, Horita N, Kobayashi K, Yoshimi R, Kirino Y, Ohno S, Kaneko T, Nakajima H, Wakefield RJ, Emery P | title = Diagnostic test accuracy of ultrasound for synovitis in rheumatoid arthritis: systematic review and meta-analysis | journal = Rheumatology | volume = 57 | issue = 1 | pages = 49–58 | date = January 2018 | pmid = 28340066 | doi = 10.1093/rheumatology/kex036 | doi-access = free }}</ref>

Technical advances in ultrasonography like high-frequency transducers (10&nbsp;MHz or higher) have improved the spatial resolution of ultrasound images depicting 20% more erosions than conventional radiography. Color Doppler and power Doppler ultrasound are useful in assessing the degree of synovial inflammation as they can show vascular signals of active synovitis. This is important, since in the early stages of RA, the synovium is primarily affected, and synovitis seems to be the best predictive marker of future joint damage.<ref>{{cite journal |vauthors=Schueller-Weidekamm C |date=Apr 29, 2010 |title=Modern ultrasound methods yield stronger arthritis work-up |journal=Diagnostic Imaging |volume=32 |url=http://www.diagnosticimaging.com/ultrasound/modern-ultrasound-methods-yield-stronger-arthritis-work |access-date=October 21, 2018 |archive-date=April 9, 2019 |archive-url=https://web.archive.org/web/20190409091359/https://www.diagnosticimaging.com/ultrasound/modern-ultrasound-methods-yield-stronger-arthritis-work |url-status=dead }}</ref>

===Blood tests===
When RA is clinically suspected, a physician may test for [[rheumatoid factor]] (RF) and [[anti-citrullinated protein antibodies]] (ACPAs measured as anti-CCP antibodies).<ref>{{cite journal | vauthors = Westwood OM, Nelson PN, Hay FC | title = Rheumatoid factors: what's new? | journal = Rheumatology | volume = 45 | issue = 4 | pages = 379–385 | date = April 2006 | pmid = 16418203 | doi = 10.1093/rheumatology/kei228 | doi-access = free }}{{subscription required}}</ref>{{rp|382}}
The test is positive approximately two-thirds of the time, but a negative RF or CCP antibody does not rule out RA; rather, the arthritis is called ''[[seronegative]]'', which occurs in approximately a third of people with RA.<ref>{{cite journal | vauthors = Salman E, Çetiner S, Boral B, Kibar F, Erken E, Ersözlü ED, Badak SÖ, Bilici Salman R, Sertdemir Y, Çetin Duran A, Yaman A | title = Importance of 14-3-3eta, anti-CarP, and anti-Sa in the diagnosis of seronegative rheumatoid arthritis | journal = Turkish Journal of Medical Sciences | volume = 49 | issue = 5 | pages = 1498–1502 | date = October 2019 | pmid = 31651120 | pmc = 7018368 | doi = 10.3906/sag-1812-137 }}</ref> During the first year of illness, rheumatoid factor is more likely to be negative with some individuals becoming seropositive over time. RF is a non-specific antibody and seen in about 10% of healthy people, in many other chronic infections like [[hepatitis C]], and chronic autoimmune diseases such as [[Sjögren's syndrome]] and [[systemic lupus erythematosus]]. Therefore, the test is not [[Specificity (tests)|specific]] for RA.<ref name="McGraw Hill"/>

Hence, new serological tests check for anti-citrullinated protein antibodies ACPAs. These tests are again positive in 61–75% of all RA cases, but with a specificity of around 95%.<ref>{{cite journal | vauthors = van Venrooij WJ, van Beers JJ, Pruijn GJ | s2cid = 11858403 | title = Anti-CCP antibodies: the past, the present and the future | journal = Nature Reviews. Rheumatology | volume = 7 | issue = 7 | pages = 391–398 | date = June 2011 | pmid = 21647203 | doi = 10.1038/nrrheum.2011.76 | hdl = 2066/91562 | hdl-access = free }}{{subscription required}}</ref> As with RF, ACPAs are many times present before symptoms have started.<ref name="McGraw Hill"/>

