Rheumatoid Arthritis: Wick MC

Weiss RJ, Ehlin A, Montgomery SM, Wick MC, Stark A, Wretenberg P. · Department of Molecular Medicine and Surgery, Section of Orthopaedics and Sports Medicine, Karolinska Institutet/Karolinska University Hospital, S-171 76 Stockholm, Sweden. · Rheumatology (Oxford). · Pubmed #18296481 No free full text.

Abstract: OBJECTIVES: To describe the overall use and temporal trends in orthopaedic upper limb surgery associated with RA on a nation wide basis in Sweden between 1998 and 2004. METHODS: Data for all inpatient visits during 1998-2004 for patients older than 18 yrs with RA-related diagnoses were extracted from the Swedish National Hospital Discharge Registry (SNHDR). The SNHDR prospectively collects data on all hospital admissions in Sweden according to the International Classification of Diseases (ICD). Data were analysed with respect to orthopaedic surgery of the hand, elbow and shoulder. RESULTS: During the study period, 54,579 individual RA patients were admitted to a Swedish hospital and 9% of these underwent RA-related surgery of the upper limbs. The RA patient cohort underwent a total of 8251 RA-related upper limb surgical procedures. The hand (77%) was most frequently operated on, followed by the shoulder (13%) and the elbow (10%). There was a statistically significant decrease of 31% for all admissions associated with RA-related upper limb surgery during 1998-2004 (P = 0.001). Some 10% of all RA-related upper limb surgery was due to total joint arthroplasties (TJAs), mostly for the elbow (59%). During 1998-2004, all TJAs, elbow-TJAs and shoulder-TJAs had a stable occurrence. In contrast, the overall numbers of hand-TJAs significantly increased (P = 0.009). CONCLUSIONS: Rates of RA-related upper limb surgery decreased and TJAs had a stable occurrence in Sweden during 1998-2004. The findings of this study may reflect trends in disease management and health outcomes of RA patients in Sweden.

Mathsson L, Mullazehi M, Wick MC, Sjöberg O, van Vollenhoven R, Klareskog L, Rönnelid J. · Uppsala University, Uppsala, Sweden. · Arthritis Rheum. · Pubmed #18163519 links to  free full text

Abstract: OBJECTIVE: The Sa autoantigen can be found in inflamed synovium of patients with rheumatoid arthritis (RA), and at least part of the humoral RA-specific anti-Sa response is directed against citrullinated vimentin. This study was undertaken to evaluate the sensitivity, specificity, and prognostic value of determination of levels of antibodies against modified citrullinated vimentin (anti-MCV) as compared with antibodies against cyclic citrullinated peptides (anti-CCP) in an inception cohort of patients with early RA. METHODS: Clinical data, radiographs, and measurements of levels of anti-MCV and anti-CCP antibodies were obtained in 273 patients with early RA at baseline, after 3 months, and after 1, 2, 3, and 5 years. Autoantibodies were also analyzed in 100 healthy controls. RESULTS: Of the 273 patients, 193 (70.7%) were anti-MCV positive and 158 (57.9%) were anti-CCP positive at the time of diagnosis, with nearly equal specificities (95% and 96%, respectively). Forty (14.7%) were anti-MCV positive only, and 5 (1.8%) were anti-CCP positive only. Anti-MCV-positive and anti-MCV-negative patients had similar disease activity at baseline, but presence of anti-MCV was predictive of subsequent high disease activity and continued radiographic progression. Changes in anti-MCV level showed stronger correlation with changes in clinical parameters than did changes in anti-CCP level. The subgroup of patients who were anti-MCV positive and anti-CCP negative showed a higher rate of radiographic destruction than did patients who were negative for both anti-MCV and anti-CCP. CONCLUSION: These findings show that when patients with early RA are compared with healthy controls, analysis of anti-MCV yields greater sensitivity and unchanged specificity as compared with analysis of anti-CCP. Anti-MCV also appears to perform better than anti-CCP in identifying poor radiographic prognosis in patients with early RA.

