Skip to main content

Main menu

  • Home
  • Content
    • First Release
    • Current
    • Archives
    • Collections
    • Audiovisual Rheum
    • COVID-19 and Rheumatology
  • Resources
    • Guide for Authors
    • Submit Manuscript
    • Payment
    • Reviewers
    • Advertisers
    • Classified Ads
    • Reprints and Translations
    • Permissions
    • Meetings
    • FAQ
    • Policies
  • Subscribers
    • Subscription Information
    • Purchase Subscription
    • Your Account
    • Terms and Conditions
  • About Us
    • About Us
    • Editorial Board
    • Letter from the Editor
    • Duncan A. Gordon Award
    • Privacy/GDPR Policy
    • Accessibility
  • Contact Us
  • JRheum Supplements
  • Services

User menu

  • My Cart
  • Log In

Search

  • Advanced search
The Journal of Rheumatology
  • JRheum Supplements
  • Services
  • My Cart
  • Log In
The Journal of Rheumatology

Advanced Search

  • Home
  • Content
    • First Release
    • Current
    • Archives
    • Collections
    • Audiovisual Rheum
    • COVID-19 and Rheumatology
  • Resources
    • Guide for Authors
    • Submit Manuscript
    • Payment
    • Reviewers
    • Advertisers
    • Classified Ads
    • Reprints and Translations
    • Permissions
    • Meetings
    • FAQ
    • Policies
  • Subscribers
    • Subscription Information
    • Purchase Subscription
    • Your Account
    • Terms and Conditions
  • About Us
    • About Us
    • Editorial Board
    • Letter from the Editor
    • Duncan A. Gordon Award
    • Privacy/GDPR Policy
    • Accessibility
  • Contact Us
  • Follow jrheum on Twitter
  • Visit jrheum on Facebook
  • Follow jrheum on LinkedIn
  • Follow jrheum on YouTube
  • Follow jrheum on Instagram
  • Follow jrheum on RSS
Research ArticleRheumatoid Arthritis

Cervical Spine Involvement among Patients with Rheumatoid Arthritis Treated Actively with Treat-to-target Strategy: 10-year Results of the NEO-RACo Study

Tia Sandström, Vappu Rantalaiho, Timo Yli-Kerttula, Hannu Kautiainen, Timo Malmi, Anna Karjalainen, Tea Uusitalo, Heikki Julkunen, Oili Kaipiainen-Seppänen, Leena Paimela, Kari Puolakka, Toini Uutela, Timo Möttönen, Pekka Hannonen, Marjatta Leirisalo-Repo, Leena Laasonen, Markku Kauppi and for the NEO-RACo Study Group
The Journal of Rheumatology August 2020, 47 (8) 1160-1164; DOI: https://doi.org/10.3899/jrheum.190139
Tia Sandström
From the Department of Rheumatology, and the Helsinki Medical Imaging Center, Helsinki University Hospital and University of Helsinki, Helsinki; Centre for Rheumatic Diseases, Tampere University Hospital; Faculty of Medicine and Health Technology, Tampere University, Tampere; Department of Rheumatology, Satakunta Central Hospital, Rauma; Primary Health Care Unit, Kuopio University Hospital, Kuopio; Folkhälsan Research Center, Helsinki; Department of Medicine, Seinäjoki Central Hospital, Seinäjoki; Department of Rheumatology, Oulu University Hospital and University of Oulu, Oulu; Department of Medicine, Hämeenlinna Central Hospital, Hämeenlinna; Department of Medicine, Kuopio University Hospital, Kuopio, Finland; Orton Orthopaedic Hospital, Helsinki; South Karelia Central Hospital, Lappeenranta; Department of Medicine, Lapland Central Hospital, Rovaniemi; School of Medicine, University of Turku, Turku; Department of Rheumatology, Central Hospital of Central Finland, Jyväskylä; Department of Rheumatology, Päijät-Häme Central Hospital, Lahti, Finland.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tia Sandström
  • For correspondence: tia.sandstrom@hus.fi
Vappu Rantalaiho
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Vappu Rantalaiho
Timo Yli-Kerttula
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Timo Yli-Kerttula
Hannu Kautiainen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Timo Malmi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna Karjalainen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Anna Karjalainen
Tea Uusitalo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tea Uusitalo
Heikki Julkunen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Heikki Julkunen
Oili Kaipiainen-Seppänen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Oili Kaipiainen-Seppänen
Leena Paimela
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kari Puolakka
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Toini Uutela
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Timo Möttönen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Timo Möttönen
Pekka Hannonen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marjatta Leirisalo-Repo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Marjatta Leirisalo-Repo
Leena Laasonen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Markku Kauppi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Markku Kauppi
  • Article
  • Figures & Data
  • Info & Metrics
  • References
  • PDF
  • eLetters
PreviousNext
Loading

