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

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 (NCT00908089). 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.

High burden of adverse events is associated with reduced remission rates in early rheumatoid arthritis.

Adverse events (AEs) are common during disease-modifying antirheumatic drug (DMARD) treatment, but their influence on treatment results is unclear. We studied AEs in relation to disease activity in early rheumatoid arthritis (RA). Ninety-nine patients started intensive treatment with three conventional synthetic DMARDs (csDMARDs) and oral prednisolone, and were randomized to a 6-month induction treatment with infliximab or placebo. All AEs during the first 12 months of treatment were recorded. We scored each AE based on severity (scale 1-4) and defined the burden of AEs as the sum of these scores. Patients were divided into tertiles according to the burden of AEs. As outcomes, we assessed 28-joint disease activity score (DAS28) levels and remission rates at 12 and 24 months. Three hundred thirty-one AEs in 99 patients were reported, and 27 (8%) were categorized as severe or serious. Mean burden of AEs per patient was 5.4 ± 4.3. Seventy-nine AEs (24%) led to temporary (n = 52) or permanent (n = 27) csDMARD discontinuation. Of discontinuations, 1, 21, and 57 were detected in the first, second, and third tertiles, respectively. DAS28 remission rates decreased across tertiles at 12 months (94, 94, and 76%; p for linearity 0.029) and at 24 months (90, 86, and 70%; p for linearity 0.021). Mean DAS28 levels increased across tertiles at 12 months (1.5 ± 1.0, 1.7 ± 0.9, and 1.9 ± 1.2; p for linearity 0.021) and at 24 months (1.4 ± 0.8, 1.6 ± 1.0, and 1.9 ± 1.1; p for linearity 0.007). High burden of AEs is associated with higher disease activity and lower likelihood of remission in early RA.

Intra-articular glucocorticoid injections should not be neglected in the remission targeted treatment of early rheumatoid arthritis: a post hoc analysis from the NEO-RACo trial.

OBJECTIVES: To study the effects of neglecting intra-articular glucocorticoid injections (IAGCIs) into swollen joints in early rheumatoid arthritis (RA). METHODS: Ninety-nine patients with early, DMARD naive RA were treated, aiming at remission, with methotrexate, sulfasalazine, hydroxychloroquine, low-dose oral prednisolone and, when needed, IAGCIs for 2 years, and randomised to receive infliximab or placebo from weeks 4 to 26. During each of the 15 study visits, patients were scored retrospectively 0.2-0.4 points (depending on the number of non-injected joints) if IAGCIs to all swollen joints were not given. Patients were divided into tertiles by their cumulative scores for neglected injections (CSNI) over 24 months. 28-joint disease activity score (DAS28) area under the curve (AUC) between 0-24 months, remission rates, changes in quality of life, and radiological changes during the follow-up were assessed. Trends across tertiles of CSNI were tested with generalised linear models. RESULTS: Higher CSNI was associated with lower strict remission rates (p=0.005), and lower quality of life (p=0.004) at 24 months, and higher DAS28 AUC (p<0.001) during the follow-up. At 24 months, DAS28 remission rates were 90%, 93% and 76% (p=0.081), and strict remission rates were 74%, 77% and 39% by tertiles of CSNI. No significant differences were observed in radiological progression (p=0.089). IAGCIs were well tolerated. CONCLUSIONS: Neglecting IAGCIs into swollen joints is associated with lower remission rates, higher disease activity, and lower quality of life. Hence, IAGCIs should be used as an integral part of the targeted treatment of early RA.

Failure in longterm treatment is rare in actively treated patients with rheumatoid arthritis, but may be predicted by high health assessment score at baseline and by residual disease activity at 3 and 6 months: the 5-year followup results of the randomized clinical NEO-RACo trial.