Weiss RJ, Broström E, Stark A, Wick MC, Wretenberg P. · Department of Molecular Medicine and Surgery, Karolinska Institutet 171 76 Stockholm, Sweden. · Rheumatology (Oxford). · Pubmed #17409135 links to  free full text

Abstract: OBJECTIVES: To evaluate the effects of ankle/hindfoot arthrodesis in rheumatoid arthritis (RA) patients on gait pattern of the knee and hip. METHODS: In this prospective follow-up study, 14 RA patients scheduled for ankle/hindfoot arthrodesis (talo-calcaneal, talo-navicular, calcaneo-cuboid and/or talo-crural joints) and 14 age- and sex-matched healthy controls were included. Three-dimensional gait analyses of joint angles, moments and work were performed at the index operation and after 13 months of follow-up. Each patient underwent clinical assessments of pain while walking, overall evaluation of disease activity, Health Related Quality of Life Questionnaire (EQ-5D), activity limitations, maximum walking distance, difficulty with walking surface and gait abnormality. For comparisons of pre- vs post-operative conditions, Wilcoxon's matched pairs test and Friedman ANOVA by rank test were used. RESULTS: At follow-up after ankle/hindfoot fusion surgery, RA patients demonstrated a statistically significant improvement in mean range of joint motions, moments and work in the overlying joints such as the knee and hip. Moreover, there was significantly less pain, disease activity, activity limitation, difficulty with walking surface and gait abnormality. EQ-5D and maximum walking distance were also significantly improved at follow-up. CONCLUSIONS: Our results demonstrate that ankle/hindfoot arthrodesis in RA is an effective intervention to reduce pain and to improve Health Related Quality of Life and functional ability. Moreover, the overlying leg joints experience an improvement in joint motion, muscle-generated joint moments and work during walking. Three-dimensional gait analysis may assist future investigations of the effects of orthopaedic surgery on functional mobility in RA to prevent irreversible disablement.

Wick MC, Ernestam S, Lindblad S, Bratt J, Klareskog L, van Vollenhoven RF. · Department of Rheumatology, Karolinska University Hospital, Solna, Sweden. · Scand J Rheumatol. · Pubmed #16234182 No free full text.

Abstract: OBJECTIVES: To determine whether the tumour necrosis factor-alpha (TNF-alpha) antagonist adalimumab (Humira) can be efficacious after secondary loss of efficacy (i.e. loss of clinical response in patients who had initially demonstrated clinical response) to infliximab (Remicade) or etanercept (Enbrel). PATIENTS AND METHODS: We studied 36 patients from the Stockholm TNF-alpha follow-up registry (STURE) who received adalimumab after secondary loss of efficacy to infliximab (group A, n = 27) or etanercept (group B, n = 9), and 26 patients who were started on adalimumab as the first TNF-alpha antagonist (group C). RESULTS: In group A, the baseline disease activity score 28 (DAS28) at infliximab institution was 5.5+/-0.2. During infliximab treatment, the mean best DAS28 was 3.7+/-0.2 (p<0.001), but increased to 5.2+/-0.3 when infliximab was stopped. After 3 months on adalimumab, the mean DAS28 decreased to 4.5+/-0.3 (p<0.003), and then to 4.2+/-0.2 at 6 months (p<0.001). In group B, the baseline DAS28 at etanercept institution was 6.6+/-0.5. During etanercept treatment, the mean best DAS28 was 4.6+/-0.5 (p<0.01), but increased to 5.7+/-0.4 by the time etanercept was stopped. After 3 months on adalimumab, the mean DAS28 decreased to 4.8+/-0.3 (p<0.005), and to 4.1+/-0.2 at 6 months (p<0.001). In group C, the mean baseline DAS28 was 5.6+/-0.3. After 6 months of adalimumab therapy, the DAS28 decreased to 3.5+/-0.4 (p<0.001). ACR20 responses with adalimumab in groups A, B, and C were similar (70-78%). CONCLUSIONS: For patients with secondary loss of efficacy from infliximab or etanercept, switching to adalimumab can restore a good clinical response.

