Early Disease Activity or Clinical Response as Predictors of Long-Term Outcomes With Certolizumab Pegol in Axial Spondyloarthritis or Psoriatic Arthritis

D van der Heijde, A Deodhar, R Fleischmann, P J Mease, M Rudwaleit, T Nurminen, O Davies, D van der Heijde, A Deodhar, R Fleischmann, P J Mease, M Rudwaleit, T Nurminen, O Davies

Abstract

Objective: Early identification of patients unlikely to achieve good long-term disease control with anti-tumor necrosis factor therapy in axial spondyloarthritis (SpA) and psoriatic arthritis (PsA) is important for physicians following treat-to-target recommendations. Here we assess associations between disease activity or clinical response during the first 12 weeks of treatment and attainment of treatment targets at week 48 in axial SpA and PsA patients receiving certolizumab pegol.

Methods: The relationship between disease activity or clinical response during the first 12 weeks of treatment and achievement of week-48 targets (for axial SpA: inactive disease based on Ankylosing Spondylitis Disease Activity Score [ASDAS] using the C-reactive protein [CRP] level, or Bath Ankylosing Spondylitis Disease Activity Index <2 with normal CRP level; and for PsA: minimal disease activity) was assessed post hoc using RAPID-axSpA and RAPID-PsA trial data.

Results: A clear relationship between disease activity from week 2 to 12 and achievement of week-48 treatment targets was observed in both axial SpA and PsA populations. In axial SpA, week-48 ASDAS inactive disease was achieved by 0% of patients (0 of 21) with ASDAS very high disease activity at week 12, compared to 68% of patients (34 of 50) with week-12 ASDAS inactive disease. For PsA, week-48 minimal disease activity was achieved by 0% of patients (0 of 26) with Disease Activity Score in 28 joints (DAS28) using the CRP level >5.1 at week 12, compared to 73% of patients (57 of 78) with DAS28-CRP <2.6. Similar results were observed regardless of the disease activity measure used. Clinical response at week 12 also predicted week-48 outcomes, though to a lesser extent than disease activity.

Conclusion: Using disease activity and the clinical response state during the first 12 weeks of certolizumab pegol treatment, it was possible to identify a subset of axial SpA and PsA patients unlikely to achieve long-term treatment goals.

Trial registration: ClinicalTrials.gov NCT01087762 NCT01087788.

© 2016, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Figures

Figure 1
Figure 1
Proportion of patients achieving disease activity targets at week 48 based on classification of disease activity at baseline, week 2, week 8, and week 12. Values are the number/total number (percentage). * = the number of axial spondyloarthritis (SpA) patients at each visit: 218 at baseline, 217 at week 2, 215 at week 8, and 211 at week 12. † = the number of psoriatic arthritis (PsA) patients at each visit: 272 at baseline, 270 at week 2, 262 at week 8, and 256 at week 12. ASDAS = Ankylosing Spondylitis Disease Activity Score; ID = inactive disease; MD = moderate disease; HD = high disease; vHD = very high disease; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; CRP = C‐reactive protein; ULN = upper limit of normal; MDA = minimal disease activity; DAS28 = Disease Activity Score in 28 joints.
Figure 2
Figure 2
Disease activity at week 12 successfully predicts lack of attainment of treatment targets. axSpA = axial spondyloarthritis; AS = ankylosing spondylitis; nr = nonradiographic; PsA = psoriatic arthritis; minDA = minimal disease activity. See Figure 1 for other definitions.
Figure 3
Figure 3
Likelihood of achieving disease activity targets at week 48 based on clinical response or on achievement of patient‐reported outcome responses at early time points. Values are the number/total number (percentage). * = the number of axial spondyloarthritis (SpA) patients at each visit: 218 at baseline, 217 at week 2, 215 at week 8, and 211 at week 12. † = the number of PsA patients at each visit: 272 at baseline, 270 at week 2, 262 at week 8, and 256 at week 12. MI = major improvement; CII = clinically important improvement; MCID = minimal clinically important difference; PsARC = Psoriatic Arthritis Response Criteria. See Figure 1 for other definitions.
Figure 4
Figure 4
Clinical response at week 12 predicts lack of attainment of treatment targets moderately well. axSpA = axial spondyloarthritis; AS = ankylosing spondylitis; nr = nonradiographic; MI = major improvement; CII = clinically important improvement; PsA = psoriatic arthritis; minDA = minimal disease activity; PsARC = Psoriatic Arthritis Response Criteria. See Figure 1 for other definitions.
Figure 5
Figure 5
Heat map representing Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity at each visit grouped by patients' week‐12 ASDAS category and sorted by baseline ASDAS.