OBJECTIVE: With modern initial aggressive combination treatments with synthetic disease-modifying antirheumatic drugs (sDMARD), most patients with rheumatoid arthritis (RA) achieve remission, have marginal radiographic progression, and sustain normal function. Here we aim to identify the patients failing these targets even after aggressive treatment. METHODS: Ninety-nine patients with early, active RA were treated with a combination of 3 sDMARD and prednisolone (PRD), and either infliximab or placebo infusions during the first 6 months, aiming at strict remission. After 24 months, the treatments became unrestricted. At 60 months, 4 evident clinical features of treatment failure were defined: area under curve (AUC) between 6-60 months for disease activity score assessing 28 joints > 2.6; AUC 6-60 for health assessment questionnaire > 0.5; progression in total Sharp/van der Heijde score 0-60 months > 3 units; and need of PRD or biologic DMARD treatment at 60 months. RESULTS: A total of 93 patients were followed up for 60 months. Of them, 45 had no features of treatment failure, 30 had 1, 10 had 2, 7 had 3, and 1 patient had all 4 features. Having 2-4 features of treatment failure at 5 years was predicted by the health assessment score at baseline, and by even low residual disease activity at 3 and 6 months. CONCLUSIONS: Only 20% of the patients with RA treated early with combination sDMARD and PRD have more than 1 clinical feature of treatment failure at 60 months. Residual clinical disease activity at 3-6 months was the most important predictor for identifying these patients. The study was registered at www.clintrials.gov (NCT00908089).

Work disability in Finnish patients with rheumatoid arthritis: a 15-year follow-up.

OBJECTIVES: To investigate long-term work disability of patients with early rheumatoid arthritis (RA) and to examine impact of early disease activity and radiological progression on the loss of final work capacity. METHODS: Work disability due to RA was studied over 15 years in 86 Finnish patients with early RA and available for the labour force at study entry. RA-related retirement was studied in relation to early disease activity defined as the 28-joint disease activity score area under curve (DAS28 AUC) during the first 12 months and the impact of early radiological progression from the baseline to year 1. RESULTS: The RA-related retirement rate was 7% after the first year, 11% after 2 years, 19% after 5 years, 33% after 10 years and 39% after 15 years. Of the patients with low disease activity (DAS28 AUC ≤3.2) none were retired during the first 3 years. The retirement rate was also lower in subsequent years (10% after 5 years, 14% after 10 years, and 27% after 15 years) among these patients compared to those with DAS28 AUC >3.2 (28%, 55%, and 64%, respectively). A similar trend was evident among patients with no radiological progression (≤1 unit increase in Larsen score) and those with >1 Larsen unit of progression during the first year of RA. CONCLUSIONS: Our study suggests that low disease activity and halting of radiological progression during the first year of the disease improve possibilities to maintain work capacity in RA during the subsequent 15 years.

Double-blind, randomized, placebo-controlled study of three-month treatment with the combination of ofloxacin and roxithromycin in recent-onset reactive arthritis.

In a randomized, double-blind, placebo-controlled trial, 56 patients with recent-onset ReA [enteroarthritis, n = 47 (84%); uroarthritis, n = 9 (16%)] were randomly assigned to receive 200 mg ofloxacin and 150 mg roxithromycin twice daily (Combi, n = 26) or placebo (n = 30) for 3 months. Patients were assessed at entry, at 2 weeks, and at 1, 2, 3, 4, 5, and 6 months. The primary outcome measure was recovery from arthritis at 6 months, and secondary outcome measures were swollen and tender joint counts, Ritchie index, serum CRP level, erythrocyte sedimentation rate, and joint pain on a visual analogue scale at 6 months. After 6 months, 20 patients [77% (95% CI 56-91)] in Combi and 20 patients [67% (95% CI 47-83)] in placebo group had recovered from arthritis (p = 0.55), and all clinical and laboratory variables showed improvement with no statistically significant difference between groups. Adverse events were reported by 62% of the patients in the Combi versus 40% in the placebo group. In conclusion, outcome of ReA was good in both treatment groups. Three-month treatment with the combination of ofloxacin and roxithromycin had no advantage over placebo in patients with recent-onset ReA.

[Imaging of inflammatory back pain]. / Tulehduksellisen selkäkivun kuvantamis- diagnostiikka.

We recommend magnetic resonance imaging of the sacroiliac joints as the first line imaging method in suspected inflammatory back disorder. Plain X-ray can be taken from those over 35 years of age. A nonconclusive finding in plain X-ray should be verified by MR imaging. For the present, diagnostic criteria for spondylarthritis do not take into account spinal changes. Typical spinal findings can, however, be helpful in making treatment decisions. In case the spinal region MR imaging should be utilized if possible, because radiography is particularly insensitive for thoracic spine. After a confirmed diagnosis, the inflammatory nature of the condition can usually be assessed clinically.

