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

June 11, 2014

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 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 ," 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 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.

Explore further: Adalimumab is a promising therapy for children with Crohn's disease

More information: Abstract Numbers: OP0074 and OP0075

Notes:

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

Related Stories

Adalimumab is a promising therapy for children with Crohn's disease

August 6, 2012
Adalimumab (an anti-tumor necrosis factor [TNF] antibody) is effective in maintaining remission in certain pediatric patients with Crohn's disease, according to a new study in Gastroenterology, the official journal of the ...

Immunogenicity strongly impacts response to adalimumab in RA

December 13, 2012
(HealthDay)—For patients with rheumatoid arthritis (RA), long-term clinical outcomes are good with etanercept and adalimumab; but for adalimumab, treatment response is strongly dependent on the presence or absence of anti-adalimumab ...

Adalimumab relieves hidradenitis suppurativa

December 18, 2012
(HealthDay)—For patients with moderate-to-severe hidradenitis suppurativa (HS), a chronic skin disease characterized by painful abscesses, nodules, and draining fistulas in the axilla and groin, treatment with once-weekly ...

High doses of saw palmetto don't impact serum PSA

February 8, 2013
(HealthDay)—Compared with placebo, saw palmetto, even at a dose as high as 960 mg, does not affect serum prostate-specific antigen (PSA) levels in men with lower urinary tract symptoms, according to research published in ...

Brodalumab demonstrates significant clinical response in psoriatic arthritis

June 12, 2013
A new study presented today at EULAR 2013, the Annual Congress of the European League Against Rheumatism, shows that treatment with brodalumab demonstrates significant clinical response and an acceptable safety profile in ...

Long-term apremilast demonstrates continued efficacy in patients with psoriatic arthritis

June 12, 2013
New data presented today at EULAR 2013, the Annual Congress of the European League Against Rheumatism show that apremilast administered to patients with psoriatic arthritis continues to demonstrate meaningful clinical responses ...

Recommended for you

Study shows prevalence of knee osteoarthritis has doubled since World War II

August 14, 2017
The average American today is twice as likely to be diagnosed with knee osteoarthritis than in the years before World War II, Harvard scientists say, but that increase can't be blamed on the reasons most might think.

Researchers find arthritis drug could treat blood cancer patients

August 3, 2017
Blood cancer sufferers could be treated with a simple arthritis drug, scientists at the University of Sheffield have discovered.

Fluid in the knee holds clues for why osteoarthritis is more common in females

June 26, 2017
Researchers have more evidence that males and females are different, this time in the fluid that helps protect the cartilage in their knee joints.

Biologics before triple therapy not cost effective for rheumatoid arthritis

May 29, 2017
Stepping up to biologic therapy when methotrexate monotherapy fails offers minimal incremental benefit over using a combination of drugs known as triple therapy, yet incurs large costs for treating rheumatoid arthritis (RA). ...

Drug for refractory psoriatic arthritis shows promise in clinical trial

May 24, 2017
In a pivotal phase-3 clinical trial led by a Stanford University School of Medicine investigator, patients with psoriatic arthritis for whom standard-of-care pharmaceutical treatments have provided no lasting relief experienced ...

Cross-species links identified for osteoarthritis

May 17, 2017
New research from the University of Liverpool, published today in the journal npj Systems Biology and Applications, has identified 'cell messages' that could help identify the early stages of osteoarthritis (OA).

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.