References

    1. Smolen JS, Braun J, Dougados M, Emery P, Fitzgerald O, Helliwell P, et al. Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force. Ann Rheum Dis 2014;73:6–16.
    1. Sieper J, van der Heijde D. Nonradiographic axial spondyloarthritis: new definition of an old disease? Arthritis Rheum 2013;65:543–51.
    1. Landewé R, Braun J, Deodhar A, Dougados M, Maksymowych WP, Mease PJ, et al. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24‐week results of a double‐blind randomised placebo‐controlled phase 3 study. Ann Rheum Dis 2014;73:39–47.
    1. Mease PJ, Fleischmann R, Deodhar AA, Wollenhaupt J, Khraishi M, Kielar D, et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24‐week results of a phase 3 double‐blind randomised placebo‐controlled study (RAPID‐PsA). Ann Rheum Dis 2014;73:48–55.
    1. Rudwaleit M, Landewe R, van der Heijde D, Listing J, Brandt J, Braun J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal. Ann Rheum Dis 2009;68:770–6.
    1. Rudwaleit M, van der Heijde D, Landewe R, Listing J, Akkoc N, Brandt J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009;68:777–83.
    1. Sieper J, Landewé R, Rudwaleit M, van der Heijde D, Dougados M, Mease PJ, et al. Effect of certolizumab pegol over ninety‐six weeks in patients with axial spondyloarthritis: results from a phase III randomized trial. Arthritis Rheumatol 2015;67:668–77.
    1. Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 2006;54:2665–73.
    1. Van der Heijde D, Fleischmann R, Wollenhaupt J, Deodhar A, Kielar D, Woltering F, et al. Effect of different imputation approaches on the evaluation of radiographic progression in patients with psoriatic arthritis: results of the RAPID‐PsA 24‐week phase III double‐blind randomised placebo‐controlled study of certolizumab pegol. Ann Rheum Dis 2014;73:233–7.
    1. Mease P, Deodhar A, Fleischmann R, Wollenhaupt J, Gladman D, Leszczyński P, et al. Effect of certolizumab pegol over 96 weeks in patients with psoriatic arthritis with and without prior antitumour necrosis factor exposure. RMD Open 2015;1:e000119.
    1. Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis 2010;69:48–53.
    1. Healy PJ, Helliwell PS. Measuring clinical enthesitis in psoriatic arthritis: assessment of existing measures and development of an instrument specific to psoriatic arthritis. Arthritis Rheum 2008;59:686–91.
    1. Machado P, Landewé R, Lie E, Kvien TK, Braun J, Baker D, et al. Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut‐off values for disease activity states and improvement scores. Ann Rheum Dis 2011;70:47–53.
    1. Ramiro S, van der Heijde D, van Tubergen A, Stolwijk C, Dougados M, van den Bosch F, et al. Higher disease activity leads to more structural damage in the spine in ankylosing spondylitis: 12‐year longitudinal data from the OASIS cohort. Ann Rheum Dis 2014;73:1455–61.
    1. Poddubnyy D, Haibel H, Braun J, Rudwaleit M, Sieper J. Reaching a status of low disease activity spontaneously over two year follow‐up in active patients with non‐radiographic axial spondyloarthritis in comparison to ankylosing spondylitis not treated with TNF blockers. Ann Rheum Dis 2014;73 Suppl 2:422–3.
    1. Van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum 1998;41:1845–50.
    1. Fleischmann R, van der Heijde D, Koenig AS, Pedersen R, Szumski A, Marshall L, et al. How much does Disease Activity Score in 28 joints ESR and CRP calculations underestimate disease activity compared with the Simplified Disease Activity Index? Ann Rheum Dis 2015;74:1132–7.
    1. Felson DT, Anderson JJ, Boers M, Bombardier C, Chernoff M, Fried B, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. Arthritis Rheum 1993;36:729–40.
