Early response to apremilast treatment in psoriatic arthritis: a real-life ultrasonographic follow-up study

Early response to apremilast treatment in psoriatic arthritis: a real-life ultrasonographic... Rheumatology key message Apremilast induces a prompt and significant ultrasonographic-detected improvement in the joint inflammatory status in PsA patients. Sir, Apremilast, competitive inhibitor of phosphodiesterase 4 (PDE4), has been recently introduced in the treatment of adult PsA patients [1]. Its efficacy and safety has been assessed in the Psoriatic Arthritis Long-term Assessment of Clinical Efficacy program, including four phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trials [2]. According to EULAR recommendations, US with power Doppler (PD) is able to detect joint inflammation and may be used to monitor PsA activity [3]. Here, the US early response to apremilast in a PsA cohort was evaluated. We longitudinally collected data about patients (Classification Criteria for Psoriatic Arthritis) referred to the Arthritis Center of Sapienza University starting apremilast in agreement with Italian Agency of Drug indications [1]. The analysis was restricted to patients treated for peripheral arthritis with a follow-up of at least 45 days. Patients provided written informed consent and the local ethical committee of “Policlinico Umberto I” of Rome, approved the study. Clinical, laboratory and US data were collected at baseline (T0) and after 45 days (T1). Disease activity was calculated by the 28-joint DAS, Clinical Disease Activity Index, Simplified Disease Activity Index and Disease Activity in PsA. The HAQ was administered at baseline. We performed a multiplanar US grey-scale and PD examination of MCP joints 1–5, PIP joints 1–5 and the wrists using a MyLab 70 XVisionGold machine (Esaote, Firenze, Italy; linear array transducer 6–18 MHz). In accordance with OMERACT definitions, synovial effusion and hypertrophy were evaluated and scored on a semi-quantitative scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe), obtaining a total US score (0–198) [4]. Statistical analysis was performed using SPSS statistical software (SPSS, Chicago, IL, USA). Quantitative variables were given as the median and interquartile range (IQR). Wilcoxon’s test was used to compare non-parametric variables and Spearman’s tests for correlation. A P-value <0.05 was considered significant. Thirteen PsA patients [2 male, 11 female; median age 63 years (IQR 19.5); median disease duration 11 years (IQR 14)] treated with apremilast (30 mg twice a day) were assessed. The drug was administered in association with glucocorticoids in seven patients (53.8%) and other synthetic DMARDs in nine patients (69.2%). Seven patients (53.8%) were previously treated with biologic DMARDs. Six patients were treated with apremilast due to a high infective risk, three for previous recent malignancy, three for biologic DMARD intolerance and one for concomitant autoimmune disease. Three patients experienced prolonged diarrhoea, leading to a reduction of drug dosage (30 mg/day). A significant reduction in the US inflammatory score was observed after 45 days [T0: 15 (IQR 7.5), T1: 3 (IQR 6.25); P < 0.0001; Fig. 1A]. Representative pre- and post-therapy US images are shown in Fig. 1B and C. An improvement in the median US score was demonstrated also in the three patients on the lower apremilast dosage [T0: 19 (IQR 10); T1: 6.5 (IQR 3.5)]. We found a reduction in the median Clinical Disease Activity Index [T0: 23 (IQR 11.5), T1: 17 (IQR 2.6)] and Simplified Disease Activity Index (T0: 23.1 (IQR 10.7), T1: 17.6 (IQR 2.8)] values, though without reaching a significant difference (P = 0.05). Fig. 1 View largeDownload slide US assessment in PsA patients treated with apremilast (A) Box and whiskers plot (median, quartiles, range) of US inflammatory score of 13 PsA patients at baseline (T0) and after 45 days of treatment (T1). (B and C) Representative pre- and post-therapy US images illustrating the second MCP joint: (B) active synovitis, with power Doppler signal at baseline (T0) and (C) the same joint after 45 days of treatment (T1), without signs of US-detected inflammation. Fig. 1 View largeDownload slide US assessment in PsA patients treated with apremilast (A) Box and whiskers plot (median, quartiles, range) of