The by far most common clinical test for ACPAs is the anti-[[cyclic citrullinated peptide]] (anti CCP) ELISA. In 2008 a serological [[Point-of-care testing|point-of-care test]] for the early detection of RA combined the detection of RF and anti-MCV with a sensitivity of 72% and specificity of 99.7%.<ref>{{cite journal |vauthors=Renger F, Bang H, Fredenhagen G, et al |title=Anti-MCV Antibody Test for the Diagnosis of Rheumatoid Arthritis Using a POCT-Immunoassay |journal=American College of Rheumatology, 2008 Annual Scientific Meeting, Poster Presentation |url=http://acr.confex.com/acr/2008/webprogram/Paper2009.html |url-status=dead |archive-url=https://web.archive.org/web/20100527234743/http://acr.confex.com/acr/2008/webprogram/Paper2009.html |archive-date=2010-05-27 }}</ref>{{better source needed |date=July 2017}}<ref>{{cite journal | vauthors = Luime JJ, Colin EM, Hazes JM, Lubberts E | s2cid = 22283893 | title = Does anti-mutated citrullinated vimentin have additional value as a serological marker in the diagnostic and prognostic investigation of patients with rheumatoid arthritis? A systematic review | journal = Annals of the Rheumatic Diseases | volume = 69 | issue = 2 | pages = 337–344 | date = February 2010 | pmid = 19289382 | doi = 10.1136/ard.2008.103283 | url = http://ard.bmj.com/cgi/content/short/ard.2008.103283v1 }}{{subscription required}}</ref>

To improve the diagnostic capture rate in the early detection of patients with RA and to risk stratify these individuals, the rheumatology field continues to seek complementary markers to both RF and anti-CCP. 14-3-3η ([[YWHAH]]) is one such marker that complements RF and anti-CCP, along with other serological measures like [[C-reactive protein]]. In a systematic review, 14-3-3η has been described as a welcome addition to the rheumatology field. The authors indicate that the serum based 14-3-η marker is additive to the armamentarium of existing tools available to clinicians, and that there is adequate clinical evidence to support its clinical benefits.<ref>{{cite journal| vauthors = Abdelhafiz D, Kilborn S, Bukhari M | title = The role of 14-3-3 η as a biomarker in rheumatoid arthritis | journal = Rheumatology and Immunology Research. | date = June 2021 | volume = 2 | issue = 2 | pages = 87–90 | doi = 10.2478/rir-2021-0012 | pmid = 36465971 | pmc = 9524784 | s2cid = 238231522 }}</ref>

Other blood tests are usually done to differentiate from other causes of arthritis, like the [[erythrocyte sedimentation rate]] (ESR), C-reactive protein, [[full blood count]], [[kidney function]], [[liver enzyme]]s and other immunological tests (e.g., [[antinuclear antibody]]/ANA) are all performed at this stage. Elevated [[ferritin]] levels can reveal [[hemochromatosis]], a mimic of RA, or be a sign of [[Adult-onset Still's disease|Still's disease]], a seronegative, usually juvenile, variant of rheumatoid Arthritis.<ref>{{cite journal | vauthors = Barton JC, Barton JC | title = Autoimmune Conditions in 235 Hemochromatosis Probands with HFE C282Y Homozygosity and Their First-Degree Relatives | journal = Journal of Immunology Research | volume = 2015 | pages = 453046 | date = 2015 | pmid = 26504855 | pmc = 4609477 | doi = 10.1155/2015/453046 | doi-access = free }}</ref>

===Classification criteria===
In 2010, the ''2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria'' were introduced.<ref name=acr-eular>{{cite journal | vauthors = Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Ménard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G | s2cid = 1191830 | title = 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative | journal = Annals of the Rheumatic Diseases | volume = 69 | issue = 9 | pages = 1580–1588 | date = September 2010 | pmid = 20699241 | doi = 10.1136/ard.2010.138461 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/78045/1/27584_ftp.pdf | hdl = 2027.42/78045 | hdl-access = free }}</ref>

The new criteria are not diagnostic criteria, but are classification criteria to identify disease with a high likelihood of developing a chronic form.<ref name="McGraw Hill"/> However a score of 6 or greater unequivocally classifies a person with a diagnosis of rheumatoid arthritis.<ref>{{Cite journal |last1=Radu |first1=Andrei-Flavius |last2=Bungau |first2=Simona Gabriela |date=November 2021 |title=Management of Rheumatoid Arthritis: An Overview |journal=Cells |language=en |volume=10 |issue=11 |pages=2857 |doi=10.3390/cells10112857 |doi-access=free |pmid=34831081 |pmc=8616326 |issn=2073-4409}}</ref>

