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11-Jun-2014

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Contact: EULAR Press Office
eularpressoffice@cohnwolfe.com
44-078-801-73209
European League Against Rheumatism

One-third of psoriatic arthritis patients are not receiving optimal dosing of adalimumab

Low dosing of infliximab does not appear to alter treatment response or adherence

Data presented today at the European League Against Rheumatism Annual Congress (EULAR 2014) showed that a significant number of patients with psoriatic arthritis (PsA) were not receiving doses of the tumour necrosis factor-alpha (TNFα) inhibitor adalimumab necessary to achieve optimal clinical benefit.1 Further data revealed that, in the case of the TNFα inhibitor infliximab, nearly three-quarters of PsA patients were on doses lower than recommended in international guidelines. 2

In the first study, after 28 weeks of treatment one-third of PsA patients were found to have serum adalimumab trough concentrations below the 5 mg/L level shown to have an optimal effect. However, these low doses still showed reasonable efficacy1

In the second study, low dosing of infliximab in more than 70% of a population of Icelandic and Danish PsA patients did not seem to alter either treatment response or adherence to therapy2

PsA is a chronic inflammatory arthritis associated with psoriasis, which significantly impacts health-related quality of life, and may lead to severe, disabling joint damage.3 Psoriasis occurs in 1-3% of the population,4 with PsA occurring in up to 30% of those of cases.5

One third of PsA patients not receiving optimal dosing of adalimumab

Presenting the results of the Dutch study, lead author Mr. Erik Vogelzang of the Jan van Breemen Research Institute, Reade, Amsterdam, Netherlands reported that serum trough levels of adalimumab of 5- 8 mg/L appeared necessary to achieve the most optimal clinical benefit. Concentrations above 8 mg/L appeared to confer no additional benefit; however, concentrations of approximately 1.0 mg/L showed reasonable efficacy.1

"These results linking serum adalimumab trough concentrations to clinical response in PsA patients confirmed the findings from a previous study in RA patients," 6 said Mr. Erik Vogelzang.

"However, interestingly, of the 103 consecutive patients with PsA prescribed adalimumab, 36 (35%) appeared to be receiving less than optimal dosing, with a trough adalimumab concentration below 5 mg/L (the lowest point of this ideal dose range). A substantial group of PsA patients that use adalimumab are therefore not able to profit from its optimal clinical benefit," Vogelzang concluded.

This was a prospective cohort study in which 103 consecutive patients diagnosed with PsA were treated with 40 mg adalimumab subcutaneously every other week. Adalimumab concentrations at 28 weeks of treatment were measured in serum trough samples, using an enzyme linked immunosorbent assay (ELISA). Clinical response was defined as a change in disease activity score in 28 joints (ΔDAS28) between baseline and week 28. At 28 weeks of treatment, serum trough concentrations ranged from 0.0 to 18.8 mg/L, with a mean of 7.2 mg/L. In 48 (47%), trough adalimumab concentrations exceeded the optimal threshold of 8 mg/L.

Low dosing of infliximab does not appear to alter treatment response or adherence

International guidelines recommend that patients with arthritis PsA prescribed the TNFα inhibitor infliximab should be dosed with 5 mg/kg bodyweight every 8th week. However, responses to lower doses have not been previously well documented.2

Dr Bente Glintborg of the Copenhagen Centre for Arthritis Research, and Centre for Rheumatology and Spine Diseases, Glostrup Hospital, Denmark presented the clinical outcomes in a large cohort of TNFα inhibitor-naïve PsA patients treated with infliximab, stratified by country (Denmark vs. Iceland), and by their dose regimen and escalation.

"More than 70% of Icelandic and Danish PsA patients treated with infliximab received sustained doses below the recommended 5 mg/kg every eight weeks," said Dr Glintborg. "Lower start doses did not appear to affect either drug adherence or response," she added. Thus, in clinical practise a low start infliximab dose with subsequent step up therapy seems to be an efficient strategy.

Danish patients received higher infliximab doses than Icelandic patients at baseline (median (IQR) 3.1 (3.0-3.8) mg/kg vs. 2.3 (2.1-2.9) mg/kg, p<0.05) and after 12 months (3.3 (3.0-4.5) mg/kg vs. 2.9 (2.2-3.5) mg/kg, p<0.0001). In Danish patients, the start dose was ≤3 mg/kg in 110 patients (29%), 3-5 mg/kg in 157(42%), ≥5 mg/kg in 38(10%) and unregistered in 71(19%). In Icelandic patients, the corresponding numbers were 64 (74%), 17 (27%), 0 (0%) and 5 (6%). Patients with higher body weight received lower infliximab doses per kg.

"Despite these important differences between Icelandic and Danish patients, they were found to have similar one-year response rates," said Dr Glintborg. After 12 months, 58% of Danish and 66% of Icelandic patients maintained treatment. In univariate analyses stratified by country, the time until dose escalation, ACR20/50/70 or EULAR-response rates, drug adherence and one-year's disease activity were independent of the baseline dose of infliximab," Dr Glintborg explained.

This was an observational cohort study based on the nationwide DANBIO and ICEBIO registries. Among the 1,589 psoriatic arthritis patients identified in the two registries, 462 patients (29%, 376 Danish, 86 Icelandic) received treatment with infliximab. Dose escalation was defined as an increase in either the dose and/or frequency. Treatment response was evaluated by ACR20/50/70 and EULAR-good-response after six months of treatment and disease activity after one year of treatment. Kaplan-Meier plots and regression analyses were performed to analyse adherence to treatment and to identify predictors of treatment response and adherence.

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Abstract Numbers: OP0074 and OP0075

NOTES TO EDITORS: For further information on this study, or to request an interview with the study lead, please contact us via: EULAR congress Press Office: Room 104, Palais des congrès de Paris Email: eularpressoffice@cohnwolfe.com Onsite tel: +44 (0) 7880 173209 Twitter: @EULAR_Press

About EULAR

The European League Against Rheumatism (EULAR) is an umbrella organisation which represents scientific societies, health professional associations and organisations for people with rheumatic diseases throughout Europe.

EULAR aims to promote, stimulate and support the research, prevention, and treatment of rheumatic diseases and the rehabilitation of those it affects.

With 45 scientific member societies, 35 People with Arthritis and Rheumatism in Europe (PARE) organisations, 17 health professionals associations and 26 corporate members, EULAR highlights the importance of combating rheumatic diseases through both medical means and patient care.

EULAR 2014 is set to be the biggest rheumatology event in Europe with almost 14,000 scientists, physicians, allied health professionals and related audiences in attendance from 130 countries. Over the course of the congress there will be 302 oral and 1,806 poster abstract presentations, 155 sessions, 725 lectures, 33 poster tours with 421 invited speakers.

To find out more about the activities of EULAR, visit: http://www.eular.org

1 Vogelzang E et al. A concentration-effect curve of adalimumab in patients with psoriatic arthritis. EULAR 2014; Paris: Abstract OP0074
2 Glintborg B et al. Impact of different infliximab dose regimens on treatment response and drug survival in 462 patients with PsA. Results from the nationwide registries DANBIO and ICEBIO. EULAR; Paris: Abstract OP0075
3 Gladman DD. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005; 64:ii14-ii17
4 Ayala F. Clinical presentation of psoriasis. Reumatismo 2007; 59(Suppl 1):40-5
5 Zachariae H . Prevalence of joint disease in patients with psoriasis: implications for therapy. Am J Clin Dermatol 2003;4:441-7
6 Pouw MF, Krieckaert CL, Nurmo



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