Abstract

Objective. To evaluate the development of radiological changes of the cervical spine in patients with rheumatoid arthritis (RA) in the NEO-RACo trial treated with an intensive, remission-targeted combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and additional infliximab (IFX) or placebo (PLA) for the first 6 months.

Methods. Ninety-nine patients with early, DMARD-naive RA were treated with a triple combination of csDMARD and prednisolone, and randomized to double-blindly receive either IFX (FIN-RACo+IFX) or PLA (FIN-RACo+PLA) infusions during the first 6 months. After 2 years the treatment strategies became unrestricted, but the treatment goal was strict NEO-RACo remission. At the 10-year visit, radiographs of the cervical spine were taken of 85 patients (38 in the FIN-RACo+IFX group and 47 in the FIN-RACo+PLA group). The study was registered at ClinicalTrials.gov (NCT 00908089).

Results. There were 4/85 patients (4.7%) with cervical spine involvement (CSI) by 10 years. Atlantoaxial subluxation was found in 2/85 patients (2.4%), both in the FIN-RACo+IFX group, and none in the FIN-RACo+PLA group. Atlantoaxial impaction was found in 1/85 patients (1.2%) in the FIN-RACo+IFX group. Subaxial subluxation was found in 1/85 patients (1.2%).

Conclusion. Early and intensive remission-targeted treatment has reduced the incidence of CSI and our results show that intensive treatment also prevents its development in the long run.

Key Indexing Terms:
  • RHEUMATOID ARTHRITIS
  • CERVICAL SPINE
  • TREATMENT
  • ATLANTOAXIAL SUBLUXATION
  • DISEASE-MODIFYING ANTIRHEUMATIC DRUG

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that primarily affects the peripheral small joints. The cervical spine is also commonly affected1. Clinically the most important changes in the cervical spine are anterior atlantoaxial subluxation (aAAS), atlantoaxial impaction (AAI), and subaxial subluxation (SAS)1,2,3. Cervical vertebrae 1 and 2 (C1 and C2) or the atlas and axis articulation is one of the prime targets for rheumatoid pannus formation. This leads to bone destruction and laxity in the ligamentous complex leading to AAS1,4,5. The subluxation can be anterior, posterior, lateral, and rotatory, of which anterior subluxation is the most common1. AAI results from cartilage and bone erosions of the occiput (C0)–C1 and C1–2 joints, leading to superior migration of the dens of axis1,3,5. SAS results from destruction of the facet joints, interspinous ligaments, and intervertebral discs causing subluxation at 1 or multiple levels1,4,5. Cervical spine involvement (CSI) can, if left untreated, lead to severe and potentially life-threatening complications6,7. The natural course of cervical spine lesions shows a progressive pattern, and a combination with AAS and AAI or SAS is common in patients with RA1,8,9. Development of CSI has been associated with inflammatory activity and severity of RA3,7,9,10,11,12,13,14. If CSI is suspected, cervical spine radiographs taken during flexion is the method of choice for examination, because both radiographs taken in a neutral position15 and functional magnetic resonance imaging taken in a supine position16 fail to recognize all aAAS findings.

