A two-step treatment strategy trial in patients with early arthritis aimed at achieving remission: the IMPROVED study.

OBJECTIVES: To assess which treatment strategy is most effective in inducing remission in early (rheumatoid) arthritis. METHODS: 610 patients with early rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) started treatment with methotrexate (MTX) and a tapered high dose of prednisone. Patients in early remission (Disease Activity Score <1.6 after 4 months) tapered prednisone to zero and those with persistent remission after 8 months, tapered and stopped MTX. Patients not in early remission were randomised to receive either MTX plus hydroxychloroquine plus sulfasalazine plus low-dose prednisone (arm 1) or to MTX plus adalimumab (ADA) (arm 2). If remission was present after 8 months both arms tapered to MTX monotherapy; if not, arm 1 changed to MTX plus ADA and arm 2 increased the dose of ADA. Remission rates and functional and radiological outcomes were compared between arms and between patients with RA and those with UA. RESULTS: 375/610 (61%) patients achieved early remission. After 1 year 68% of those were in remission and 32% in drug-free remission. Of the randomised patients, 25% in arm 1 and 41% in arm 2 achieved remission at year 1 (p<0.01). Outcomes were comparable between patients with RA and those with UA. CONCLUSIONS: Initial MTX and prednisone resulted in early remission in 61% of patients with early (rheumatoid) arthritis. Of those, 68% were in remission and 32% were in drug-free remission after 1 year. In patients not in early remission, earlier introduction of ADA resulted in more remission at year 1 than first treating with disease-modifying antirheumatic drug combination therapy plus prednisone.

Changes in hand bone mineral density and the association with the level of disease activity in patients with rheumatoid arthritis: bone mineral density measurements in a multicenter randomized clinical trial.

OBJECTIVE: To determine if metacarpal bone mineral density (mBMD) gain occurs in patients with rheumatoid arthritis (RA). If mBMD loss is driven by inflammation, we expect to find mBMD gain in patients who are in remission. METHODS: mBMD was measured by digital x-ray radiogrammetry in consecutive radiographs of 145 patients with RA with either continuous high disease activity (HDA; Disease Activity Score [DAS] >2.4), low disease activity (LDA; 1.6 ≥ DAS ≤ 2.4), or continuous clinical remission (CR; DAS <1.6) during a 1-year observation period. The association of mBMD changes with disease activity was investigated with multinomial regression analysis. Next, clinical variables associated with mBMD gain were identified. RESULTS: Mean change in mBMD in CR patients was -0.03%, compared to -3.13% and -2.03% in HDA and LDA patients, respectively (overall, P < 0.001). Of the patients in CR, 32% had mBMD loss (less than or equal to -4.6 mg/cm2/year), compared to 62% and 66% of the patients with HDA or LDA, respectively, whereas 26% of the patients in CR had mBMD gain (≥4.6 mg/cm2/year), compared to 2% of the patients with HDA and 5% of the patients with LDA. Patients in CR had a higher chance of having mBMD gain, compared with LDA and HDA (relative risk [RR] 14.9, 95% confidence interval [95% CI] 3.0-18.7 and RR 4.7, 95% CI 1.2-6.3, respectively). CR, hormone replacement therapy, and lower age were significant independent predictors of mBMD gain. CONCLUSION: In RA, mBMD gain occurs primarily in patients in continuous (≥1 year) CR and rarely in patients with continuous HDA or LDA. This suggests that mBMD loss is driven by inflammation.

DAS-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis.