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).

OBJECTIVE: Early treatment of patients with rheumatoid arthritis (RA) with combination treatment starting with methotrexate, sulfasalazine, hydroxychloroquine and prednisolone (FIN-RACo strategy) is superior to monotherapy. A study was undertaken to determine whether infliximab (INFL) added to intensified FIN-RACo treatment for the initial 6 months improves the 2-year outcome. METHODS: 99 patients with early untreated active RA were enrolled in an investigator-initiated, randomised, double-blind, multicentre, parallel-group trial. Primary outcomes were remission and radiological changes at 2 years. All patients started with FIN-RACo. In addition, they were randomised to receive INFL or placebo (Pla) from weeks 4 to 26. RESULTS: At 24 months, 66% and 53%, respectively, of the patients in the FIN-RACo+INFL and FIN-RACo+Pla groups were in remission according to the modified American College of Rheumatology (ACR) criteria (p=0.19), 26% and 10% were in sustained modified ACR remission (p=0.042) and 82% in both groups were in remission by 28-joint disease activity score (not significant). Mean changes in the total Sharp-van der Heijde score were 0.2 and 1.4, respectively (p=0.0058). CONCLUSIONS: Most patients with early active RA achieve clinical remission and develop negligible joint damage with the intensified FIN-RACo regimen. Adding INFL for the first 6 months delays radiological progression.

Causes of death in patients with rheumatoid arthritis from 1971 to 1991 with special reference to autopsy.

Rheumatoid arthritis (RA) patients have premature mortality, mostly attributed to cardiovascular diseases (CVDs). We studied causes of death (CoDs) and contribution of autopsy to them in RA patients treated at a single hospital responsible for primary to tertiary RA treatment in Helsinki. In 1971-1991, 960 RA patients died. The leading CoDs were CVDs, RA, and infections. Over 1971-1991, RA and renal deaths declined, but other CoDs showed no change. Autopsied patients died more frequently than nonautopsied of coronary heart disease (CHD) and gastrointestinal disorders, but less frequently of RA, renal, and endocrinologic diseases. Our finding of autopsied patients having CHD more frequently as a CoD may indicate that CHD, which may be asymptomatic in RA, may be overlooked during lifetime.

Amyloidosis is frequently undetected in patients with rheumatoid arthritis.

Prevalence of AA amyloid in rheumatoid arthritis (RA) is still unclear. The objective of this retrospective study was whether dedicated re-examination of autopsy tissues from RA patients increases the detection rate of amyloid compared to routine examination. Amyloid was re-examined in tissue samples and detection rate compared with original reports of 369 consecutively autopsied RA patients and 370 non-RA patients matched for sex, age, and year of autopsy between 1952 and 1991. Re-examination of 90% of the 739 cases showed doubling of the prevalence of amyloid compared with the original reports: from 18 to 30% in RA and from 2 to 4% in non-RA patients. In RA patients, cardiac amyloid was as frequent as renal amyloid. In RA patients with amyloid at re-examination, amyloidosis had been diagnosed before autopsy in 37%, and these patients had more inflammation and longer disease duration than RA patients without amyloid. Only 56% of RA patients with renal amyloid were known to have proteinuria. In conclusion, this autopsy study shows that amyloid in RA is a common finding which remains frequently undetected. In patients with active and long-lasting RA, a systematic search for amyloid may enable early diagnosis of amyloidosis, which will require effective suppression of inflammation.

Similar results with 21 Kudo and 21 Souter-Strathclyde total elbow arthroplasties in patients with rheumatoid arthritis.