CSI is typically a late manifestation of RA, occurring in patients with longstanding erosive disease5, but there have also been studies showing that CSI begins early in the course of RA9,17. The prevalence of CSI in RA patients with longterm followup range widely from 16% to 88% depending on the studied population, disease characteristics, disease management, and followup time1,2,3,4,5,9,10,11,12,17. The prevalence has been shown to increase over time in ineffectively treated patients. Early and effective treatment with conventional synthetic (cs) or biologic (b) disease-modifying antirheumatic drugs (DMARD) reduces the prevalence of CSI1,2,3,10,12. However, csDMARD and bDMARD may be unable to prevent the progression of preexisting CSI4,7.

In the NEO-RACo trial, all patients with early RA were treated initially by a combination of csDMARD, methotrexate (MTX), sulfasalazine (SSZ), hydroxychloroquine (HCQ), and low-dose prednisolone (PSL) for 2 years, and in addition double-blindly randomized to receive either infliximab (IFX) or placebo (PLA) infusions for the first 6 months. Thereafter the treatment strategy with DMARD and glucocorticoids (GC) became unrestricted, aiming at all times at remission. This treatment strategy resulted in excellent clinical and radiographic (hands and feet) outcomes at 2, 5, and even at 10 years18,19,20. At 10 years the proportion of patients in strict NEO-RACo remission were 46% in the FIN-RACo+IFX group and 38% in the FIN-RACo+PLA group. In the 28-joint count Disease Activity Score (DAS28) remission the proportions were 82% and 72%, respectively. The mean total Sharp/van der Heijde score (SvdH) in the FIN-RACo+IFX group was 9.8 and in the FIN-RACo+PLA group, 7.320.

To our knowledge, there are no treat-to-target trials with longterm followup assessing the development of CSI in early RA. In our study we evaluated the development of radiological changes of the cervical spine in patients with early RA participating in the NEO-RACo trial.

MATERIALS AND METHODS

Study design and patients

In this investigator-initiated, multicenter study, 99 patients were recruited between March 2003 to April 2005. These patients were DMARD- and GC-naive with early, active RA [patients who fulfilled the American College of Rheumatology 1987 classification criteria for RA21, had symptoms for ≤ 12 months, had ≥ 6 swollen (66 joint count) and ≥ 6 tender (68 joint count) joints] and at least 1 of the following: early morning stiffness duration ≥ 45 min, erythrocyte sedimentation rate (ESR) ≥ 30 mm/h, or C-reactive protein ≥ 20 mg/l. They were treated with an intensified FIN-RACo regimen (MTX up to 25 mg/week, SSZ up to 2 g/day, HCQ 35 mg/kg/week, and PSL 7.5 mg/day) for 2 years and in addition double-blindly randomized to receive either IFX or PLA infusions at weeks 4, 6, 10, 18, and 26. An active use of intraarticular GC injections to all inflamed joints was part of the protocol. If the patient was in strict NEO-RACo remission at the 2-year visit, PSL was gradually tapered, followed by a slow decrease in the doses and number of DMARD. The therapies could be modified according to the judgment of the treating rheumatologist, using all available csDMARD, bDMARD and GC, aiming at all times, during the 10-year followup, at strict NEO-RACo remission. The patient was considered in strict NEO-RACo remission if 5 out of the following 6 criteria were present: morning stiffness < 15 min, no fatigue, no joint pain, no tender joints, no swollen joints, and ESR < 30 mm/h in women and < 20 mm/h in men. Patient selection and criteria as well as the treatment protocol were described in more detail earlier18. The study protocol was approved by the national health authorities and by the ethics committee of the Hospital District of Helsinki and Uusimaa (approval number 676/E5/02). The study was conducted according to the Declaration of Helsinki. All patients gave informed written consent. The study was registered at ClinicalTrials.gov (NCT 00908089).