    1. Mease PJ. Measures of psoriatic arthritis: Tender and Swollen Joint Assessment, Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), Modified Nail Psoriasis Severity Index (mNAPSI), Mander/Newcastle Enthesitis Index (MEI), Leeds Enthesitis Index (LEI), Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht Ankylosing Spondylitis Enthesis Score (MASES), Leeds Dactylitis Index (LDI), Patient Global for Psoriatic Arthritis, Dermatology Life Quality Index (DLQI), Psoriatic Arthritis Quality of Life (PsAQOL), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT‐F), Psoriatic Arthritis Response Criteria (PsARC), Psoriatic Arthritis Joint Activity Index (PsAJAI), Disease Activity in Psoriatic Arthritis (DAPSA), and Composite Psoriatic Disease Activity Index (CPDAI). Arthritis Care Res (Hoboken) 2011;63 Suppl 11:S64–85.
    1. Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain 2008;9:105–21.
    1. Saber TP, Ng CT, Renard G, Lynch BM, Pontifex E, Walsh CA, et al. Remission in psoriatic arthritis: is it possible and how can it be predicted? Arthritis Res Ther 2010;12:R94.
    1. Glintborg B, Ostergaard M, Krogh NS, Dreyer L, Kristensen HL, Hetland ML. Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti‐tumour necrosis factor: results from 8 years' surveillance in the Danish nationwide DANBIO registry. Ann Rheum Dis 2010;69:2002–8.
    1. Lord PA, Farragher TM, Lunt M, Watson KD, Symmons DP, Hyrich KL, et al. Predictors of response to anti‐TNF therapy in ankylosing spondylitis: results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford) 2010;49:563–70.
    1. Rudwaleit M, Claudepierre P, Wordsworth P, Cortina EL, Sieper J, Kron M, et al. Effectiveness, safety, and predictors of good clinical response in 1250 patients treated with adalimumab for active ankylosing spondylitis. J Rheumatol 2009;36:801–8.
    1. Vastesaeger N, Van Der Heijde D, Inman RD, Wang Y, Deodhar A, Hsu B, et al. Predicting the outcome of ankylosing spondylitis therapy. Ann Rheum Dis 2011;70:973–81.
    1. Sieper J, van der Heijde D, Dougados M, Brown LS, Lavie F, Pangan AL. Early response to adalimumab predicts long‐term remission through 5 years of treatment in patients with ankylosing spondylitis. Ann Rheum Dis 2012;71:700–6.
    1. Zhu B, Edson‐Heredia E, Cameron GS, Shen W, Erickson J, Shrom D, et al. Early clinical response as a predictor of subsequent response to ixekizumab treatment: results from a phase II study of patients with moderate‐to‐severe plaque psoriasis. Br J Dermatol 2013;169:1337–41.
    1. Baraliakos X, Listing J, Fritz C, Haibel H, Alten R, Burmester GR, et al. Persistent clinical efficacy and safety of infliximab in ankylosing spondylitis after 8 years: early clinical response predicts long‐term outcome. Rheumatology (Oxford) 2011;50:1690–9.
    1. Takeuchi T, Yamamoto K, Yamanaka H, Ishiguro N, Tanaka Y, Eguchi K, et al. Early response to certolizumab pegol predicts long‐term outcomes in patients with active rheumatoid arthritis: results from the Japanese studies. Mod Rheumatol 2015;25:11–20.
    1. Takeuchi T, Miyasaka N, Inui T, Yano T, Yoshinari T, Abe T, et al. Prediction of clinical response after 1 year of infliximab therapy in rheumatoid arthritis based on disease activity at 3 months: posthoc analysis of the RISING study. J Rheumatol 2015;42:599–607.
    1. Curtis JR, Luijtens K, Kavanaugh A. Predicting future response to certolizumab pegol in rheumatoid arthritis patients: features at 12 weeks associated with low disease activity at 1 year. Arthritis Care Res (Hoboken) 2012;64:658–67.
    1. Van der Heijde D, Keystone EC, Curtis JR, Landewe RB, Schiff MH, Khanna D, et al. Timing and magnitude of initial change in disease activity score 28 predicts the likelihood of achieving low disease activity at 1 year in rheumatoid arthritis patients treated with certolizumab pegol: a post‐hoc analysis of the RAPID 1 trial. J Rheumatol 2012;39:1326–33.

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