Decrease of fructosamine levels during treatment with adalimumab in patients with both diabetes and rheumatoid arthritis

Tumour necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine which has been closely linked to obesity and insulin resistance. We present two cases of patients with rheumatoid arthritis (RA) and concomitant diabetes mellitus, who showed a marked decrease of fructosamine levels after initiating therapy with adalimumab, a TNFalpha-blocking agent, for active RA. This finding may implicate that TNFalpha blockade causes better glycaemic control in RA patients with concomitant diabetes, possibly by improving insulin resistance.     

Cost effectiveness of adalimumab in the treatment of patients with moderate to severe rheumatoid arthritis in Sweden

BACKGROUND: Societal decision makers increasingly emphasise their need for evidence based economic analyses to make reimbursement decisions. OBJECTIVE: To analyse the cost utility of adalimumab, on both incremental cost and incremental quality adjusted life years (QALYs), versus traditional disease modifying antirheumatic drugs and the other tumour necrosis factor (TNF) antagonists suitable for submission to the Swedish LFN (Pharmaceutical Benefit Board). METHODS: Swedish unit costs and treatment guidelines from a lifetime perspective were implemented. A mathematical model, incorporating data from seven trials, simulated the experiences of 10 000 hypothetical patients with moderate to severe rheumatoid arthritis (RA). The primary outcome measure-QALYs-was derived from utility values calculated from a relationship between the Health Assessment Questionnaire (HAQ) Disability Index (DI) and Health Utility Index-III (HUI-3) from adalimumab trial results. The model followed the progression of HAQ-DI through a number of treatments in a sequence accounting for mortality, drug and monitoring costs, and other direct costs. RESULTS: When using ACR50 as a response threshold for determining successful treatment, adalimumab plus methotrexate showed the greatest number of QALYs gained (2.3 from one study and 2.1 from the pooled results of two trials). The etanercept plus methotrexate strategy yielded QALY gains similar to the pooled adalimumab results. Except for the infliximab strategy, the costs results were between 35 000 and 42 000, a range normally considered cost effective in other European countries. CONCLUSION: Adalimumab appears to be cost effective for the treatment of moderate to severe RA. The results suggest that adalimumab is at least as cost effective as other TNF antagonists.     

Liver biopsy findings in patients with rheumatoid arthritis undergoing longterm treatment with methotrexate

Ten histological criteria were evaluated semiquantitatively in the liver biopsies of 60 patients with rheumatoid arthritis (RA) before initiation of methotrexate (MTX) and were compared with 40 biopsies taken during MTX treatment (mean cumulative dose 1.322 mg). Mesenchymal changes (Kupffer cell proliferation, portal tract infiltration) and parenchymal alterations (nuclear variability, ballooning, fatty infiltration) were very common without statistically significant difference between the 2 groups. Slight periportal and/or portal fibrosis was present in 25% of patients without statistical difference between groups. Central fibrosis occurred in 13.5-12.5%. We conclude that liver abnormalities in RA are not related to MTX treatment.     

Radiological and clinical results of longterm treatment of rheumatoid arthritis with methotrexate and azathioprine

OBJECTIVE: To study whether the reported superior effect of methotrexate (MTX) compared to azathioprine (AZA) in retarding radiologic progression after one year in rheumatoid arthritis was sustained at 2 and 4 years. METHODS: All 64 patients enrolled in the original randomized double blind study were invited for an open extension of followup to 4 years including 4-monthly clinical and laboratory assessments and radiographs of hands, wrists, and feet at 2 and 4 years. RESULTS: After 4 years, 18 patients (58%) from the MTX group and 7 patients (21%) from the AZA group continued the initial study drug. During followup more patients (n = 21) switched from AZA to MTX than vice versa (n = 5). In an intention-to-treat analysis improvement of clinical and laboratory variables at 4 years was more pronounced in the MTX group. Mean radiologic scores increased in both treatment groups during followup. According to an intention-to-treat analysis increase in erosion score at one and 2 years in the MTX group was significantly lower than in the AZA group: after one year MTX group 1.8 versus AZA group 5.3 (p = 0.002); after 2 years MTX 3.5 versus AZA 6.5 (p = 0.05). After 4 years there was a trend toward less progression in the MTX group: MTX 6.8 versus AZA 10.8 (p = 0.09). For the total score, progression in the MTX group was less after one and 2 years. After 4 years marked radiologic progression was observed more often in the AZA group. CONCLUSION: Drug continuation after 4 years of followup was better for MTX than for AZA. In an intention-to-treat analysis the beneficial effect of MTX on radiologic progression compared with AZA was sustained after 2 years of followup. Thereafter differences between treatment groups leveled off, probably mainly due to the greater number of switches from AZA to MTX than vice versa.     