INTRODUCTION: The results of different prostheses used for total elbow arthroplasty (TEA) in rheumatoid arthritis (RA) have been reported in only a few studies. Small differences in survival or function between implants have been reported. We retrospectively evaluated the results of 42 Souter-Strathclyde and Kudo TEAs. MATERIALS AND METHODS: Between 1988 and 1994, 21 consecutive patients with RA and severe elbow destruction underwent a Souter-Strathclyde TEA. Between 1994 and 1998, another group comprising 21 consecutive patients with RA with severe elbow destruction underwent a Kudo TEA. RESULTS: There were six revisions for the groups combined, including four aseptic loosenings, one fracture and one liner wear and metallosis. The 5-year survival for the Souter-Strathclyde and the Kudo were 85% (95% CI 69-100) and 95% (95% CI 85-100), respectively. The difference between the groups was not statistically significant as tested by the Cox regression analysis. The majority of the patients were free of pain at follow-up. More than half of the patients were able to perform only light housekeeping tasks and a considerable proportion even had difficulties in maintaining personal hygiene. The elbow range of motion improved only slightly after the operation. CONCLUSION: Both the Souter-Strathclyde and the Kudo TEAs provide good pain relief in the arthritic elbow leading to high patient satisfaction despite the residual disabilities. Only small differences in the results between the Souter-Strathclyde and the Kudo TEAs were found. More than half of the patients were able to perform only light housekeeping tasks and a considerable proportion even had difficulties in maintaining personal hygiene. The elbow range of motion improved only slightly after the operation.

The treatment of disc-herniation-induced sciatica with infliximab: one-year follow-up results of FIRST II, a randomized controlled trial.

STUDY DESIGN: A randomized controlled trial. OBJECTIVES: To evaluate the long-term efficacy of infliximab, a monoclonal antibody against tumor necrosis factor alpha (TNF-alpha), in patients with acute/subacute sciatica secondary to herniated disc. SUMMARY OF BACKGROUND DATA: The results of experimental studies and our open-label trial support the use of infliximab in sciatica. Here we report the 1-year results of a randomized controlled trial (FIRST II, Finnish Infliximab Related STudy) evaluating the efficacy and safety of a single infusion of infliximab for sciatic pain. METHODS: Inclusion criteria were unilateral sciatic pain with a disc herniation concordant with the symptoms and signs of radicular pain. Patients had to be candidates for discectomy. Criteria for discectomy included (in addition to a symptomatic disc herniation on MRI) neural entrapment (straight leg raising [SLR] < or =60 degrees ) with either a short-term (2-4 weeks) severe or long-term (4-12 weeks) moderate leg pain. Forty patients were allocated to a single intravenous infusion of either infliximab 5 mg/kg or placebo. Differences in the clinical examination parameters (straight leg raise [SLR], muscle strength, sensory defects, tendon reflexes), patient-reported symptoms (leg and back pain using a visual analog scale [VAS], Oswestry disability, quality-of-life [RAND-36]), sick leaves, number of discectomies, and adverse effects between the two treatment groups over the 1-year follow-up were compared using Mann-Whitney U test or Student's t test, repeated-measures analysis, or Cox proportional hazards model. Logistic regression was used to assess the predictors of good response. RESULTS: Sixty-seven percent of patients in the infliximab group reported no pain at 52 weeks compared with 63% in the control group (P = 0.72). Similar efficacy was observed between treatment groups for other outcomes. Eight patients in each group required surgery. Three nonserious adverse reactions were encountered in the infliximab group. The response (irrespective of the treatment) was significantly better with shorter symptom duration and less SLR restriction at baseline. Patients in the infliximab group appeared to especially benefit in cases of a L4-L5 (or L3-L4) herniation and if a Modic change was colocalized at the symptomatic level. CONCLUSIONS: Although the long-term results of this randomized trial do not support the use of infliximab compared with placebo for lumbar radicular pain in patients with disc herniation-induced sciatica, further study in a subgroup of patients with L4-L5 or L3-L4 herniations, especially in the presence of Modic changes, appears to be warranted.

The potential use of antibacterial peptide antibody indices in the diagnosis of rheumatoid arthritis and ankylosing spondylitis.