Radiological examination

Radiographs of the hands and feet were taken at baseline and at 2, 5, 7, and 10 years, and scored according to the modified SvdH. Lateral-view cervical spine radiographs during flexion and extension were taken at baseline and at 10 years. Of the 99 patients, 86 remained in the study at 10 years and radiographs of the cervical spine were taken of 85 patients (38 in the FIN-RACo+IFX group and 47 in the FIN-RACo+PLA group). The baseline data of the dropouts did not differ from the baseline data of those who continued in the trial (data not shown). The radiographs were read by an experienced radiologist (LL), aware of the chronology of the radiographs but blinded for the treatment arm and clinical data. AAS was diagnosed if the distance between the anterior aspect of the dens of the axis and the posterior aspect of the anterior arch of the atlas was > 3 mm during flexion. The evaluation of AAI was made from lateral-view radiographs taken during flexion. AAI was diagnosed using the Sakaguchi-Kauppi (SK) method, developed especially for screening purposes, which evaluates the position of the atlas in relation to the axis22. The SK method divides AAI into 4 grades; grade I represents normal and grades II–IV abnormal. A diagnosis of SAS was made if a vertebra had moved > 3 mm relative to the next vertebra as measured from the posterior line of the vertebral bodies.

Statistical analysis

Data are presented as means with SD or as counts with percentages. Statistical comparisons between the groups were made using the t test, chi-square test, or Fisher’s exact test. A bootstrap method was used when the theoretical distribution of the test statistics was unknown or in the case of a violation of the assumptions (e.g., non-normality). The Stata 14.1 (StataCorp LP) statistical package was used for the analysis.

RESULTS

Table 1 shows the demographic data, clinical characteristics, and radiographic (feet and hands) findings at baseline of the 2 patient groups. At baseline, radiographs of the cervical spine were also taken with normal findings in all the patients.

View this table:
  • View inline
  • View popup
Table 1.

Demographic data, clinical characteristics, and radiographic findings at baseline in patients randomized to receive initial infliximab (FIN-RACo+IFX) or initial placebo infusions (FIN-RACo+PLA) for 6 months in addition to a combination of 3 DMARD and low-dose prednisolone.

At 10 years, 4 (4.7%) of the 85 patients with cervical spine radiographs (38 in the FIN-RACo+IFX group and 47 in the FIN-RACo+PLA group) had slight CSI. AAS was found in 2/85 patients (2.4%), both in the FIN-RACo+IFX group. Both AAS cases were slight (3.1 mm and 3.9 mm). One (1.2%) in the FIN-RACo+IFX group had a slight (SK grade II) AAI, and 1 case with slight SAS (1.2%; 3.5 mm) was found in the FIN-RACo+PLA group. Table 2 shows the characteristics of the 4 patients with CSI at baseline, and at 10 years. All 4 patients with CSI were seropositive and entered rapidly into sustained remission during the whole followup time. No difference was found in the annual cumulative area under the curve of DAS28 from baseline to 10 years between the patients with CSI (2.03, SD 0.59) and those without (2.00, SD 0.71; p = 0.59). Neither was there any difference in the baseline ages of the patients: 47 ± 10 years versus 45 ± 8 years, respectively (p = 0.67).

View this table:
  • View inline
  • View popup
Table 2.

Main characteristics of the 4 patients who developed cervical spine involvement at the 10-year followup.

DISCUSSION

To our knowledge, there are no present-day treat-to-target trials with longterm followup on CSI in early RA. We show here that CSI is very rare in actively treated patients with RA even in longterm followup. This suggests that modern effective treatment does prevent the development of clinically significant CSI.

