Neue Studien

ACR Scientific-Meeting 2008

Selected highlights for the clinician

Beat A. Michel

TAKAYASU
The utility of 18F-FDG PET in Takayasu arteritis. T Kamed et al. 13 patients with Takayasu arteritis fulfilling the ACR criteria were included in the study. All patients underwent enhanced CT, MRI and 18F-FDG PET before treatment with corticosteroids. All lesions found by enhanced CT or MRI were detected by the 18F-FDG PET as well. Furthermore, 18F-FDG PET could detect lesions that were normal with enhanced CT or MRI. The uptake value in the PET correlated with changes in CRP levels. 18F-FDG PET is recommended as first line investigation for the diagnosis of Takayasu arteritis. In addition this method appears to be useful in the assessment of the disease distribution and in the evaluation of the treatment.

SLE
Protective effect of hydroxychloroquine on renal damage in patients with systemic lupus erythematosus: Data from a multiethnic cohort. GI Pons-Estel et al. Hydroxychloroquine (HCQ) has been shown to be associated with decreased frequency of flares and better overall survival rates in lupus. This study investigated the effect of HCQ on the prevention of the development of renal damage. This cohort study on over 500 SLE patients found that among HCQ takers less severe disease manifestations were present after adjusting for variables associated with HCQ intake, HCQ remained highly protective for the occurrence of renal damage (hazard ratio of HCQ=0.31). The authors suggest that HCQ should represcribed to all lupus patients early in the course of the disease if renal damage is to be prevented.

Belilumab (fully human monoclonal antibody to BLyS) improved or stabilized systemic lupus erythematosus (SLE) disease activity over 3 years of therapy. W. Chatham et al. 449 SLE subjects with active SLE were studied over 52 weeks in a double-blind trial of belilumab (1, 4, 10mg/kg, monthly) vs placebo. In a continuation trial subjects received belilumab 10mg/kg from week 76. Based on a novel disease activity index belilumab treated seropositive subjects showed significantly more improvement of disease activity than placebo patients. Belilumab treatment resulted in sustained improvement in SLE disease activity through 3 years of continuous treatment.

GOUT
Etanercept for prophylaxis and steroid sparing for gout patients with renal insufficiency. CT Parker et al. 3 patients with tophaceous gout and renal insufficiency were treated with etanercept 50mg/week besides corticosteroids (all were intolerant to colchicine). All three cases showed good results over six months with reduction or discontinuation of prednisone while renal function remained stable. In all three cases drug holidays resulted in flares of the disease. Etanercept may be worth considering for treatment of gout in renal insufficiency patients.

ANKYLOSING SPONDYLITIS
Five-year efficacy and safety including patient-reported outcomes with etanercept in ankylosing spondylitis. EM Mola et al. Extension study of a 12 week randomized double-blind placebo controlled trial of 84 patients with active ankylosing spondylitis receiving etanercept vs placebo. 63% of patients completed the 5 year extension study, showing ASAS responses as well as individual components of ASAS response criteria with sustained efficacy through the 5 year duration. No cases of opportunistic infections or tuberculosis were reported.

Adalimumab is highly effective in treating patients with ankylosing spondylitis with advanced spinal fusion. M Rudwaleit et al. 1250 patients were enrolled, 27% had advanced disease and 73% hat no advanced disease. Among those with advanced disease, including patients with structural changes of more than 80% of the vertebrae, patients had an improvement in signs and symptoms of ankylosing spondylitis similar to that of patients without advanced ankylosis.

SARCOIDOSIS
TNF inhibition as novel therapy for refractory sarcoidosis: Long term follow up. NJ Sweiss et al. Retrospective analysis of 32 patients with sarcoidosis receiving infliximab or adalimumab. The majority of patients had refractory disease to corticosteroids and/or immunosuppressants (MTX, leflunomide, azathioprine, mycophenolate). All patients showed improvement in the index organ involvement. Infliximab and adalimumab appear to be an effective alternative in the treatment of resistant sarcoidosis.