OBJECTIVES: To compare the efficacy of Disease Activity Score (DAS)-driven therapy and routine care in patients with recent-onset rheumatoid arthritis. METHODS: Patients with recent-onset rheumatoid arthritis receiving traditional antirheumatic therapy from either the BeSt study, a randomised controlled trial comparing different treatment strategies (group A), or two Early Arthritis Clinics (group B) were included. In group A, systematic DAS-driven treatment adjustments aimed to achieve low disease activity (DAS < or =2.4). In group B, treatment was left to the discretion of the treating doctor. Functional ability (Health Assessment Questionnaire (HAQ)), Disease Activity Score in 28 joints (DAS28) and Sharp/van der Heijde radiographic score (SHS) were evaluated. RESULTS: At baseline, patients in group A (n = 234) and group B (n = 201) had comparable demographic characteristics and a mean HAQ of 1.4. Group A had a longer median disease duration than group B (0.5 vs 0.4 years, p = 0.016), a higher mean DAS28 (6.1 vs 5.7, p<0.001), more rheumatoid factor-positive patients (66% vs 42%, p<0.001) and more patients with erosions (71% vs 53%, p<0.001). After 1 year, the HAQ improvement was 0.7 vs 0.5 (p = 0.029), and the percentage in remission (DAS28 <2.6) 31% vs 18% (p<0.005) in groups A and B, respectively. In group A, the median SHS progression was 2.0 (expected progression 7.0), in group B, the SHS progression was 1.0 (expected progression 4.4). CONCLUSIONS: In patients with recent-onset rheumatoid arthritis receiving traditional treatment, systematic DAS-driven therapy results in significantly better clinical improvement and possibly improves the suppression of joint damage progression.

Effectiveness of systematic monitoring of rheumatoid arthritis disease activity in daily practice: a multicentre, cluster randomised controlled trial.

OBJECTIVE: To test the efficacy of standardised monitoring using the disease activity index DAS28 versus usual care on disease modifying antirheumatic drug (DMARD) prescription and disease activity in rheumatoid arthritis. METHODS: A 24 week cluster randomised trial. Rheumatology outpatient centres were randomised to systematic monitoring of disease activity using the DAS28 (12 centres, 205 patients) or usual care (12 centres, 179 patients). The aim for the DAS group was to reach a DAS28 score of < or =3.2 by changes in DMARD treatment, at the discretion of the rheumatologist and the patient. RESULTS: At baseline, disease activity was the same in both groups, with an overall mean (SD) DAS28 of 4.5 (1.2); 13% of the patients had a DAS28 of < or =3.2. At 24 weeks, 31% of patients in the DAS group had a DAS28 < or =3.2, while in the usual care centres this was 16% (p = 0.028). DMARDs were changed on average in 18% of visits in the DAS centres; in the 12 usual care centres they were changed on 8% of the visits (p = 0.013). The doses of methotrexate, sulfasalazine, and corticosteroids appeared to be higher in the DAS centres than in the usual care centres, but the differences were not significant. CONCLUSIONS: In daily practice, systematic monitoring of disease activity in rheumatoid arthritis may lead to more changes in DMARD treatment, resulting in a larger number of patients with low disease activity.

Sarcoid arthritis: clinical characteristics, diagnostic aspects, and risk factors.

OBJECTIVES: (a) To describe the clinical characteristics of acute sarcoid arthritis and the diagnostic value of its presenting clinical features; (b) to evaluate whether disease onset is seasonal; and (c) to evaluate whether smoking behaviour or the presence of HLA class II alleles is a risk factor for the disease. METHODS: 579 consecutive patients with recent onset arthritis who had been newly referred to a rheumatology outpatient clinic were included in a prospective cohort study. The presenting clinical features, the smoking behaviour, and the results of HLA-DQ and HLA-DR DNA typing of 55 patients with sarcoid arthritis, 524 patients with other arthritides of recent onset, and samples of the normal population were compared. RESULTS: In all cases the disease showed a self limiting arthritis and overall good prognosis. The diagnostic ability of a combination of four clinical features--symmetrical ankle arthritis, symptoms of less than two months, age below 40 years, and erythema nodosum--was exceptionally high. When test positivity is defined as the presence of at least three of four criteria the set rendered a sensitivity of 93%, a specificity of 99%, a positive predictive value of 75%, and a negative predictive value of 99.7%. The disease clustered in the months March-July. The disease was negatively associated with smoking (odds ratio (OR) 0.09; 95% confidence interval (95% CI) 0.02 to 0.37) and positively associated with the presence of the DQ2 (DQB1*0201)-DR3 (DRB1*0301) haplotype (OR 12.33; 95% CI 5.97 to 25.48). CONCLUSION: The disease entity acute sarcoid arthritis has highly diagnostic clinical features. The seasonal clustering, the protective effect of smoking, and the association with specific HLA class II antigens support the hypothesis that it results from exposure of susceptible hosts to environmental agents through the lungs.

Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies.

PURPOSE: To compare the effect of delayed and early treatment strategies on disease outcome in patients with rheumatoid arthritis. SUBJECTS AND METHODS: Between 1993 and 1995, 109 patients diagnosed with probable or definite rheumatoid arthritis of recent onset were initially treated with analgesics; if they had persistent active disease, they were treated subsequently with the disease-modifying drugs chloroquine or salazopyrine (delayed treatment). Between 1996 and 1998, similar patients (n = 97) were promptly treated with either chloroquine or salazopyrine (early treatment). RESULTS: The median lag to the initiation of disease-modifying treatment was 15 days in the early treatment group and 123 days in the delayed treatment group. There was less radiologic joint damage after 2 years in the early treatment group (median Sharp score, 3.5; 95% confidence interval [CI]: 1 to 7) compared with the delayed treatment group (median Sharp score, 10; 95% CI: 5 to 15; P <0.05). The median area under the curve of the 2-year disease activity score was lower in the early treatment group (64 units; 95% CI: 59 to 69 units) compared with the delayed treatment group (73 units; 95% CI: 69 to 77 units; P = 0.002). CONCLUSION: In this nonrandomized comparison, early introduction of disease-modifying antirheumatic drugs was associated with a better disease outcome after 2 years.

The diagnostic value of streptococcal serology in early arthritis: a prospective cohort study.

OBJECTIVE: To evaluate the diagnostic value of streptococcal serology in adult early arthritis patients in discriminating between post-streptococcal reactive arthritis (PSRA) and arthritis with other causes. METHODS: The antistreptolysin-O (ASO) and anti-DNase B tests were performed at baseline in 366 consecutive, newly referred early arthritis patients. After 1 yr of follow-up the patients were classified according to international classification criteria and were evaluated for the presence of persistent arthritis. The outcome measures were the predictive value of streptococcal serology for the diagnosis of PSRA and the ability of this serology to discriminate at the first visit between the self-limiting and persistent forms of arthritis. RESULTS: With a positive serological result, the probability of having PSRA increased from 2 to 9%, whereas the probabilities of having rheumatoid arthritis or undifferentiated arthritis continued to be high (23 and 29%). The serological tests did not discriminate between the self-limiting and persistent forms of arthritis. The major Jones criteria apart from arthritis were not observed. CONCLUSION: Streptococcal serology has no diagnostic value in adult early arthritis patients in whom major Jones criteria other than arthritis are not present.

Diagnosis and course of early-onset arthritis: results of a special early arthritis clinic compared to routine patient care.

OBJECTIVE: Early arthritis patients referred to an Early Arthritis Clinic (EAC) (n = 233) were compared to 241 patients from the routine out-patient clinic with respect to lag time between the onset of symptoms and the visit to the rheumatologist, clinical presentation and the consistency of the diagnosis after 1 yr. RESULTS: The reduction in median lag time for the EAC patients was at least 3 months. An insidious onset of symptoms was found more often in the rheumatoid arthritis (RA) patients in the routine clinic. In 70% of all cases, a diagnosis could be made after 2 weeks and, if the clinical diagnosis was definite RA, this hardly changed during the following year. Early erosions were seen in 25% of RA patients and were associated with a positive rheumatoid factor (OR 2.08, 95% CI 0.95 4.59). CONCLUSION: An early diagnosis of RA at the EAC is possible and reliable; the high frequency of erosions illustrates the need for early treatment.

Human parvovirus B19 infection is not followed by inflammatory joint disease during long term follow-up. A retrospective study of 54 patients.

OBJECTIVE: To investigate whether recent human parvovirus B19 (B19) infection provokes inflammatory arthritis, we assessed the outcome of 54 patients with recent B19 infection who were referred to the Department of Rheumatology. METHODS: Consecutive patients referred between 1985 and 1995 and found to have a recent B19 infection were studied retrospectively by sending a questionnaire and, if necessary, by physical examination. RESULTS: In the acute phase of B19 infection, all patients had arthralgia and many also complained of myalgia and malaise. Arthritis was found in 61% of the patients, skin rash in 72% and fever in 64%. Except for the arthralgia and malaise, most of the symptoms resolved rapidly. After a mean followup of 5 years (SD 2.9 yrs.) none of the patients reported persistence of joint swelling or restricted motion. CONCLUSION: None of the 54 patients with recent B19 infection developed chronic arthritis.