Morbidity and mortality in rheumatoid patients during treatment with adalimumab and infliximab

SIR, Three anti-tumour necrosis factor (TNF) agents (infliximab,adalimumab and etanercept) have demonstrated impressive efficacyin the treatment of rheumatoid arthritis (RA). They have beenremarkably safe in the clinical trials reported to date [1].The occurrence of serious infection, some fatal, during anti-TNFtherapy in three UK centres led Moots et al. [2] to advocategreater caution in the use of these agents. Others have alsorecently emphasized the risk of serious bacterial infectionassociated with anti-TNF therapy [3, 4]. As of August 2002,574 deaths have occurred in 554     

Clinical and ultrasonographic monitoring of response to adalimumab treatment in rheumatoid arthritis

OBJECTIVE: To evaluate by clinical, laboratory, and sonographic assessment the effects of adalimumab therapy in patients with rheumatoid arthritis (RA) over 24 months of treatment. METHODS: Twenty-five patients with RA were commenced on adalimumab therapy. Before the beginning of the therapy (Time 0) and after 3 (T1), 12 (T2), and 24 (T3) months we evaluated erythrocyte sedimentation rate, C-reactive protein, physician and patient visual analog scale for disease activity, number of tender and swollen joints, Health Assessment Questionnaire, and Disease Activity Score in 28 joints. In addition, musculoskeletal ultrasound (US) was performed bilaterally in the 2nd and 5th metacarpophalangeal, 3rd interphalangeal, wrist, and knee joints and in the tendon sheaths and bursae of those areas. A semiquantitative score (0 3) was used to indicate the presence of a localized inflammatory process and/or structural damage. The summed total was used as an indicator of global change in each joint (single joint score). The sum of the single joint scores was used as an indicator of overall polyarticular involvement in each patient (total score). RESULTS: Patients who did not submit to the planned examinations strictly on time were excluded from the study. Then 25 patients were examined at T0 and T1, 20 at T2, and 9 at T3. All clinical and laboratory measures as well as the US scores were significantly reduced during the followup. CONCLUSION: A positive response to treatment with adalimumab was demonstrated by clinical, laboratory, and US evaluation by both short- and longterm followup.     

Osteonecrosis and monoarticular rheumatoid arthritis treated with intra-articular adalimumab

We report a 54-year-old patient with RA presented with osteonecrosis (ON) and monoarthritis of left knee remitting in the last 2 years. Monoarthritis was resistant to disease-modifying antirheumatic drugs (DMARDs) and intra-articular corticosteroids. Intra-articular administration of adalimumab provided a good clinical and radiographic response. Synovitis resolved and osteonecrosis disappeared almost totally.     

Osteonecrosis and monoarticular rheumatoid arthritis treated with intra-articular adalimumab

Abstract

We report a 54-year-old patient with RA presented with osteonecrosis (ON) and monoarthritis of left knee remitting in the last 2 years. Monoarthritis was resistant to disease-modifying antirheumatic drugs (DMARDs) and intra-articular corticosteroids. Intra-articular administration of adalimumab provided a good clinical and radiographic response. Synovitis resolved and osteonecrosis disappeared almost totally.     

Reduction of cardiovascular risk factors with longterm fish oil treatment in early rheumatoid arthritis

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased risk for cardiovascular (CV) events through multiple factors. Fish oil has been shown to reduce symptoms in RA and to reduce CV risk. We assessed the effect of an antiinflammatory dose of fish oil on CV risk factors within a program of combination chemotherapy for patients with early RA. METHODS: Patients who chose not to take fish oil (n = 13) were compared with patients who achieved a sustained elevation of eicosapentaenoic acid (EPA) in plasma phospholipid fatty acids (> 5% total fatty acids) while taking fish oil over a 3-year period (n = 18). We examined cellular content of arachidonic acid (AA), synthesis of thromboxane A2 and prostaglandin E2, use of nonsteroidal antiinflammatory drugs (NSAID), traditional CV lipid risk factors, and disease activity at 3 years. RESULTS: At 3 years, AA (as a proportion of AA plus long-chain n-3 fatty acids that can compete with AA for cyclooxygenase metabolism) was 30% lower in platelets and 40% lower in peripheral blood mononuclear cells in subjects taking fish oil. Serum thromboxane B2 was 35% lower and lipopolysaccharide-stimulated whole-blood prostaglandin E2 was 41% lower with fish oil ingestion compared to no fish oil. NSAID use was reduced by 75% from baseline with fish oil (p < 0.05) and by 37% without fish oil (NS). Favorable changes in fasting blood lipids were seen with, but not without fish oil. Remission at 3 years was more frequent with fish oil use (72%) compared to no fish oil (31%). CONCLUSION: Fish oil reduces cardiovascular risk in patients with RA through multiple mechanisms.     