CSI in longterm followup has been rather common in historical RA cohorts. In old studies, the prevalence of AAS has been 10% already after 2 years of RA23. Paimela, et al9 reported 30% of patients with RA having developed CSI in 6.5 years despite active treatment with csDMARD from the diagnosis, and Neva, et al24 found a percentage of 42 after 20 years in patients treated with csDMARD. Since then, the prevalence has been declining concurrent with earlier and more intensive use of DMARD. In the FIN-RACo study, only 10% of the patients treated initially with a combination of 3 DMARD developed CSI after 5 years versus 26% of the patients treated initially with a single DMARD, even though treatment strategies were unrestricted after 2 years3. In this NEO-RACo study, the result was even better than in the FIN-RACo study. Compared with the FIN-RACo study, the patients in the NEO-RACo trial started treatment earlier, the remission target was stricter and thus treatment was more intensive including also the availability of bDMARD.

Development of CSI has been associated with positive rheumatoid factor, peripheral joint erosions, previous joint surgery, markers of high disease activity, poor functional capacity by the Health Assessment Questionnaire, long duration of RA, low body mass index, DMARD failure, and longterm GC treatment3,4,7,9,10,11,12,13,14. In the NEO-RACo trial, all patients were treated actively to target throughout the 10-year followup. Most patients, regardless of treatment group, achieved very low disease activity and preserved their functional ability at 2, 5, and even at 10 years, and had minimal to no radiographic joint damage progression. Thus in the present study, only 4.7% of the patients with incident, very active RA had slight CSI after 10 years, and the findings have presumably no clinical significance. All 4 patients with CSI were in remission during the followup; only one of the patients had significant progression of the SvdH in radiographs of the hands and feet. Owing to a low number of CSI findings, no associations or predictive factors for CSI could be calculated.

The limitation of our study is the small study population size and the lack of a control group who were treated less actively during followup. It is also a limitation that spinal radiographs have been read with a known time order and by only 1 reader. The random reading and the use of 2 readers might have increased the accuracy of the results. The strengths of our study are that the patients were treated actively from the diagnosis and the majority was followed up prospectively up to 10 years.

CSI is very rare in patients with early RA treated with intensive treat-to-target strategy and active modification of treatment during followup. Based on this, routine radiological screening is not needed even after 10 years of disease duration in analogous patient cohorts. However, in real life there are many patients whom rheumatologists are not personally following up from initial diagnosis to 10 years. Understanding what the disease activity burden over time in such patients has been may be challenging. CSI should still be kept in mind in patients with persistently high disease activity or in disabled patients, those with deformities, or those with a long history of active RA.

Acknowledgment

The authors thank all participating patients, other members of the NEO-RACo Study Group [Eeva Alasaarela, Harri Blåfield, Kari K. Eklund, Mikko Hakola, Kirsti Ilva, Markku Korpela, Maija-Liisa Krogerus, Kari Laiho, Riitta Luosujärvi, Reijo Luukkainen, Helena Niinisalo, Ritva Peltomaa, Heikki Valleala, Kaisa Vuori (rheumatologists) and Eeva Moilanen, Riina Nieminen, Katariina Vuolteenaho (pharmacologists)], and study nurses for their contribution.

Footnotes

  • This study was financially supported by the Competitive Research Funding of Tampere University Hospital, the Helsinki University Central Hospital Research Funds, Finska Läkaresällskapet, Liv och Hälsa, and the Finnish Society for Rheumatology. At baseline, an unrestricted grant was provided by Schering-Plough Finland, which was used for the purchase of infliximab. Schering-Plough Finland also provided support for investigator meetings. The funders did not have any role in the study design, data collection and analysis, preparation of the manuscript, or decision to publish.

  • Accepted for publication November 5, 2019.

