[Merkel cell carcinoma during treatment with TNF-alpha inhibitors: coincidence or warning?]. / Merkelcel-carcinoom bij gebruik van TNF-α-blokkers. Toeval of waarschuwing?

BACKGROUND: Increasing numbers of patients are being treated with TNF-alpha inhibitors. Two patients in our outpatient clinic developed Merkel cell carcinoma during treatment with TNF alpha inhibitors. Since this is a very rare malignancy, this is a remarkable observation. CASE DESCRIPTION: A 70-year-old male with rheumatoid arthritis had been treated with etanercept for two years when he discovered a nodule on his elbow that started growing rapidly. It was diagnosed as Merkel cell carcinoma. Despite treatment, the patient died 2 years later. CONCLUSION: Merkel cell carcinoma is an aggressive malignancy with a clinically benign aspect. Patients treated with TNF-alpha inhibitors possibly have an increased risk of developing this malignancy.

Joint surgery in the Utrecht Rheumatoid Arthritis Cohort: the effect of treatment strategy.

OBJECTIVE: To investigate the prevalence and prognostic factors of joint surgery in a large cohort of patients with rheumatoid arthritis, whose treatment, clinical and radiographic data have been assessed at predefined points in time since disease onset. METHODS: Data on surgical interventions were retrospectively obtained from 482 patients with rheumatoid arthritis whose follow-up data for at least 2 years were available, including treatment and response to treatment during the first 2 years. Survival time until the first surgical intervention and until the first major surgical intervention was determined for the total study population by Kaplan-Meier survival curves. Three separate Cox regression analyses were carried out to determine which variables measured at baseline, during the first year and during the first 2 years were predictors for joint surgery. RESULTS: 27% of the patients underwent surgical interventions. Mean survival time until the first surgical intervention was 10.4 years. The percentage of patients with a surgical intervention was 10% lower in the group with response to treatment when compared with the non-response group. Next to a delayed start with disease-modifying antirheumatic drugs, fast radiographic progression during the first year and first 2 years was a predictor of joint surgery in the multivariate regression analyses. CONCLUSION: Treatment with disease-modifying antirheumatic drugs immediately after diagnosis results in less joint surgery when compared with a delayed start. Furthermore, joint surgery is carried out more often in patients who do not respond to treatment.

The course of radiologic damage during the first six years of rheumatoid arthritis.

OBJECTIVE: To describe the radiologic course in a large cohort of patients with early rheumatoid arthritis (RA) and to analyze individual components of damage. METHODS: Five hundred two patients with recent-onset RA (disease duration <1 year) underwent annual radiologic assessment for a maximum of 6 years in this longitudinal prospective study. The study was designed to investigate the efficacy of 3 different therapeutic strategies. For the assessment of radiologic damage, radiographs of the hands and feet were scored according to the modified Sharp/van der Heijde method (SHS; range 0-448). A mean of 2.9 (range 1-7) radiographs was read per patient. RESULTS: Stable rates of progression of the SHS, erosion score, and narrowing score were found over the course of RA: the mean rates were 8.6, 5.4, and 3.2 modified Sharp units per year, respectively. The rate of progression of newly (not previously) damaged joints declined, and the rate of progression of already damaged joints (which became more damaged) increased during followup, leading to an equal contribution to progression of the SHS at 5 years. The joints of the feet, especially the fifth metatarsophalangeal joint, generally became eroded earlier and more of them became eroded compared with the joints of the hands. CONCLUSION: Radiologic damage progresses at a constant rate. In advanced disease, monitoring the progression of previously existing damage is as important as assessing new abnormalities in previously undamaged joints. Radiographs of the feet should be included in assessments of radiologic damage that are used in clinical intervention trials and daily practice.

Can methotrexate be used as a steroid sparing agent in the treatment of polymyalgia rheumatica and giant cell arteritis?

OBJECTIVE: To investigate whether methotrexate (MTX) has a steroid sparing effect in the treatment of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). METHODS: We carried out a randomised double blind, placebo controlled study in 40 patients with PMR, six of whom also had clinical symptoms of GCA. A temporal artery biopsy specimen was available from 37 patients; GCA was found in six of the specimens. Among the six patients with clinical signs of GCA, three had a positive biopsy specimen. All patients were started on prednisone 20 mg/day, irrespective of clinical signs and biopsy result, supplemented with a weekly, blinded capsule containing either MTX 7.5 mg or placebo. The prednisone dose was decreased as soon as clinical symptoms disappeared and erythrocyte sedimentation rate, C reactive protein level, or both, had normalised. RESULTS: Twenty one patients were followed for two years, or at least one year after discontinuing medication. No differences were found between the MTX group and the placebo group concerning time to achieve remission, duration of remission, number of relapses, or cumulative prednisone doses. After 21 weeks the mean daily prednisone dose was reduced by 50%. Forty percent of all patients were able to discontinue prednisone within two years. Median duration of steroid treatment was 47.5 weeks (range 3-104). No serious complications from GCA were encountered. CONCLUSIONS: With a (rapid) steroid tapering regimen, it was possible to reduce the mean daily prednisone dose by 50% in 21 weeks and to cease prednisone in 40% of the patients within two years. With this regimen, no steroid sparing effect of MTX in a dosage of 7.5 mg/week was found.