These new classification criteria overruled the "old" ACR criteria of 1987 and are adapted for early RA diagnosis. The "new" classification criteria, jointly published by the [[American College of Rheumatology]] (ACR) and the [[European League Against Rheumatism]] (EULAR) establish a point value between 0 and 10. Four areas are covered in the diagnosis:<ref name=acr-eular/>
* joint involvement, designating the [[metacarpophalangeal joint]]s, [[proximal interphalangeal joint]]s, the [[interphalangeal articulations of hand|interphalangeal joint]] of the thumb, second through fifth [[metatarsophalangeal joint]] and [[wrist]] as ''small joints'', and [[shoulder]]s, [[elbow]]s, [[hip joint]]s, [[knee]]s, and [[ankle]]s as ''large joints'':
** Involvement of 1 large joint gives 0 points
** Involvement of 2–10 large joints gives 1 point
** Involvement of 1–3 small joints (with or without involvement of large joints) gives 2 points
** Involvement of 4–10 small joints (with or without involvement of large joints) gives 3 points
** Involvement of more than 10 joints (with involvement of at least 1 small joint) gives 5 points
* serological parameters – including the [[rheumatoid factor]] as well as [[anti-citrullinated protein antibody|ACPA]] – "ACPA" stands for "anti-citrullinated protein antibody":
** Negative RF ''and'' negative ACPA gives 0 points
** Low-positive RF ''or'' low-positive ACPA gives 2 points
** High-positive RF ''or'' high-positive ACPA gives 3 points
* acute phase reactants: 1 point for elevated erythrocyte sedimentation rate, [[Erythrocyte sedimentation rate|ESR]], or elevated [[C-reactive protein|CRP]] value (c-reactive protein)
* duration of [[arthritis]]: 1 point for symptoms lasting six weeks or longer

The new criteria accommodate to the growing understanding of RA and the improvements in diagnosing RA and disease treatment. In the "new" criteria, serology and [[autoimmune disease|autoimmune diagnostics]] carries major weight, as ACPA detection is appropriate to diagnose the disease in an early state, before joints destructions occur. Destruction of the joints viewed in radiological images was a significant point of the ACR criteria from 1987.<ref>{{cite journal | vauthors = Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS | title = The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis | journal = Arthritis and Rheumatism | volume = 31 | issue = 3 | pages = 315–34 | date = March 1988 | pmid = 3358796 | doi = 10.1002/art.1780310302 | doi-access = free }}</ref> This criterion no longer is regarded to be relevant, as this is just the type of damage that treatment is meant to avoid.

===Differential diagnoses===
{{Synovial fluid analysis}}
Several other medical conditions can resemble RA, and need to be distinguished from it at the time of diagnosis:<ref name=Merckmanual>{{cite book | editor=Berkow R | title=The Merck Manual | edition=16th | publisher=Merck Publishing Group | year=1992 | pages=1307–1308 | isbn=978-0-911910-16-2 | url=https://archive.org/details/merckmanualofdia16berk }}{{subscription required}}</ref>
* Crystal induced arthritis ([[gout]], and [[pseudogout]]) – usually involves particular joints (knee, MTP1, heels) and can be distinguished with an aspiration of joint fluid if in doubt. Redness, asymmetric distribution of affected joints, pain occurs at night and the starting pain is less than an hour with gout.
* [[Osteoarthritis]] – distinguished with [[X-ray]]s of the affected joints and blood tests, older age, starting pain less than an hour, asymmetric distribution of affected joints and pain worsens when using joint for longer periods.
* [[Systemic lupus erythematosus]] (SLE) – distinguished by specific clinical symptoms and blood tests (antibodies against double-stranded DNA)
* One of the several types of [[psoriatic arthritis]] resembles RA – nail changes and skin symptoms distinguish between them
* [[Lyme disease]] causes erosive arthritis and may closely resemble RA – it may be distinguished by blood test in endemic areas
* [[Reactive arthritis]] – asymmetrically involves heel, [[sacroiliac]] joints and large joints of the leg. It is usually associated with [[urethritis]], [[conjunctivitis]], [[iritis]], painless buccal ulcers, and [[keratoderma blennorrhagica]].
* [[Axial spondyloarthritis]] (including [[ankylosing spondylitis]]) – this involves the spine, although an RA-like symmetrical small-joint polyarthritis may occur in the context of this condition.
* [[Hepatitis C]] – RA-like symmetrical small-joint polyarthritis may occur in the context of this condition. Hepatitis C may also induce rheumatoid factor auto-antibodies.