BACKGROUND: Both rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are potentially disabling arthritic disorders for which as yet no highly sensitive and reliable diagnostic laboratory markers are available. OBJECTIVE: The objective of this study was to evaluate the levels of antibodies against Proteus and Klebsiella antigenic peptides in an endeavor to develop diagnostic indices for the identification of patients with RA and AS, respectively. METHODS: Sera from 50 patients with RA, 34 patients with AS, and 38 healthy subjects were screened for antibodies against "ESRRAL" and "IRRET" synthetic amino acid peptides obtained from Proteus hemolysin and urease (HU) as well as against "QTDRED" and "DRDE" peptides from Klebsiella nitrogenase and pullulanase (NP) proteins, respectively. Multiplication of the 2 antibodies against each organism produced indices for RA-HU and AS-NP. RESULTS: Significantly increased levels of anti-HU antibodies (P<0.0001) were observed in patients with RA when compared with patients with AS or with healthy control subjects. Patients with AS were found to have significantly elevated levels of anti-NP (P<0.0001) antibodies when compared with patients with RA or with healthy subjects. Furthermore, all patients with RA were found to have values of anti-HU antibody (RA-HU) index above 95% confidence limit (CL) of the mean of healthy control subjects; meanwhile, all patients with AS were having values of anti-NP antibody (AS-NP) index above the 95% CL of the mean of healthy control subjects (100% sensitivity). However, the specificity of the RA-HU index in RA and the AS-NP index in patients with AS were 92% and 95%, respectively. CONCLUSION: The use of the RA-HU or AS-NP diagnostic index as a sole marker or in combination with other autoantibody markers could be used in the identification of patients with RA or AS, respectively. Longitudinal investigations starting with patients with early disease will be needed.

The treatment of disc herniation-induced sciatica with infliximab: results of a randomized, controlled, 3-month follow-up study.

STUDY DESIGN: A randomized controlled trial. OBJECTIVES: To evaluate the efficacy of infliximab, a monoclonal antibody against tumor necrosis factor (TNF)-alpha in a randomized controlled setting. SUMMARY OF BACKGROUND DATA: Recently, we obtained encouraging results in an open-label study of infliximab in patients with disc herniation-induced sciatica. Furthermore, the results of experimental studies support the use of infliximab in sciatica. Therefore, we initiated a randomized, controlled trial (FIRST II, Finnish Infliximab Related STudy) to confirm the efficacy of a single infusion of infliximab for sciatic pain. METHODS: Inclusion criteria were unilateral moderate to severe sciatic pain with an MRI-confirmed disc herniation concordant with the symptoms and signs of radicular pain. Patients had to be candidates for discectomy, as evaluated by an independent orthopedic surgeon. Forty patients were allocated to a single intravenous infusion of either infliximab 5 mg/kg or placebo. Assessments at baseline and various time points included clinical examination with measurement of straight leg raising restriction; questionnaires related to subjective symptoms (leg and back pain by 100-mm visual analog scale, Oswestry disability); sick leaves; number of discectomies; and adverse effects possibly related to treatment. The primary endpoint was a reduction in leg pain from baseline to 12 weeks, which was analyzed using a Mann-Whitney U test and repeated-measures analysis. RESULTS: A significant reduction in leg pain was observed in both groups, with no significant difference between treatment regimens. Similar efficacy was observed between treatment groups for secondary endpoints. Seven patients in each group required surgery. No adverse effects related to treatment were encountered. CONCLUSIONS: The results of this randomized trial do not support the use of infliximab for lumbar radicular pain in patients with disc herniation-induced sciatica.

Efficacy of infliximab for disc herniation-induced sciatica: one-year follow-up.