RA
Clinical and radiological outcomes in recent onset rheumatoid arthritis after 5 years of DAS-steered treatment in the BeSt-Study. NB Klarenbeek et al. Initially the more than 500 patients were randomized into 4 treatment strategies (sequential monotherapy, step-up combination therapy, initial combination with prednisone and initial combination with infliximab). Therapy adjustments were made aiming at DAS < 2.4. During 5 years of DAS-steered treatment initial functional improvement of year 1 was maintained in all groups. Joint damage progression remained adequately suppressed and functional improvement was sustained with DAS-steered treatment in recent onset RA patients, regardless of treatment strategy. Patients initially treated with combination treatment still had significantly less joint damage after 5 years. 10 to 19% of patients achieved drug-free remission.

Concomitant use of statins in tocilizumab-treated patients with rheumatoid arthritis with elevated low density lipoprotein cholesterol: Analysis of five phase 3 clinical trials. MC Genovese et al. Tocilizumab has been demonstrated to be effective in the treatment of RA. However, the lipid profile is disturbed in a considerable number of such treated patients. This investigation examined the effect of statin treatment in patients with RA receiving tocilizumab in 3 clinical trials. In patients treated with statins at baseline, LDL-C levels increased less under treatment with tocilizumab than in those patients not receiving statins. The initiation of statin treatment after receiving tocilizumab was effective in reducing LDL-C levels to below baseline values.

The efficacy and safety of abatacept in methotrexate-naïve patients with early erosive rheumatoid arthritis and poor prognostic factors. R. Westhovens et al. MTX-naïve patients with early erosive disease were studied, reported are the results of the first year. This randomized double-blind study included one group to receive abatacept and methotrexate and the other group placebo and methotrexate. MTX was increased to 20mg per week, abatacept was administered at about 10mg/kg. 90% completed a study. 41% in the abatacept group achieved DAS28 remission vs 23% in the methotrexate only group which was statistically significant. Statistical significance was also achieved for the parameters ACR50 responders and ACR70 responders. The combination of abatacept plus MTX provided significantly better efficacy and favourable safety compared to 20mg MTX alone in the initial treatment of early erosive RA-patients with poor prognostic factors.

The clinical efficacy of repeated courses of rituximab and the kinetics of B cell depletion in primary rituximab non-responders. K Owczarczyk et al. 14 patients with RA primarily non-responding to a first course of rituximab standard treatment were given a second treatment with rituximab. Non-response was defined by less than 1.2 improvement in DAS28 16 weeks after the first course of rituximab treatment. In these non-responders the median change in the DAS28 score was 1.23 at week 16 following retreatment. The cumulative therapy outcome was higher in patients positive for anti-CCP antibodies (median DAS28 improvement of 2.24 vs. 1.14, respectively). Patients with an initially higher number of plasma cells showed marked benefit from rituximab retreatment.

Tocilizumab monotherapy improves rheumatoid arthritis outcomes regardless of disease duration. M Genovese et al. Over 500 patients with RA were studied, comparing two doses of tocilizumab versus initial treatment with MTX up to 20 mg per week. Results showed that tocilizumab is superior to MTX monotherapy for the treatment of RA regardless of disease duration (< 2 years vs. > 2 years). However, DAS28 remission in patients with disease duration of < 2 years was more likely than in patients with longer disease duration.

In very early rheumatoid arthritis initial aggressive treatment with methotrexate, intraarticular corticosteroids and cyclosporine resulted in 5 years sustained efficacy. ML Hetland et al. This investigator initiated randomised controlled double-blinded study on 160 patients with RA (<6 months’ disease duration) received i.a. glucocorticoid in any swollen joint in combination with step-up treatment with methotraxte + cycylosporine (or cyclosporing placebo) during the first 76 weeks. At week 68 hydroxychloroquine 200 mg per day was added and by 2 years, cyclosporine or placebo cyclosporine had been withdrawn. During follow-up, all patients received MTX and hydroxychloroquine. Sulphasalazine was added in patients with active disease and if not effective the patient was switched to biologics. I.a. glucocorticoid injections in swollen joints continued. By year 5 about 50% of patients were in ACR remission. This study suggests that aggressive conventional treatment (especially MTX and i.a. glucocorticoids) during the initial 2 years in early RA results in sustained excellent disease control at 5 years of follow-up. Aggressive non-biological therapy appears to be efficacious in the vast majority of patients with early RA.