REFERENCES

  1. 1.↵
    1. Zhang T,
    2. Pope J
    . Cervical spine involvement in rheumatoid arthritis over time: results from a meta-analysis. Arthritis Res Ther 2015;17:148.
    OpenUrl
  2. 2.↵
    1. Neva MH,
    2. Kauppi MJ,
    3. Kautiainen H,
    4. Luukkainen R,
    5. Hannonen P,
    6. Leirisalo-Repo M,
    7. et al;
    8. FIN-RACo Trial Group
    . Combination drug therapy retards the development of rheumatoid atlantoaxial subluxations. Arthritis Rheum 2000;43:2397–401.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Kauppi MJ,
    2. Neva MH,
    3. Laiho K,
    4. Kautiainen H,
    5. Luukkainen R,
    6. Karjalainen A,
    7. et al;
    8. FIN-RACo Trial Group
    . Rheumatoid atlantoaxial subluxation can be prevented by intensive use of traditional disease modifying antirheumatic drugs. J Rheumatol 2009;36:273–8.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Joaquim AF,
    2. Appenzeller S
    . Cervical spine involvement in rheumatoid arthritis--a systematic review. Autoimmun Rev 2014;13:1195–202.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Kim HJ,
    2. Nemani VM,
    3. Riew KD,
    4. Brasington R
    . Cervical spine disease in rheumatoid arthritis: incidence, manifestations, and therapy. Curr Rheumatol Rep 2015;17:9.
    OpenUrl
  6. 6.↵
    1. Neva MH,
    2. Hakkinen A,
    3. Makinen H,
    4. Hannonen P,
    5. Kauppi M,
    6. Sokka T
    . High prevalence of asymptomatic cervical spine subluxation in patients with rheumatoid arthritis waiting for orthopaedic surgery. Ann Rheum Dis 2006;65:884–8.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. Gillick JL,
    2. Wainwright J,
    3. Das K
    . Rheumatoid arthritis and the cervical spine: a review on the role of surgery. Int J Rheumatol 2015;2015:252456.
    OpenUrl
  8. 8.↵
    1. Oda T,
    2. Fujiwara K,
    3. Yonenobu K,
    4. Azuma B,
    5. Ochi T
    . Natural course of cervical spine lesions in rheumatoid arthritis. Spine 1995;20:1128–35.
    OpenUrlPubMed
  9. 9.↵
    1. Paimela L,
    2. Laasonen L,
    3. Kankaanpaa E,
    4. Leirisalo-Repo M
    . Progression of cervical spine changes in patients with early rheumatoid arthritis. J Rheumatol 1997;24:1280–4.
    OpenUrlPubMed
  10. 10.↵
    1. Neva MH,
    2. Isomaki P,
    3. Hannonen P,
    4. Kauppi M,
    5. Krishnan E,
    6. Sokka T
    . Early and extensive erosiveness in peripheral joints predicts atlantoaxial subluxations in patients with rheumatoid arthritis. Arthritis Rheum 2003;48:1808–13.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Terashima Y,
    2. Yurube T,
    3. Hirata H,
    4. Sugiyama D,
    5. Sumi M;
    6. Hyogo Organization of Spinal Disorders
    . Predictive risk factors of cervical spine instabilities in rheumatoid arthritis: a prospective multicenter over 10-year cohort study. Spine 2017;42:556–64.
    OpenUrl
  12. 12.↵
    1. Zhu S,
    2. Xu W,
    3. Luo Y,
    4. Zhao Y,
    5. Liu Y
    . Cervical spine involvement risk factors in rheumatoid arthritis: a meta-analysis. Int J Rheum Dis 2017;20:541–9.
    OpenUrl
  13. 13.↵
    1. Han MH,
    2. Ryu JI,
    3. Kim CH,
    4. Kim JM,
    5. Cheong JH,
    6. Bak KH,
    7. et al.
    Factors that predict risk of cervical instability in rheumatoid arthritis patients. Spine 2017;42:966–73.
    OpenUrl
  14. 14.↵