STUDY DESIGN: An open-label trial. OBJECTIVES: To test the long-term efficacy of infliximab, a monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha), in disc herniation-induced sciatica. SUMMARY OF BACKGROUND DATA: Our recent trial indicated that a single infusion of 3 mg/weight-kg of infliximab produced a rapid curative effect in disc herniation-induced sciatica. Here, we describe the 1-year effect of a 3 mg/kg of infliximab in these 10 patients and our experience with a lower dose of 1 mg/kg of infliximab for the same indication in 2 additional patients. METHODS: Patients with severe sciatica were treated with a single infusion of infliximab, 3 mg/weight-kg in 10 patients and 1 mg/kg in 2 patients, intravenously over 2 hours. The outcomes (leg and back pain on a 100-mm visual scale, Oswestry disability, clinical signs) were assessed at 1 week, 2 weeks, 1 month, 3 months, 6 months, and 1 year after the infusion. The outcomes with 3 mg/kg of infliximab were compared to 62 patients who received periradicular saline for sciatica in a previous trial. The resorption rate of disc herniations from baseline to 1 year was compared between infliximab and control groups. RESULTS: The response to 1 mg/kg of infliximab for leg pain was good only in 1 of the 2 patients treated, whereas the response to 3 mg/kg of infliximab for leg pain was sustained in most patients over the 1-year follow-up. The 1-year response significantly favored 3 mg/kg of infliximab over periradicular saline in leg pain (P = 0.005) and disability (P = 0.003). Neurologic abnormalities normalized more comprehensively in the infliximab group (P = 0.001). Reduction in disc herniation volume did not differ between the infliximab-treated patients and controls. CONCLUSIONS: The results showed that the beneficial effect of a single infusion of 3 mg/kg of infliximab for herniation-induced sciatica is sustained in most patients over a 1-year follow-up period. Furthermore, infliximab does not seem to interfere with the spontaneous resorption of disc herniations.

Retardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with disease-modifying antirheumatic drugs: five-year experience from the FIN-RACo study.

OBJECTIVE: To evaluate the long-term frequency of disease remissions and the progression of joint damage in patients with early rheumatoid arthritis (RA) who were initially randomized to 2 years of treatment with either a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or a single DMARD. METHODS: In this multicenter prospective followup study, a cohort of 195 patients with early, clinically active RA was randomly assigned to treatment with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone or with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the DMARD and prednisolone treatments became unrestricted, but were still targeted toward remission. The long-term effectiveness was assessed by recording the frequency of remissions and the extent of joint damage seen on radiographs of the hands and feet obtained annually up to 5 years. Radiographs were assessed by the Larsen score. RESULTS: A total of 160 patients (78 in the combination group and 82 in the single group) completed the 5-year extension study. At 2 years, 40% of the patients in the combination-DMARD group and 18% in the single-DMARD group had achieved remission (P < 0.009). At 5 years, the corresponding percentages were 28% and 22% (P not significant). The median Larsen radiologic damage scores at baseline, 2 years, and 5 years in the combination-DMARD and single-DMARD groups were 0 and 2 (P = 0.50), 4 and 12 (P = 0.005), and 11 and 24 (P = 0.001), respectively. CONCLUSION: Aggressive initial treatment of early RA with the combination of 3 DMARDs for the first 2 years limits the peripheral joint damage for at least 5 years. Our results confirm the earlier concept that triple therapy with combinations of DMARDs contributes to an improved long-term radiologic outcome in patients with early and clinically active RA.

Impact of initial aggressive drug treatment with a combination of disease-modifying antirheumatic drugs on the development of work disability in early rheumatoid arthritis: a five-year randomized followup trial.

OBJECTIVE: To compare the efficacy of therapy with a combination of disease-modifying antirheumatic drugs (DMARDs) versus therapy with a single DMARD in the prevention of work disability in patients with early rheumatoid arthritis (RA). METHODS: In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recent-onset RA were randomly assigned to receive either combination therapy with DMARDs (sulfasalazine, methotrexate, hydroxychloroquine) plus prednisolone or single therapy with a DMARD with or without prednisolone. After 2 years, the drug treatment strategy was no longer restricted. At baseline, 162 patients (80 in the combination-treatment group and 82 in the single-treatment group) were still working or at least available for work. After 5 years of followup, data on all sick leave and retirement were obtained from social insurance registers or case records. The main outcome for each patient was the cumulative duration of all sick leaves and RA-related disability pensions, divided by the observation period during which the patient was not retired because of another disease or because of age. RESULTS: The cumulative duration of work disability per patient-observation year was significantly lower in those randomized to combination therapy than in those randomized to single therapy: median 12.4 days (interquartile range [IQR] 0-54) versus 32.2 days (IQR 6-293) (P = 0.008, sex- and age-adjusted P = 0.009). This was mainly due to the difference in sick leaves (i.e., work disability periods

Tumor necrosis factor-alpha monoclonal antibody, infliximab, used to manage severe sciatica.