US inflammatory score of 13 PsA patients at baseline (T0) and after 45 days of treatment (T1). (B and C) Representative pre- and post-therapy US images illustrating the second MCP joint: (B) active synovitis, with power Doppler signal at baseline (T0) and (C) the same joint after 45 days of treatment (T1), without signs of US-detected inflammation. Clinimetric indexes and US score modifications were not influenced by disease duration or previous biologic or concomitant synthetic DMARDs treatment. The low patient number could have influenced this subanalysis. Thus in this real-life study, we observed an early improvement of inflammatory joint status in apremilast-treated patients, with a significant reduction in the US score after 45 days. Very few data are available concerning the use of apremilast in routine clinical practice. Abignano et al. [5] published a retrospective report about 71 PsA patients: after 6 months, 60.8% of patients were classified as responders according to the treating clinician. The response was significantly associated with disease duration and low exposure to biologic DMARDs. Only one case report has been published concerning imaging assessment of apremilast efficacy: the authors described the improvement of magnetic resonance findings in a patient treated for spine involvement [6]. In our cohort, the prompt US-detected response to apremilast did not correspond to clinimetric indices improvement. This result could be related to the higher US sensitivity compared with physical evaluation, as demonstrated by the evidence of US-detected subclinical synovitis and US synovitis in >30% of PsA patients in clinical remission [7, 8]. It should be noted that the high degree of disability [median HAQ 2.12 (IQR 0.45)] of our cohort could influence the clinimetric evaluation in terms of patient assessment. The US score improvement was observed also in patients treated with a half dose, suggesting the possibility of using apremilast at a reduced dose in specific situations and still being able to have good control of joint inflammation. The main limitation of our report is the small number of patients. Nonetheless, we provide the first evidence of the ability of apremilast to induce prompt and significant improvement in PsA joint inflammatory status. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: The authors have declared no conflicts of interest. References 1 Taylor W , Gladman D , Helliwell P et al. Classification criteria for psoriatic arthritis: development of new criteria from a large international study . Arthritis Rheum 2006 ; 54 : 2665 – 73 . Google Scholar CrossRef Search ADS PubMed 2 Reed M , Crosbie D. Apremilast in the treatment of psoriatic arthritis: a perspective review . Ther Adv Musculoskelet Dis 2017 ; 9 : 45 – 53 . Google Scholar CrossRef Search ADS PubMed 3 Mandl P , Navarro-Compan V , Terslev L et al. EULAR recommendations for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice . Ann Rheum Dis 2015 ; 74 : 1327 – 39 . Google Scholar CrossRef Search ADS PubMed 4 Wakefield RJ , Balint PV , Szkudlarek M et al. Musculoskeletal ultrasound including definitions for ultrasonographic pathology . J Rheumatol 2005 ; 32 : 2485 – 7 . Google Scholar PubMed 5 Abignano G , Fadl N , Merashli M et al. Apremilast for the treatment of active psoriatic arthritis: a single-centre real-life experience . Rheumatology 2018 ; 57 : 578 – 580 . Google Scholar CrossRef Search ADS PubMed 6 Persons B , Chawla R , Carter J. Improvement in the axial symptoms and magnetic resonance imaging findings with apremilast in psoriatic arthritis . J Clin Rheumatol 2017 ; 23 : 344 – 5 . Google Scholar CrossRef Search ADS PubMed 7 Husic R , Gretler J , Felber A et al. Disparity between ultrasound and clinical findings in psoriatic arthritis . Ann Rheum Dis 2014 ; 73 : 1529 – 36 . Google Scholar CrossRef Search ADS PubMed 8 Ruta S , Marin J , Acosta Felquer ML et al. Utility of power Doppler ultrasound-detected synovitis for the prediction of short-term flare in psoriatic patients with arthritis in clinical remission . J Rheumatol 2017 ; 44 : 1018 – 23 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Rheumatology Oxford University Press

Early response to apremilast treatment in psoriatic arthritis: a real-life ultrasonographic follow-up study