Weiss RJ, Erlandsson Harris H, Wick MC, Wretenberg P, Stark A, Palmblad K. · Department of Orthopaedic Surgery, Karolinska University Hospital, Stockholm, Sweden. · Scand J Immunol. · Pubmed #16092922 No free full text.

Abstract: Bone loss represents a major unsolved problem in rheumatoid arthritis (RA). The receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for the development and activation of osteoclasts, which are key mediators of bone erosions. This study was performed to determine temporal and spatial expression of RANKL compared with the potentially destructive cytokine interleukin-1beta (IL-1beta), related to progression of synovitis and joint destruction in collagen-induced arthritis (CIA), a model of RA. CIA was induced in dark agouti (DA) rats, and tissue specimens were obtained for immunohistochemical analyses at various time points before and after disease onset. Arthritis was monitored visually, and joint pathology was examined histologically. No disease-preceding expression of RANKL was detected. However, a marked increase of both RANKL- and IL-1beta-expressing cells correlated with the progression of synovial inflammation and clinical disease severity. Abundant and concomitant expression of these cytokines was detected at sites of bone erosion, where a colocalization by osteoclast-like multinuclear tartrate-resistant acid phosphatase (TRAP)+ cells was noted. In contrast to the paucity of RANKL expression in cartilage, an abundant expression of IL-1beta was demonstrated, particularly in superficial cartilage layers. These data support the hypothesis that RANKL and IL-1beta are central contributors to joint destruction in CIA.

Weiss RJ, Stark A, Wick MC, Ehlin A, Palmblad K, Wretenberg P. · Department of Orthopaedic Surgery, Karolinska University Hospital, S-171 76 Stockholm, Sweden. · Ann Rheum Dis. · Pubmed #16079168 links to  free full text

Abstract: OBJECTIVES: To analyse changes in the rates of hospital admission and use of orthopaedic surgery to the lower limbs in Swedish patients with rheumatoid arthritis between 1987 and 2001. METHODS: Data for all rheumatoid patients admitted to hospital between 1987 and 2001 were abstracted from the Swedish National Hospital Discharge Register (SNHDR). The data in the register are collected prospectively, recording all inpatient admissions throughout Sweden. The SNHDR uses the codes for diagnoses at discharge and surgical procedures according to the Swedish version of the International Classification of Diseases (ICD). RESULTS: In all, 49,802 individual patients with rheumatoid arthritis were identified, accounting for 159,888 inpatient visits. Hospital admissions for rheumatoid arthritis decreased by 42% (p<0.001) during the period 1987 to 2001. Twelve per cent of all admissions were for a rheumatoid arthritis related surgical procedure to the lower limbs; those admissions decreased markedly (by 16%) between 1987 and 1996, and by 12% between 1997 and 2001, as did the overall number of rheumatoid arthritis related surgical procedures to the lower limbs during both time periods. Between 1997 and 2001, 47% of all rheumatoid arthritis related surgical procedures were total joint arthroplasties. There was an overall trend towards reduced length of hospital stay after orthopaedic surgery to the lower limbs during the study period. CONCLUSIONS: Rates of hospital admission and rheumatoid arthritis related surgical procedures to the lower limbs in Swedish patients with rheumatoid arthritis decreased between 1987 and 2001. This may reflect trends in disease severity, management, and health outcomes of this disease in Sweden.