    1. Abozaid HS,
    2. El-din Hassan RA,
    3. Elmadany WA,
    4. Ismail MA,
    5. Elgendy DS,
    6. Elsayed SA,
    7. et al.
    Is it the age at disease onset or the disease radiological severity that affects cervical spine involvement in patients with rheumatoid arthritis? Clin Med Insights Arthritis Musculoskelet Disord 2018;11:1–7.
    OpenUrl
  15. 15.↵
    1. Kauppi M,
    2. Neva MH
    . Sensitivity of lateral view cervical spine radiographs taken in the neutral position in atlantoaxial subluxation in rheumatic diseases. Clin Rheumatol 1998;17:511–4.
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Laiho K,
    2. Soini I,
    3. Kautiainen H,
    4. Kauppi M
    . Can we rely on magnetic resonance imaging when evaluating unstable atlantoaxial subluxation? Ann Rheum Dis 2003;62:254–6.
    OpenUrlAbstract/FREE Full Text
  17. 17.↵
    1. Del Grande M,
    2. Del Grande F,
    3. Carrino J,
    4. Bingham CO 3rd,
    5. Louie GH
    . Cervical spine involvement early in the course of rheumatoid arthritis. Semin Arthritis Rheum 2014;43:738–44.
    OpenUrl
  18. 18.↵
    1. Leirisalo-Repo M,
    2. Kautiainen H,
    3. Laasonen L,
    4. Korpela M,
    5. Kauppi MJ,
    6. Kaipiainen-Seppanen O,
    7. et al;
    8. NEO-RACo Study Group
    . Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo study). Ann Rheum Dis 2013;72:851–7.
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    1. Rantalaiho V,
    2. Kautiainen H,
    3. Korpela M,
    4. Hannonen P,
    5. Kaipiainen-Seppänen O,
    6. Möttönen T,
    7. et al;
    8. NEO-RACo Study Group
    . Targeted treatment with a combination of traditional DMARDs produces excellent clinical and radiographic long-term outcomes in early rheumatoid arthritis regardless of initial infliximab. The 5-year follow–up results of a randomised clinical trial, the NEO-RACo trial. Ann Rheum Dis 2014;73:1954–61.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    1. Rantalaiho V,
    2. Sandstrom T,
    3. Koski J,
    4. Hannonen P,
    5. Mottonen T,
    6. Kaipiainen-Seppanen O,
    7. et al;
    8. NEO-RACo Study Group
    . Early targeted combination treatment with conventional synthetic disease-modifying antirheumatic drugs and long-term outcomes in rheumatoid arthritis: ten-year follow-up results of a randomized clinical trial. Arthritis Care Res 2018;71:1450–8.
    OpenUrl
  21. 21.↵
    1. Arnett FC,
    2. Edworthy SM,
    3. Bloch DA,
    4. McShane DJ,
    5. Fries JF,
    6. Cooper NS,
    7. et al.
    The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315–24.
    OpenUrlCrossRefPubMed
  22. 22.↵
    1. Kauppi M,
    2. Sakaguchi M,
    3. Konttinen YT,
    4. Hamalainen M
    . A new method of screening for vertical atlantoaxial dislocation. J Rheumatol 1990;17:167–72.
    OpenUrlPubMed
  23. 23.↵
    1. Winfield J,
    2. Cooke D,
    3. Brook AS,
    4. Corbett M
    . A prospective study of the radiological changes in the cervical spine in early rheumatoid disease. Ann Rheum Dis 1981;40:109–14.
    OpenUrlAbstract/FREE Full Text
  24. 24.↵
    1. Neva MH,
    2. Kaarela K,
    3. Kauppi M
    . Prevalence of radiological changes in the cervical spine--a cross sectional study after 20 years from presentation of rheumatoid arthritis. J Rheumatol 2000;27:90–3.
    OpenUrlPubMed
PreviousNext
Back to top