Rheumatology , Volume Advance Article (8) – May 29, 2018

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com
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1462-0324
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1462-0332
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10.1093/rheumatology/key145
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Abstract

Rheumatology key message Apremilast induces a prompt and significant ultrasonographic-detected improvement in the joint inflammatory status in PsA patients. Sir, Apremilast, competitive inhibitor of phosphodiesterase 4 (PDE4), has been recently introduced in the treatment of adult PsA patients [1]. Its efficacy and safety has been assessed in the Psoriatic Arthritis Long-term Assessment of Clinical Efficacy program, including four phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trials [2]. According to EULAR recommendations, US with power Doppler (PD) is able to detect joint inflammation and may be used to monitor PsA activity [3]. Here, the US early response to apremilast in a PsA cohort was evaluated. We longitudinally collected data about patients (Classification Criteria for Psoriatic Arthritis) referred to the Arthritis Center of Sapienza University starting apremilast in agreement with Italian Agency of Drug indications [1]. The analysis was restricted to patients treated for peripheral arthritis with a follow-up of at least 45 days. Patients provided written informed consent and the local ethical committee of “Policlinico Umberto I” of Rome, approved the study. Clinical, laboratory and US data were collected at baseline (T0) and after 45 days (T1). Disease activity was calculated by the 28-joint DAS, Clinical Disease Activity Index, Simplified Disease Activity Index and Disease Activity in PsA. The HAQ was administered at baseline. We performed a multiplanar US grey-scale and PD examination of MCP joints 1–5, PIP joints 1–5 and the wrists using a MyLab 70 XVisionGold machine (Esaote, Firenze, Italy; linear array transducer 6–18 MHz). In accordance with OMERACT definitions, synovial effusion and hypertrophy were evaluated and scored on a semi-quantitative scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe), obtaining a total US score (0–198) [4]. Statistical analysis was performed using SPSS statistical software (SPSS, Chicago, IL, USA). Quantitative variables were given as the median and interquartile range (IQR). Wilcoxon’s test was used to compare non-parametric variables and Spearman’s tests for correlation. A P-value <0.05 was considered significant. Thirteen PsA patients [2 male, 11 female; median age 63 years (IQR 19.5); median disease duration 11 years (IQR 14)] treated with apremilast (30 mg twice a day) were assessed. The drug was administered in association with glucocorticoids in seven patients (53.8%) and other synthetic DMARDs in nine patients (69.2%). Seven patients (53.8%) were previously treated with biologic DMARDs. Six patients were treated with apremilast due to a high infective risk, three for previous recent malignancy, three for biologic DMARD intolerance and one for concomitant autoimmune disease. Three patients experienced prolonged diarrhoea, leading to a reduction of drug dosage (30 mg/day). A significant reduction in the US inflammatory score was observed after 45 days [T0: 15 (IQR 7.5), T1: 3 (IQR 6.25); P < 0.0001; Fig. 1A]. Representative pre- and post-therapy US images are shown in Fig. 1B and C. An improvement in the median US score was demonstrated also in the three patients on the lower apremilast dosage [T0: 19 (IQR 10); T1: 6.5 (IQR 3.5)]. We found a reduction in the median Clinical Disease Activity Index [T0: 23 (IQR 11.5), T1: 17 (IQR 2.6)] and Simplified Disease Activity Index (T0: 23.1 (IQR 10.7), T1: 17.6 (IQR 2.8)] values, though without reaching a significant difference (P = 0.05). Fig. 1 View largeDownload slide US assessment in PsA patients treated with apremilast (A) Box and whiskers plot (median, quartiles, range) of US inflammatory score of 13 PsA patients at baseline (T0) and after 45 days of treatment (T1). (B and C) Representative pre- and post-therapy US images illustrating the second MCP joint: (B) active synovitis, with power Doppler signal at baseline (T0) and (C) the same joint after 45 days of treatment (T1), without signs of US-detected inflammation. Fig. 1 View largeDownload