Rarer causes which usually behave differently but may cause joint pains:<ref name=Merckmanual/>
* [[Sarcoidosis]], [[amyloidosis]], and [[Whipple's disease]] can also resemble RA.
* [[Hemochromatosis]] may cause hand joint arthritis.
* Acute rheumatic fever can be differentiated by a migratory pattern of joint involvement and evidence of antecedent [[streptococcal]] infection.
* Bacterial arthritis (such as by ''[[Streptococcus]]'') is usually asymmetric, while RA usually involves both sides of the body symmetrically.
* [[Gonococcal]] arthritis (a bacterial arthritis) is also initially migratory and can involve [[tendon]]s around the wrists and ankles.

Sometimes arthritis is in an undifferentiated stage (i.e. none of the above criteria is positive), even if synovitis is witnessed and assessed with ultrasound imaging.

=== Difficult-to-treat ===
Rheumatoid arthritis (D2T RA) is a specific classification RA by the European League against Rheumatism ([[EULAR]]).<ref>{{cite journal | vauthors = Roodenrijs NM, Welsing PM, van der Goes MC, Jacobs JW, van der Heijde D, van Laar JM, Nagy G | title = Response to: 'Correspondence on EULAR definition of difficult-to-treat rheumatoid arthritis' by Novella-Navarro et al. | journal = Annals of the Rheumatic Diseases | pages = annrheumdis–2020–219535 | date = December 2020 | volume = 82 | issue = 3 | pmid = 33277239 | doi = 10.1136/annrheumdis-2020-219535 | s2cid = 227275679 | hdl = 1887/3594609 | hdl-access = free }}</ref>

Signs of illness:

# Persistence of signs and symptoms
# [[Drug resistance]]
# Does not respond on two or more biological treatments
# Does not respond on anti-rheumatic drugs with different mechanism of action

Factors contributing to difficult-to-treat disease:

# Genetic risk factors
# Environmental factors (diet, smoking, physical activity)
# Overweight and obese

===Genetic factors===

Genetic factors such as HLA-DR1B1,<ref>{{cite journal | vauthors = Raychaudhuri S | title = Recent advances in the genetics of rheumatoid arthritis | journal = Current Opinion in Rheumatology | volume = 22 | issue = 2 | pages = 109–118 | date = March 2010 | pmid = 20075733 | pmc = 3121048 | doi = 10.1097/bor.0b013e328336474d }}</ref> [[TRAF1]], PSORS1C1 and [[microRNA]] 146a<ref>{{cite journal | vauthors = Conigliaro P, Triggianese P, De Martino E, Fonti GL, Chimenti MS, Sunzini F, Viola A, Canofari C, Perricone R | title = Challenges in the treatment of Rheumatoid Arthritis | journal = Autoimmunity Reviews | volume = 18 | issue = 7 | pages = 706–713 | date = July 2019 | pmid = 31059844 | doi = 10.1016/j.autrev.2019.05.007 | hdl-access = free | s2cid = 146811143 | hdl = 2108/225718 }}</ref> are associated with difficult to treat rheumatoid arthritis, other gene polymorphisms seem to be correlated with response to biologic modifying anti-rheumatic drugs (bDMARDs). Next one is FOXO3A gene region been reported as associated with worst disorder. The minor allele at FOXO3A summon a differential response of monocytes in RA patients. FOXO3A can provide an increase of pro-inflammatory cytokines, including TNFα. Possible gene polymorphism: STAT4, PTPN2, PSORS1C1 and TRAF3IP2 genes had been correlated with response to TNF inhibitors.<ref>{{cite journal |last1=Conigliaro |first1=Paola |last2=Ciccacci |first2=Cinzia |last3=Politi |first3=Cristina |last4=Triggianese |first4=Paola |last5=Rufini |first5=Sara |last6=Kroegler |first6=Barbara |last7=Perricone |first7=Carlo |last8=Latini |first8=Andrea |last9=Novelli |first9=Giuseppe |last10=Borgiani |first10=Paola |last11=Perricone |first11=Roberto |date=2017-01-20 |editor-last=Ahuja |editor-first=Sunil K |title=Polymorphisms in STAT4, PTPN2, PSORS1C1 and TRAF3IP2 Genes Are Associated with the Response to TNF Inhibitors in Patients with Rheumatoid Arthritis |journal=PLOS ONE |language=en |volume=12 |issue=1 |pages=e0169956 |doi=10.1371/journal.pone.0169956 |issn=1932-6203 |pmc=5249113 |pmid=28107378 |bibcode=2017PLoSO..1269956C |doi-access=free }}</ref>