Health-related quality of life in Moroccan patients with rheumatoid arthritis

We aimed to assess the aspects of health-related quality of life (HRQoL) in Moroccan patients with rheumatoid arthritis (RA) and to evaluate the disease-related parameters influencing it. Two hundred fifty-five patients with RA were consecutively included. We assessed sociodemographic characteristics, cigarette smoking status, disease duration, diagnosis delay, joint pain intensity (on a 0–100-mm visual analogue scale), disease activity (by the disease activity score (DAS 28) and biological tests), structural damage (by radiographs scored using the Sharp’s method as modified by Van der Heijde), functional disability (by the Health Assessment Questionnaire), extra-articular manifestations, immunological status, and treatments. The Arabic version of the Medical Outcomes Study Short Form 36 Health Survey (SF-36) was applied to assess HRQoL. All domains of SF-36 were deteriorated in a significant way comparing to the general population. The most affected subgroups of SF-36 were role limitation, role emotional, vitality, and social functioning. Women had significantly lower scores of SF-36 compared to men. Patients with decreased levels of education and low socioeconomic status had significantly lower scores of SF-36 (for all p?≤?0.01). Current and ex-smokers had lower scores in physical domains of quality of life. Patients treated with methotrexate had better scores of mental health. Furthermore, patients receiving biologic agents had better scores of physical and social domains. Decreased scores of SF-36 were significantly correlated with disease duration, joint pain intensity, clinical and biological disease activity, functional disability, and radiographic damage. The level of antibodies against citrullinated peptides had significant correlations with the impairment of physical domains of SF-36. Physical as well as mental aspects of HRQoL in our RA patients were significantly deteriorated. Recognizing complicated relationships between HRQoL and disease-related variables among our RA patients can help to develop further management strategies to improve patients’ daily living particularly with the advent of new treatments.     

Rheumatoid arthritis complicated with immunodeficiency-associated lymphoproliferative disorders during treatment with adalimumab

A 71-year-old woman was diagnosed with rheumatoid arthritis in 2002. Treatment was started with methotrexate and she was switched to adalimumab in 2006. In May 2008, she started complaining of swelling of the left axilla and the left elbow lymph nodes, and adalimumab was discontinued in December. Her lymphadenopathy did not resolve and she was admitted to hospital with fever in May 2009. Subsequent laboratory examinations showed that serum alkaline phosphatase, gamma-glutamyl transpeptidase, C-reactive protein, and soluble interleukin-2 receptor levels were 3,078 IU/l, 510 IU/l, 20 mg/dl, and 7,290 U/ml, respectively. Gallium scintigraphy showed high-intensity areas in the above-mentioned lymph nodes. She suddenly progressed to jaundice and died of pulmonary edema on the 25th day of hospitalization. Autopsy indicated large atypical cells with a distorted nucleus that had multiplied in the above-mentioned lymph nodes. On immunohistochemical staining these cells showed positive staining for CD15, CD30, PAX-5, Epstein-Barr virus (EBV) early small RNA (EBER), and LMP-1. Reactivation of EBV was diagnosed via EBV antibodies and an EBV DNA determination. We considered that she had developed EBV-associated lymphoproliferative disorders due to immunodeficiency caused by adalimumab administration. Reactivation of EBV associated with adalimumab and the relationship of this reactivation to malignant lymphoma have been rarely reported.     

Rheumatoid arthritis complicated with immunodeficiency-associated lymphoproliferative disorders during treatment with adalimumab

Abstract

A 71-year-old woman was diagnosed with rheumatoid arthritis in 2002. Treatment was started with methotrexate and she was switched to adalimumab in 2006. In May 2008, she started complaining of swelling of the left axilla and the left elbow lymph nodes, and adalimumab was discontinued in December. Her lymphadenopathy did not resolve and she was admitted to hospital with fever in May 2009. Subsequent laboratory examinations showed that serum alkaline phosphatase, gamma-glutamyl transpeptidase, C-reactive protein, and soluble interleukin-2 receptor levels were 3,078 IU/l, 510 IU/l, 20 mg/dl, and 7,290 U/ml, respectively. Gallium scintigraphy showed high-intensity areas in the above-mentioned lymph nodes. She suddenly progressed to jaundice and died of pulmonary edema on the 25th day of hospitalization. Autopsy indicated large atypical cells with a distorted nucleus that had multiplied in the above-mentioned lymph nodes. On immunohistochemical staining these cells showed positive staining for CD15, CD30, PAX-5, Epstein-Barr virus (EBV) early small RNA (EBER), and LMP-1. Reactivation of EBV was diagnosed via EBV antibodies and an EBV DNA determination. We considered that she had developed EBV-associated lymphoproliferative disorders due to immunodeficiency caused by adalimumab administration. Reactivation of EBV associated with adalimumab and the relationship of this reactivation to malignant lymphoma have been rarely reported.