Rönnelid J, Wick MC, Lampa J, Lindblad S, Nordmark B, Klareskog L, van Vollenhoven RF. · Unit of Clinical Immunology, Rudbeck Laboratory C5, SE-75185 Uppsala, Sweden. · Ann Rheum Dis. · Pubmed #15843452 links to  free full text

Abstract: OBJECTIVE: To study serum levels of citrullinated protein/peptide antibodies (anti-CP) during up to 5 years' follow up of patients with early rheumatoid arthritis (RA), and to relate serum levels to disease course and to treatments in clinical practice. METHODS: 279 patients with early RA were followed up with clinical investigations, radiographs, and measurement of anti-CP at baseline and after 3 months, 1, 2, 3, and 5 years. RESULTS: 160/279 (57.3%) patients were anti-CP positive at the first visit (mean 5 months after first symptoms). During follow up only 11/279 (3.9%) of the patients changed their anti-CP status. Anti-CP levels fell significantly during the first year, and this drop correlated with the extent of sulfasalazine treatment but not with other drugs or clinical indices. Anti-CP positive and negative patients had similar disease activities at baseline, but during follow up the anti-CP positive patients had worse clinical disease and greater radiological progression, despite at least equally intensive antirheumatic treatment. CONCLUSIONS: Anti-CP are stable during the first 5 years of RA, suggesting that events before rather than after onset of clinical manifestations of disease determine this phenotype. The presence of anti-CP at diagnosis predicts a less favourable disease course and greater radiological progression despite antirheumatic treatment, but subsequent changes in antibody levels do not reflect changes in disease activity. Taken together, these observations suggest that anti-CP positive RA is a distinct clinical and pathophysiological entity.

Wick MC, Lindblad S, Weiss RJ, Klareskog L, van Vollenhoven RF. · Department of Medicine at Karolinska University Hospital, Stockholm, Sweden. · Scand J Rheumatol. · Pubmed #15794195 No free full text.

Abstract: OBJECTIVES: Disease-modifying anti-rheumatic drugs (DMARDs) decrease clinical signs and symptoms in rheumatoid arthritis (RA). However, radiographic changes sometimes continue to accrue despite effective suppression of clinical symptoms by therapy. The objective of this study was to identify whether successful clinical disease-control in a Swedish early RA-inception cohort of patients led to an attenuation of radiological progression. PATIENTS AND METHODS: We analysed clinical data and radiographs of 95 patients who were on a stable treatment regimen [methotrexate (MTX), sulfasalazine (SSZ), oral gold (AUR)] or who had changed between different DMARDs during the 2-year observation period [multiple therapy failures (mTF)]. Radiographs were quantified using the modified Larsen score and 'X-Ray RheumaCoach' software. RESULTS: Clinical measures improved markedly (p <0.001) from baseline to year 2 under AUR, MTX, and SSZ therapy but not in the mTF group. Similar levels of disease control were seen for each DMARD. During this period, patients treated with AUR had a deltaLarsen score (+ 14.5+/-1.3) similar to mTF patients (+ 15.8+/-1.1) but greater than patients on MTX (+8.6+/-0.8) or SSZ (+9.1+/-0.8). CONCLUSIONS: This study confirms that radiological progression occurs despite a clinically acceptable disease control, but also shows that, given the same degree of clinical disease control, radiological progression can be different for different DMARDs.

Wick MC, Anderwald C, Weiss RJ, Imhof H, Kainberger F, Smolen JS. · Rheumatology Unit, Department of Medicine at Karolinska Hospital, Stockholm, Sweden. · Scand J Rheumatol. · Pubmed #15228186 No free full text.

Abstract: OBJECTIVE: The efficacy of DMARD therapy in rheumatoid arthritis (RA) can be judged by radiological analysis. This study aimed to determine the time-dependent progression of joint damage, acute-phase response, and rates of radiologic progression in early DMARD-treated RA patients over 10 years. PATIENTS AND METHODS: We evaluated outpatient records, and radiographs of hands and feet of 54 early RA patients on DMARDs for 10 years. Radiographs were quantified by the Larsen method using recently developed quantification software. RESULTS: Radiological damage attenuated, with disease progression from baseline to Year 10 [correlation coefficient (r)=0.95, probability (p)<0.001]. Radiographic scores progressed more rapidly during the first 5 years than thereafter. Cumulative erythrocyte sedimentation rate (ESR) was strongly correlated with radiological progression (p<0.001, r=0.88). CONCLUSION: Our findings reveal a higher amount of radiographic RA progression during the first years of DMARD treatment. Thus, our data provide strong evidence for the importance of both early DMARD therapy and continuous radiographic assessments in RA.