===HLA-DR1 and HLA-DRB1 gene===

The ''HLA''-''DRB1'' gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex is the human version of the major histocompatibility complex (MHC). Currently, have been identified at least 2479 different versions of the ''HLA''-''DRB1'' gene.<ref>{{cite journal | vauthors = Klimenta B, Nefic H, Prodanovic N, Jadric R, Hukic F | title = Association of biomarkers of inflammation and HLA-DRB1 gene locus with risk of developing rheumatoid arthritis in females | journal = Rheumatology International | volume = 39 | issue = 12 | pages = 2147–2157 | date = December 2019 | pmid = 31451934 | doi = 10.1007/s00296-019-04429-y | s2cid = 201644677 }}</ref> The presence of HLA-DRB1 alleles seems to predict radiographic damage, which may be partially mediated by ACPA development, and also elevated sera inflammatory levels and high swollen joint count. HLA-DR1 is encoded by the most risk allele [[HLA-DRB1]] which share a conserved 5-aminoacid sequence that is correlated with the development of anti-citrullinated protein antibodies.<ref>{{cite journal | vauthors = Gregersen PK, Silver J, Winchester RJ | title = The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis | journal = Arthritis and Rheumatism | volume = 30 | issue = 11 | pages = 1205–1213 | date = November 1987 | pmid = 2446635 | doi = 10.1002/art.1780301102 | doi-access = free }}</ref> HLA-DRB1 gene have more strong correlation with disease development. Susceptibility to and outcome for rheumatoid arthritis (RA) may associate with particular HLA-DR alleles, but these alleles vary among ethnic groups and geographic areas.<ref>{{cite journal | vauthors = Kapitány A, Zilahi E, Szántó S, Szücs G, Szabó Z, Végvári A, Rass P, Sipka S, Szegedi G, Szekanecz Z | title = Association of rheumatoid arthritis with HLA-DR1 and HLA-DR4 in Hungary | journal = Annals of the New York Academy of Sciences | volume = 1051 | issue = 1 | pages = 263–270 | date = June 2005 | pmid = 16126967 | doi = 10.1196/annals.1361.067 | s2cid = 6515443 | bibcode = 2005NYASA1051..263K }}</ref>

===MicroRNAs===

MicroRNAs are a factor in the development of that type of disease. MicroRNAs usually operate as a negative regulator of the expression of target proteins and their increased concentration after biologic treatment (bDMARDs) or after anti-rheumatic drugs. Level of miRNA before and after anti-TNFa/DMRADs combination therapy are potential novel biomarkers for predicting and monitoring outcome. For instance, some of them were found significantly upregulated by anti-TNFa/DMRADs combination therapy. For example, miRNA-16-5p, miRNA-23-3p, miRNA125b-5p, miRNA-126-3p, miRNA-146a-5p, miRNA-223-3p. Curious fact is that only responder patients showed an increase in those miRNAs after therapy, and paralleled the reduction of TNFα, interleukin (IL)-6, IL-17, rheumatoid factor (RF), and C-reactive protein (CRP).<ref>{{cite journal | vauthors = Castro-Villegas C, Pérez-Sánchez C, Escudero A, Filipescu I, Verdu M, Ruiz-Limón P, Aguirre MA, Jiménez-Gomez Y, Font P, Rodriguez-Ariza A, Peinado JR, Collantes-Estévez E, González-Conejero R, Martinez C, Barbarroja N, López-Pedrera C | title = Circulating miRNAs as potential biomarkers of therapy effectiveness in rheumatoid arthritis patients treated with anti-TNFα | journal = Arthritis Research & Therapy | volume = 17 | issue = 1 | pages = 49 | date = March 2015 | pmid = 25860297 | pmc = 4377058 | doi = 10.1186/s13075-015-0555-z | doi-access = free }}</ref>