12-month safety and efficacy data of a new night-time release prednisone for the treatment of rheumatoid arthritis in 288 patients. F Buttgereit et al. Study on the effect of a modified release tablet of prednisone that releases prednisone 4 hours after ingestion. If taken at bedtime drug release occurs during the night resulting in peak plasma levels in the early morning hours. This study investigated the effect of the modified released tablet with regard to morning stiffness and median IL-6 levels. The results after 12 month showed a significant reduction in both parameters in the longterm while the low incidence of adverse events was comparable to low dose glucocorticoid treatment (doses during the study were between 3 and 10 mg per day). The nighttime administration of prednisone via the modified release tablet provides significantly greater efficacy for at least 12 months over conventional immediate release Prednisone with a favourable comparable safety profile.

Safety and efficacy of Abatacept over 4 years of treatment in patients with rheumatoid arthritis and an inadequate response to methotrexate in the AIM trial. JM Kremer et al. The extension of the AIM trial over 4 years showed that the safety of abatacept remained consistent with the earlier phase of the study with no unique or unexpected events observed over 4 years. 76.8% of patients who entered the extension study remained on treatment at the end of the 4-year study period. Abatacept provided durable improvements in ACR responses over 4 years of treatment.

Time to treatment response with abatacept in patients with RA and an inadequate response to anti-TNF therapy. M Schiff et al. The results from the analysis of two major trials showed clinically meaningful improvement in disease activity in patients with inadequate response to anti-TNF treatment. Significant response were observed from month 2 and at month 4 approximately 70% of abatacept treated patients reached a clinically meaningful change in disease activity. This effect continued to increase over 6 months.

Rituximab fixed retreatment versus on-demand retreatment in refractory rheumatoid arthritis: comparison of two B-cell depleting strategies. YK Ono Teng et al. In this prospective open-label non-randomised two-center study examined the effect of treatment with a standard regimen of rituximab at disease relapse with a regimen of rituximab every 24 weeks independently from disease status. Both groups received 1000mg rituximab during the follow-up. 48 patients were treated. At 48 weeks, 64% after fixed retreatment versus 53% after on-demand retreatment achieved an ACR 20, 28% versus 18% an ACR 50 and 4% versus 6% an ACR 70 response. Overall fixed and on demand retreatment with rituximab showed equal efficacy and safety. Fixed retreatment was somewhat more effective in moderate and non-responders to the first course.

Continued inhibition of structural damage in rheumatoid arthritis patients treated with rituximab at two years: REFLEX-study. S Cohen et al. Rituximab significantly inhibited structural damage progression over two years, which has been already shown in the first analysis over 56 weeks. The results now demonstrated that rituximab treatment continued to inhibit joint damage after two years of treatment in patients with inadequate response to TNF-inhibitors.

Arthritis development in prospectively followed arthralgia patients is dependent on anti-citrullinated protein anti-body status. WH Bos et al. This prospective analysis on 146 patients showed that the presence of anti-citrullinated protein anti-body predicted the development of arthritis, while this is not the case for IgM rheumatoid factor. The hazard ratio of anti-body positive patients compared to anti-body negative patients was 4.7.

OSTEOPOROSIS
Teriparatide vs alendronate for treatment of glucocorticoid-induced osteoporosis: 36-month results. KG Saag et al. This multicenter, double-blind randomized trial comparing teriparatide 20µg per day to alendronate 10mg per day found a significantly greater increase in BMD in the teriparatide group at the lumbar spine and femoral neck. Fewer patients had new radiographic vertebral fractures in the teriparatide group. The frequency of new non-vertebral fractures was not significantly different between groups. Both treatments were generally well tolerated.

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