[Diagnosis and course of early arthritis; study in a specialized clinic for early arthritis]. / Diagnose en verloop van vroege artritis; onderzoek op een gespecialiseerde polikliniek voor vroege artritis.

OBJECTIVE: To investigate the occurrence, diagnosis and course of all new inflammatory arthropathies seen in a special Early Arthritis Clinic (EAC). DESIGN: Prospective cohort study. SETTING: Academic Medical Hospital, Leiden, The Netherlands. METHODS: An Early Arthritis Clinic (EAC) was started in the outpatient clinic of rheumatology of Leiden University Hospital for diagnostic work-up according to protocol of patients with recent-onset arthritis. Inclusion criteria were: active arthritis with onset < 2 years without traumatic aetiology and no referral for a second opinion. RESULTS: In the first 18 months 276 patients were sent to the EAC, 212 met the inclusion criteria. After 2 weeks the following diagnoses were made: rheumatoid arthritis (RA) (58; 28%), psoriatic arthritis (8; 4%), reactive arthritis (11; 5%) sarcoidosis (9; 4%), crystal arthritis (30; 14%), osteoarthritis (8; 4%), other diagnosis (18; 8%). The remaining 70 patients (33%) were classified as arthritis e causa ignota (e.c.i.). After follow-up, the first diagnoses changed in 27 (12%) patients, of whom 20 patients originally had had the diagnosis of arthritis e.c.i. Persistent arthritis was found in 90% of RA and in 35% of arthritis e.c.i. Other forms of arthritis seldom showed persistent activity. CONCLUSION: In the EAC, RA, arthritis e.c.i. and crystal arthritis were seen most often. Almost all RA patients showed persistent arthritis, as against only a third of those with arthritis e.c.i. Because of the early diagnosis treatment could start early in patients with joint disease entailing irreversible joint destruction.

Recruitment of patients with early rheumatoid arthritis -- the Netherlands experience.

We wished to evaluate whether early arthritis clinics (EAC) contribute to the shortening of time between the onset of complaints and the moment that adequate therapy is started in patients with arthritis. We evaluated 212 patients with arthritis referred in 1993 to an EAC. A definite diagnosis could be made in 68% of the patients 2 weeks after referral. Arthritis persisted in a large majority of patients with rheumatoid arthritis and the time between disease onset and initiation of therapy could be reduced to +/-3 months. EAC are therefore helpful in achieving early effective treatment of arthritis.

Technetium-99m labelled human immunoglobulin scintigraphy predicts rheumatoid arthritis in patients with arthralgia.

The ability of 99mTc-IgG scintigraphy to predict the development of rheumatoid arthritis (RA) in 47 patients with arthralgia was investigated. 99mTc-IgG scintigraphy and the serum test for rheumatoid factor (RF), measured at the beginning of a year long study, were compared for their ability to predict RA. During the study 8 patients developed RA. The specificity and positive predictive values of RF in predicting RA were 79% and 50% respectively; and for 99mTc-IgG scintigraphy 97% and 88%. The sensitivity and negative predictive values of RF were 100% and of 99mTc-IgG-scintigraphy 88% and 97% respectively. In conclusion, 99mTc-IgG scintigraphy has additional value to RF with respect to the prediction of the development of RA in patients with arthralgia.

Prevention of group B streptococci transmission during delivery by vaginal application of chlorhexidine gel.

In a prospective study in 227 parturients, carriership of group B streptococci was established to be 25%. In carriers, transmission of streptococci to the newborn occurred in 50%. 10 ml of a chlorhexidine gel containing hydroxypropylmethylcellulose was introduced into the vagina during labor in 17 parturients, who were known to be carriers of group B streptococci from the first trimester of pregnancy. In none of the newborns from these mothers colonization by group B streptococci did occur. Vaginal application of chlorhexidine may prevent transmission of group B streptococci, and serve as an alternative to intrapartum prophylaxis using antibiotics. A large multicenter randomized controlled study should be performed to confirm this hypothesis.