slide US assessment in PsA patients treated with apremilast (A) Box and whiskers plot (median, quartiles, range) of US inflammatory score of 13 PsA patients at baseline (T0) and after 45 days of treatment (T1). (B and C) Representative pre- and post-therapy US images illustrating the second MCP joint: (B) active synovitis, with power Doppler signal at baseline (T0) and (C) the same joint after 45 days of treatment (T1), without signs of US-detected inflammation. Clinimetric indexes and US score modifications were not influenced by disease duration or previous biologic or concomitant synthetic DMARDs treatment. The low patient number could have influenced this subanalysis. Thus in this real-life study, we observed an early improvement of inflammatory joint status in apremilast-treated patients, with a significant reduction in the US score after 45 days. Very few data are available concerning the use of apremilast in routine clinical practice. Abignano et al. [5] published a retrospective report about 71 PsA patients: after 6 months, 60.8% of patients were classified as responders according to the treating clinician. The response was significantly associated with disease duration and low exposure to biologic DMARDs. Only one case report has been published concerning imaging assessment of apremilast efficacy: the authors described the improvement of magnetic resonance findings in a patient treated for spine involvement [6]. In our cohort, the prompt US-detected response to apremilast did not correspond to clinimetric indices improvement. This result could be related to the higher US sensitivity compared with physical evaluation, as demonstrated by the evidence of US-detected subclinical synovitis and US synovitis in >30% of PsA patients in clinical remission [7, 8]. It should be noted that the high degree of disability [median HAQ 2.12 (IQR 0.45)] of our cohort could influence the clinimetric evaluation in terms of patient assessment. The US score improvement was observed also in patients treated with a half dose, suggesting the possibility of using apremilast at a reduced dose in specific situations and still being able to have good control of joint inflammation. The main limitation of our report is the small number of patients. Nonetheless, we provide the first evidence of the ability of apremilast to induce prompt and significant improvement in PsA joint inflammatory status. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: The authors have declared no conflicts of interest. References 1 Taylor W , Gladman D , Helliwell P et al. Classification criteria for psoriatic arthritis: development of new criteria from a large international study . Arthritis Rheum 2006 ; 54 : 2665 – 73 . Google Scholar CrossRef Search ADS PubMed 2 Reed M , Crosbie D. Apremilast in the treatment of psoriatic arthritis: a perspective review . Ther Adv Musculoskelet Dis 2017 ; 9 : 45 – 53 . Google Scholar CrossRef Search ADS PubMed 3 Mandl P , Navarro-Compan V , Terslev L et al. EULAR recommendations for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice . Ann Rheum Dis 2015 ; 74 : 1327 – 39 . Google Scholar CrossRef Search ADS PubMed 4 Wakefield RJ , Balint PV , Szkudlarek M et al. Musculoskeletal ultrasound including definitions for ultrasonographic pathology . J Rheumatol 2005 ; 32 : 2485 – 7 . Google Scholar PubMed 5 Abignano G , Fadl N , Merashli M et al. Apremilast for the treatment of active psoriatic arthritis: a single-centre real-life experience . Rheumatology 2018 ; 57 : 578 – 580 . Google Scholar CrossRef Search ADS PubMed 6 Persons B , Chawla R , Carter J. Improvement in the axial symptoms and magnetic resonance imaging findings with apremilast in psoriatic arthritis . J Clin Rheumatol 2017 ; 23 : 344 – 5 . Google Scholar CrossRef Search ADS PubMed 7 Husic R , Gretler J , Felber A et al. Disparity between ultrasound and clinical findings in psoriatic arthritis . Ann Rheum Dis 2014 ; 73 : 1529 – 36 . Google Scholar CrossRef Search ADS PubMed 8 Ruta S , Marin J , Acosta Felquer ML et al. Utility of power Doppler ultrasound-detected synovitis for the prediction of short-term flare in psoriatic patients with arthritis in clinical remission . J Rheumatol 2017 ; 44 : 1018 – 23 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

RheumatologyOxford University Press

Published: May 29, 2018

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