Wick MC, Lindblad S, Klareskog L, Van Vollenhoven RF. · Rheumatology Unit, Department of Medicine, Karolinska Hospital, S-171 76 Stockholm, Sweden. · Ann Rheum Dis. · Pubmed #15194582 links to  free full text

Abstract: BACKGROUND: The relationship between inflammation and joint destruction in rheumatoid arthritis (RA) has not been unequivocally characterised. Joint destruction may result from the cumulative inflammatory burden over time, modified by an individual constant factor. OBJECTIVE: To test the hypothesis that the relationship between radiological progression and inflammation can mathematically be expressed as: [equation: see text] where Re is a factor that varies from person to person. METHODS: Clinical data and radiographs of 76 patients with early RA receiving different disease modifying antirheumatic drugs were analysed. Radiographs were quantified using the modified Larsen score and the "X-Ray RheumaCoach" software. The cumulative inflammatory burden was estimated by the time integrated 28 joint Disease Activity Score (DAS28), calculated as the area under the curve. RESULTS: 76 patients with early RA who started treatment with methotrexate (n = 20), sulfasalazine (n = 37), or oral gold (n = 19) monotherapy were evaluated. The mean (SEM) DAS28 decreased from 4.6 (0.1) at baseline to 2.3 (0.1) after 2 years. The mean (SEM) DeltaLarsen score from baseline to year 2 was 10.3 (1.5). Correlation between cumulative inflammation and radiographic change was poor. In contrast, when calculating a person's factor Re in year 1 ( Re 1) and year 2 ( Re 2), a strong and significant correlation (r = 0.58, p<0.000001) was seen between Re 1 and Re 2. CONCLUSIONS: Joint destruction is the result of the cumulative burden of inflammation over time, modified by an individual factor Re that remains relatively constant over the first 2 years of observation. The data support a mathematical model that expresses the interrelationship between inflammation and joint destruction.

Wick MC, Lindblad S, Weiss RJ, Klareskog L, van Vollenhoven RF. · Rheumatology Unit, Department of Medicine at Karolinska Hospital, Stockholm, Sweden. · Ann Rheum Dis. · Pubmed #15096329 links to  free full text

Abstract: OBJECTIVE: To determine if intrapatient comparisons between prediagnosis and subsequent radiological progression could be used to assess effects of DMARDs in an RA inception cohort. PATIENTS AND METHODS: 149 non-randomised patients with newly diagnosed RA in four groups were analysed: patients treated with (a) methotrexate (n = 56); (b) sulfasalazine (n = 55); (c) auranofin (n = 19); and (d) controls who were poor treatment responders (n = 19). Radiographs were quantified using the Larsen erosion score. The prediagnosis radiological progression from the onset of RA symptoms to diagnosis was calculated and compared with the observed progression rate during the first year after diagnosis while receiving DMARD treatment. RESULTS: Mean (SD) disease duration from onset of symptoms until diagnosis was 6.7 (4.0) months. Mean (SD) baseline Larsen score was 13.2 (9.3), giving a mean (SD) estimated prediagnosis progression rate of 23.6 (12.4) Larsen score units/year. Control and auranofin groups showed radiological progression after diagnosis similar to the progression predicted by prediagnosis progression rates. Patients receiving methotrexate or sulfasalazine showed a marked reduction (71% and 73%, respectively; p<0.001) in radiographic progression compared with prediagnosis progression. CONCLUSIONS: Prediagnosis rates of radiological progression can be used quantitatively to obtain information on the potential efficacy of DMARDs, and indicate that methotrexate and sulfasalazine, but not auranofin, significantly retard radiographic damage in the first year after diagnosis.