===Monitoring progression===

Many tools can be used to monitor remission in rheumatoid arthritis.
* DAS28: ''Disease Activity Score of 28 joints'' ({{visible anchor|DAS28}}) is widely used as an indicator of RA disease activity and response to treatment. Joints included are ([[bilateral symmetry|bilaterally]]): [[proximal interphalangeal joint]]s (10 joints), [[metacarpophalangeal joint]]s (10), [[wrist]]s (2), [[elbow]]s (2), [[shoulder]]s (2) and [[knee]]s (2). When looking at these joints, both the number of joints with tenderness upon touching (TEN28) and swelling (SW28) are counted. The [[erythrocyte sedimentation rate]] (ESR) is measured and the affected person makes a subjective assessment (SA) of disease activity during the preceding 7 days on a scale between 0 and 100, where 0 is "no activity" and 100 is "highest activity possible". With these parameters, DAS28 is calculated as:<ref name=Prevoo1995/>
<math>DAS28=0.56 \times \sqrt{TEN28} + 0.28 \times \sqrt{SW28} + 0.70 \times \ln(ESR) + 0.014 \times SA</math>

From this, the disease activity of the affected person can be classified as follows:<ref name=Prevoo1995>{{cite journal | vauthors = Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL | title = Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis | journal = Arthritis and Rheumatism | volume = 38 | issue = 1 | pages = 44–48 | date = January 1995 | pmid = 7818570 | doi = 10.1002/art.1780380107 | url = http://www.pharmacoeconomics.ru/jour/article/view/135 | hdl = 2066/20651 | s2cid = 11192145 | hdl-access = free }}{{subscription required}}</ref>
{|class="wikitable"
|-
!colspan=2 rowspan=2| Current <br>DAS28 !!colspan=3| DAS28 decrease from initial value
|-
| [[more than|>]] 1.2 || > 0.6 but [[less than or equal to|≤]] 1.2 || ≤ 0.6
|-
| [[less than or equal to|≤]] 3.2 || Inactive || Good improvement || Moderate improvement || No improvement
|-
| [[more than|>]] 3.2 but ≤ 5.1 || Moderate || Moderate improvement || Moderate improvement || No improvement
|-
| > 5.1 || Very active || Moderate improvement || No improvement || No improvement
|}

It is not always a reliable indicator of treatment effect.<ref>Kelly, Janis (22 February 2005) [http://www.medscape.com/viewarticle/538134 DAS28 not always a reliable indicator of treatment effect in RA] {{webarchive|url=https://web.archive.org/web/20110225054141/http://www.medscape.com/viewarticle/538134 |date=2011-02-25 }}, Medscape Medical News.</ref> One major limitation is that low-grade synovitis may be missed.<ref>{{cite journal | vauthors= Uribe L, Cerón C, Amariles P, Llano JF, Restrepo M, Montoya N, González LA, Díaz OJ, Saldarriaga MA, Gómez-Puerta JA |date=July–September 2016 |title=Correlación entre la actividad clínica por DAS-28 y ecografía en pacientes con artritis reumatoide |trans-title=Correlation between clinical activity measured by DAS-28 and ultrasound in patients with rheumatoid arthritis |journal=Revista Colombiana de Reumatología |volume=23 |issue=3 |pages=159–169 |language=es |doi=10.1016/j.rcreu.2016.05.002 }}</ref>
* Other: Other tools to monitor remission in rheumatoid arthritis are: ACR-EULAR Provisional Definition of Remission of Rheumatoid arthritis, Simplified Disease Activity Index and Clinical Disease Activity Index.<ref>{{cite journal | vauthors = Yazici Y, Simsek I | title = Tools for monitoring remission in rheumatoid arthritis: any will do, let's just pick one and start measuring | journal = Arthritis Research & Therapy | volume = 15 | issue = 1 | pages = 104 | date = January 2013 | pmid = 23374997 | pmc = 3672754 | doi = 10.1186/ar4139 | doi-access = free }}{{subscription required}}</ref> Some scores do not require input from a healthcare professional and allow self-monitoring by the person, like HAQ-DI.<ref>{{cite journal | vauthors = Bruce B, Fries JF | title = The Stanford Health Assessment Questionnaire: dimensions and practical applications | journal = Health and Quality of Life Outcomes | volume = 1 | pages = 20 | date = June 2003 | pmid = 12831398 | pmc = 165587 | doi = 10.1186/1477-7525-1-20 | doi-access = free }}{{subscription required}}</ref>{{page needed|date=July 2017}}