STUDY DESIGN: An open-label study was conducted. OBJECTIVE: To evaluate the efficacy and safety of infliximab, a monoclonal chimeric antibody, against tumor necrosis factor-alpha (TNFalpha) for the treatment of severe sciatica. SUMMARY OF BACKGROUND DATA: Evidence from animal studies indicates that TNFalpha plays a role in the pathophysiology of sciatica. Anti-TNFalpha therapy has not been previously evaluated in sciatic patients. METHODS: In this study, 10 patients with disc herniation-induced severe sciatica received infliximab (Remicade 3 mg/kg) intravenously over 2 hours. The outcome was assessed at 1 hour, 1 week, 2 weeks, 1 month, and 3 months after the infusion and compared to historical control subjects consisting of 62 patients who received saline in a trial of periradicular infiltration for sciatica. Leg pain was the primary outcome, with more than a 75% decrease from the baseline score constituting a painless state. Fisher's exact test and repeated measures analysis of variance were used for statistical analysis. RESULTS: At 1 hour after the infusion, leg pain had decreased by 50%. At 2 weeks, 60% of the patients in the infliximab group were painless, as compared with 16% of the control patients (P = 0.006). The difference was sustained at 3 months (90% vs 46%; P = 0.014). Infliximab was superior over the whole follow-up period in terms of leg pain (P = 0.003) and back-related disability (P = 0.004). At 1 month, every patient in the infliximab group had returned to work, whereas 38% of the control subjects still were on sick leave (P = 0.02). None of the patients treated with infliximab underwent surgery during the follow-up period. No immediate or delayed adverse drug reactions and no adverse effects related to medication were observed. CONCLUSIONS: Anti-TNFalpha therapy is a promising treatment option for sciatica. There is an urgent need for a randomized controlled trial to evaluate whether thesepromising early results can be confirmed.

Inadequately low serum levels of steroid hormones in relation to interleukin-6 and tumor necrosis factor in untreated patients with early rheumatoid arthritis and reactive arthritis.

OBJECTIVE: To compare levels of steroid hormones in relation to cytokines and to study levels of cortisol or dehydroepiandrosterone (DHEA) in relation to other adrenal hormones in untreated patients with early rheumatoid arthritis (RA) and reactive arthritis (ReA) compared with healthy controls. METHODS: In a retrospective study with 34 RA patients, 46 ReA patients, and 112 healthy subjects, we measured serum levels of interleukin-6 (IL-6), tumor necrosis factor (TNF), adrenocorticotropic hormone (ACTH), cortisol, 17-hydroxyprogesterone (17-OH-progesterone), androstenedione (ASD), DHEA, and DHEA sulfate (DHEAS). RESULTS: RA patients had higher serum levels of IL-6, TNF, cortisol, and DHEA compared with ReA patients and healthy subjects, but no difference was noticed with respect to ACTH and DHEAS. However, in RA and ReA patients compared with healthy subjects, levels of ACTH, cortisol, ASD, DHEAS, and 17-OH-progesterone were markedly lower in relation to levels of IL-6 and TNF. Furthermore, the number of swollen joints correlated inversely with the ratio of serum cortisol to serum IL-6 in RA (R(Rank) = -0.582, P = 0.001) and, to a lesser extent, in ReA (R(Rank) = -0.417, P = 0.011). In RA patients, the mean grip strength of both hands was positively correlated with the ratio of serum cortisol to serum IL-6 (R(Rank) = 0.472, P = 0.010). Furthermore, in these untreated patients with RA and ReA, there was a relative decrease in the secretion of 17-OH-progesterone, ASD, and DHEAS in relation to DHEA and cortisol. This indicates a relative predominance of the nonsulfated DHEA and cortisol in relation to all other measured adrenal steroid hormones in the early stages of these inflammatory diseases. CONCLUSION: This study indicates that levels of ACTH and cortisol are relatively low in relation to levels of IL-6 and TNF in untreated patients with early RA and ReA compared with healthy subjects. The study further demonstrates that there is a relative increase of DHEA and cortisol in relation to other adrenal hormones, such as DHEAS. This study emphasizes that adrenal steroid secretion is inadequately low in relation to inflammation. Although changes in hormone levels are similar in RA and ReA, alteration of steroidogenesis is more pronounced in RA patients than in ReA patients.