In this issue

The Journal of Rheumatology
Vol. 47, Issue 8
1 Aug 2020
  • Table of Contents
  • Table of Contents (PDF)
  • Index by Author
  • Editorial Board (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about The Journal of Rheumatology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Cervical Spine Involvement among Patients with Rheumatoid Arthritis Treated Actively with Treat-to-target Strategy: 10-year Results of the NEO-RACo Study
(Your Name) has forwarded a page to you from The Journal of Rheumatology
(Your Name) thought you would like to see this page from the The Journal of Rheumatology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Cervical Spine Involvement among Patients with Rheumatoid Arthritis Treated Actively with Treat-to-target Strategy: 10-year Results of the NEO-RACo Study
Tia Sandström, Vappu Rantalaiho, Timo Yli-Kerttula, Hannu Kautiainen, Timo Malmi, Anna Karjalainen, Tea Uusitalo, Heikki Julkunen, Oili Kaipiainen-Seppänen, Leena Paimela, Kari Puolakka, Toini Uutela, Timo Möttönen, Pekka Hannonen, Marjatta Leirisalo-Repo, Leena Laasonen, Markku Kauppi, for the NEO-RACo Study Group
The Journal of Rheumatology Aug 2020, 47 (8) 1160-1164; DOI: 10.3899/jrheum.190139

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

 Request Permissions

Share
Cervical Spine Involvement among Patients with Rheumatoid Arthritis Treated Actively with Treat-to-target Strategy: 10-year Results of the NEO-RACo Study
Tia Sandström, Vappu Rantalaiho, Timo Yli-Kerttula, Hannu Kautiainen, Timo Malmi, Anna Karjalainen, Tea Uusitalo, Heikki Julkunen, Oili Kaipiainen-Seppänen, Leena Paimela, Kari Puolakka, Toini Uutela, Timo Möttönen, Pekka Hannonen, Marjatta Leirisalo-Repo, Leena Laasonen, Markku Kauppi, for the NEO-RACo Study Group
The Journal of Rheumatology Aug 2020, 47 (8) 1160-1164; DOI: 10.3899/jrheum.190139
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Bookmark this article

Jump to section

  • Article
    • Abstract
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • Acknowledgment
    • Footnotes
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • References
  • PDF
  • eLetters

Keywords

RHEUMATOID ARTHRITIS
CERVICAL SPINE
TREATMENT
ATLANTOAXIAL SUBLUXATION
DISEASE-MODIFYING ANTIRHEUMATIC DRUG

Related Articles

Cited By...

More in this TOC Section

  • Risk Factors for Dementia in Patients With Incident Rheumatoid Arthritis: A Population-Based Cohort Study
  • Can Patients With Controlled Rheumatoid Arthritis Taper Methotrexate From Targeted Therapy and Sustain Remission? A Systematic Review and Metaanalysis
  • Physical Activity Associates With Lower Systemic Inflammatory Gene Expression in Rheumatoid Arthritis
Show more Rheumatoid Arthritis

Similar Articles

Keywords

  • rheumatoid arthritis
  • CERVICAL SPINE
  • treatment
  • ATLANTOAXIAL SUBLUXATION
  • disease-modifying antirheumatic drug

Content

  • First Release
  • Current
  • Archives
  • Collections
  • Audiovisual Rheum
  • COVID-19 and Rheumatology

Resources

  • Guide for Authors
  • Submit Manuscript
  • Author Payment
  • Reviewers
  • Advertisers
  • Classified Ads
  • Reprints and Translations
  • Permissions
  • Meetings
  • FAQ
  • Policies

Subscribers

  • Subscription Information
  • Purchase Subscription
  • Your Account
  • Terms and Conditions

More

  • About Us
  • Contact Us
  • My Alerts
  • My Folders
  • Privacy/GDPR Policy
  • RSS Feeds
The Journal of Rheumatology
The content of this site is intended for health care professionals.
Copyright © 2022 by The Journal of Rheumatology Publishing Co. Ltd.
Print ISSN: 0315-162X; Online ISSN: 1499-2752
Powered by HighWire