Remission induction therapy with methotrexate and prednisone in patients with early rheumatoid and undifferentiated arthritis (the IMPROVED study).

AIM: Classifying more patients as rheumatoid arthritis (RA) (2010 American College of Rheumatology/European League Against Rheumatism criteria for RA) may improve treatment outcomes but may cause overtreatment in daily practice. The authors determined the efficacy of initial methotrexate (MTX) plus prednisone treatment in patients with 1987 or 2010 classified RA and undifferentiated arthritis (UA). METHOD: 610 recent onset RA or UA patients started with MTX 25 mg/week and prednisone 60 mg/day tapered to 7.5 mg/day in 7 weeks. Percentage remissions after 4 months were compared between RA (1987 or 2010 criteria) and UA. Predictors for remission were identified. RESULTS: With the 2010 criteria, 19% more patients were classified as RA than with the 1987 criteria, but similar remission rates were achieved: 291/479 (61%) 2010 classified RA and 211/264 (58%) 1987 classified RA patients (p=0.52), and 79/122 (65%) UA patients (p=0.46). Anticitrullinated protein antibodies (ACPA) positive RA patients achieved more remission (66%) than ACPA negative RA patients (51%, p=0.001), but also had a lower mean baseline Disease Activity Score (DAS) (3.2 vs 3.6, p<0.001). Independent predictors for remission were male sex, low joint counts, DAS and Health Assessment Questionnaire, low body mass index and ACPA positivity. CONCLUSION: Initial treatment with MTX and a tapered high dose of prednisone results in similarly high remission percentages after 4 months (about 60%) in RA patients, regardless of fulfilling the 1987 or 2010 criteria, and in UA patients. Independent predictors indicate that initiating treatment while disease activity is relatively low results in more remission.

Survival, comorbidities and joint damage 11 years after the COBRA combination therapy trial in early rheumatoid arthritis.

BACKGROUND: COBRA (for 'COmbinatie therapie Bij Rheumatoide Artritis') combination therapy is effective for the treatment of rheumatoid arthritis (RA), but long-term safety is unknown. This study evaluates survival, comorbidities and joint damage in the original COBRA trial cohort. METHODS: In the COBRA trial, 155 patients with early RA were treated with sulfasalazine (SSZ) monotherapy (SSZ group) or a combination of step-down prednisolone, methotrexate (MTX) and SSZ (COBRA group). The current 11-year follow-up study of the COBRA trial invited all original patients and performed protocollised scrutiny of clinical records, questionnaires, physical examination, laboratory and imaging tests. RESULTS: In all, 152 out of 155 patients yielded at least partial data. After a mean of 11 years follow-up, 18 (12%) patients had died, 6 COBRA patients and 12 SSZ patients, HR 0.57 (95% CI 0.21 to 1.52). Treatment for hypertension was significantly more prevalent in the COBRA group (p=0.02) with similar trends for diabetes and cataract. Conversely, hypercholesterolaemia, cancer and infection showed a trend in favour of COBRA. Other comorbidities such as cardiovascular disease and fractures appeared in similar frequency. Radiographic findings suggest as a minimum sustained benefit for COBRA therapy, that is, difference in joint damage but similar subsequent progression rates after 5 years. Imputation to compensate for selective dropout suggests increasing benefit for COBRA, that is, difference in yearly progression rates similar to that seen in the first 5 years of follow-up. CONCLUSIONS: After 11 years, initial COBRA combination therapy resulted in numerically lower mortality and similar prevalence of comorbidity compared with initial SSZ monotherapy. In addition, lower progression of joint damage suggests long-term disease modification.

Sick leave and work disability in patients with early arthritis.

We studied the occurrence of sick leave and work disability, the presence of workplace adaptations and the usage of professional guidance related to working problems in patients with early arthritis. Inclusion criteria were arthritis symptoms of less than 2 years duration and a paid job at the time of diagnosis. Assessments were done in connection with an early arthritis clinic (EAC) at entry into the cohort and 12 months thereafter by means of a questionnaire comprising questions on sick leave (absenteeism from work reported to the employer), work disability (receiving a full or partial work disability pension), unemployment, work adaptations and professional guidance related to working problems. Fifty-seven of the 69 participants (83%) had an arthritis symptom duration of <6 months. The number of patients with sick leave due to arthritis in the past 12 months decreased from 28 (41%) at study entry to 18 (26%) after 12 months of follow-up. The number of patients receiving a work disability pension increased from 5 (7%) at study entry to 13 (19%) after 12 months of follow-up (10 partial and 3 full). Sick leave in the 12 months before study entry appeared to be the most important predictor of the institution or increase in a work disability pension (odds ratio, 16.1; 95%CI, 1.8-142.8). Between study entry and follow-up, the number of patients with workplace adaptations increased from 20 (29%) to 28 (42%), whereas the number of patients receiving vocational guidance decreased from 48 (70%) to 36 (52%). In patients with early arthritis and a paid job, arthritis-related sick leave was common and occurred in part before patients entered the EAC and a diagnosis was made. About 20% of the patients became permanently work disabled, with partial work disability being more common than full work disability. Considerable proportions of patients received workplace adaptations and professional guidance with working problems.

Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To determine whether patients with undifferentiated arthritis (UA; inflammatory, nontraumatic arthritis that cannot be diagnosed using current classification criteria) benefit from treatment with methotrexate (MTX). METHODS: The PRObable rheumatoid arthritis: Methotrexate versus Placebo Treatment (PROMPT) study was a double-blind, placebo-controlled, randomized, multicenter trial involving 110 patients with UA who fulfilled the American College of Rheumatology (ACR) 1958 criteria for probable RA. Treatment started with MTX (15 mg/week) or placebo tablets, and every 3 months the dosage was increased if the Disease Activity Score was >2.4. After 12 months, the study medication was tapered and discontinued. Patients were followed up for 30 months. When a patient fulfilled the ACR criteria for RA (primary end point), the study medication was changed to MTX. Joint damage was scored on radiographs of the hands and feet. RESULTS: In 22 of the 55 patients (40%) in the MTX group, UA progressed to RA compared with 29 of 55 patients (53%) in the placebo group. However, in the MTX group, patients fulfilled the ACR criteria for RA at a later time point than in the placebo group (P = 0.04), and fewer patients showed radiographic progression over 18 months (P = 0.046). CONCLUSION: This study provides evidence for the efficacy of MTX treatment in postponing the diagnosis of RA, as defined by the ACR 1987 criteria, and retarding radiographic joint damage in UA patients.

Randomized comparison of a multidisciplinary job-retention vocational rehabilitation program with usual outpatient care in patients with chronic arthritis at risk for job loss.

OBJECTIVE: Work disability is a major consequence of inflammatory rheumatic conditions. Evidence regarding the effectiveness of interventions aimed at the prevention or reduction of work disability in rheumatic diseases is limited. We conducted a randomized controlled trial to investigate the effectiveness of a multidisciplinary job-retention vocational rehabilitation (VR) program in patients with a rheumatic condition who were at risk for job loss. METHODS: A total of 140 patients with a chronic rheumatic condition were randomly assigned to either a multidisciplinary job-retention VR program (n = 74) or usual outpatient care (UC) (n = 66). Patients in the VR group were assessed and guided by a multidisciplinary team, whereas patients in the UC group received care as initiated by their rheumatologist, supplemented with written information. The main outcome measure was the occurrence of job loss (complete work disability or unemployment); additional outcome measures included job satisfaction, pain, functional status, emotional status, and quality of life. RESULTS: There was no difference between the 2 groups regarding the proportion of patients having lost their job at any time point, with 24% and 23% of the patients in the VR and UC groups, respectively, having lost their job after 24 months. Over the total period of 24 months, patients in the VR group had a significantly greater improvement of the fatigue visual analog scale and of emotional status (all P values < 0.05). CONCLUSION: A job-retention VR program did not reduce the risk of job loss but improved fatigue and mental health in patients with chronic rheumatic diseases at risk for job loss.

COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention.

OBJECTIVE: The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial demonstrated that step-down combination therapy with prednisolone, methotrexate, and sulfasalazine (SSZ) was superior to SSZ monotherapy for suppressing disease activity and radiologic progression of rheumatoid arthritis (RA). The current study was conducted to investigate whether the benefits of COBRA therapy were sustained over time, and to determine which baseline factors could predict outcome. METHODS: All patients had participated in the 56-week COBRA trial. During followup, they were seen by their own rheumatologists and were also assessed regularly by study nurses; no treatment protocol was specified. Disease activity, radiologic damage, and functional ability were the primary outcome domains. Two independent assessors scored radiographs in sequence according to the Sharp/van der Heijde method. Outcomes were analyzed by generalized estimating equations on the basis of intent-to-treat, starting with data obtained at the last visit of the COBRA trial (56 weeks after baseline). RESULTS: At the beginning of followup, patients in the COBRA group had a significantly lower mean time-averaged 28-joint disease activity score (DAS28) and a significantly lower median radiologic damage (Sharp) score compared with those in the SSZ monotherapy group. The functional ability score (Health Assessment Questionnaire [HAQ]) was similar in both groups. During the 4-5 year followup period, the time-averaged DAS28 decreased 0.17 points per year in the SSZ group and 0.07 in the COBRA group. The Sharp progression rate was 8.6 points per year in the SSZ group and 5.6 in the COBRA group. After adjustment for differences in treatment and disease activity during followup, the between-group difference in the rate of radiologic progression was 3.7 points per year. The HAQ score did not change significantly over time. Independent baseline predictors of radiologic progression over time (apart from treatment allocation) were rheumatoid factor positivity, Sharp score, and DAS28. CONCLUSION: An initial 6-month cycle of intensive combination treatment that includes high-dose corticosteroids results in sustained suppression of the rate of radiologic progression in patients with early RA, independent of subsequent antirheumatic therapy.