Diagnostic value of a 3-day course of prednisolone in patients with possible rheumatoid arthritis - the TryCort study

Uta Kiltz, Christine von Zabern, Xenofon Baraliakos, Frank Heldmann, Bernd Mintrop, Michael Sarholz, Dietmar Krause, Friedrich Dybowski, Ludwig Kalthoff, Jürgen Braun, Uta Kiltz, Christine von Zabern, Xenofon Baraliakos, Frank Heldmann, Bernd Mintrop, Michael Sarholz, Dietmar Krause, Friedrich Dybowski, Ludwig Kalthoff, Jürgen Braun

Abstract

Background: In patients with tender and swollen finger joints, the differential diagnosis between rheumatoid arthritis (RA) and osteoarthritis (OA) of the hands can be initially difficult. This prospective study (the TryCort study) was performed to study the diagnostic value of prednisolone in differentiating between RA and hand OA. We present the results of this potentially diagnostic test in patients with possible RA in daily clinical practice by demonstrating the results of a pilot and a validation part of this 'prednisolone test' (pred-test).

Methods: We investigated the response to a 3-day course of 20 mg of prednisolone in patients with suspicion of RA. All patients received 1 g of paracetamol per day for 5 days for pain relief. On days 3-5, a morning dose of 20 mg of prednisolone was added. Hand pain was quantified on a 0-10 Numerical Rating Scale, and the subjective percentage of improvement (0-100%) was recorded. Thresholds for response to prednisolone were investigated in a pilot phase with differentiation in response between patients with RA and patients with OA of the hands, both with pain in the hands ≥4. In a validation phase, the best differentiating cut-off of the pilot phase was applied to discriminate responders from non-responders in consecutive patients with hand pain ≥4 referred because of suspected RA. Final diagnoses were made by the expert upon re-examination at week 12. Primary outcomes were the sensitivity and specificity of a positive test in relation to the diagnosis.

Results: A percentage of 40% subjective improvement of pain in the hands on day 3 discriminated best between RA and OA in the pilot phase. Among 95 patients with complete data in the validation phase, RA was diagnosed in about 50%. Patients with RA had more swollen joints, higher C-reactive protein levels and slightly higher Health Assessment Questionnaire scores. The pred-test was positive in 42.1% of all patients (40 of 95). The median percentage of improvement on day 5 was higher in RA than in non-RA: 50% (IQR 30-60%) vs. 20% (IQR 10-30%) (p < 0.001). The sensitivity and specificity of the pred-test were 0.6 (95% CI 0.5-0.8) and 0.8 (95% CI 0.7-0.9), respectively, and the positive and negative predictive values were 0.77 and 0.70, respectively.

Conclusions: To our knowledge, this is the first evaluation of the widely used pred-test that has ever been performed. The pred-test had a moderate sensitivity and a good specificity. We conclude that rheumatologists may use this test in unclear clinical situations to better differentiate between inflammatory and other conditions.

Trial registration: ClinicalTrials.gov identifier: NCT01395251 . Registered on 14 Jul 2011. EudraCT number: 2011-002633-19. Registered on 21 Dec 2011.

Figures

Fig. 1
Fig. 1
Study design of the pilot (a) and validation (b) phases
Fig. 2
Fig. 2
Flow diagram of the validation phase. RA Rheumatoid arthritis
Fig. 3
Fig. 3
Difference between RA and non-RA regarding the mean improvement of pain in the hands after prednisolone test in the pilot and validation phases. RA Rheumatoid arthritis, OA Osteoarthritis
Fig. 4
Fig. 4
ROC curve of the diagnostic utility of the prednisolone test in the validation phase

References

    1. Jakobsson U, Hallberg IR. Pain and quality of life among older people with rheumatoid arthritis and/or osteoarthritis: a literature review. J Clin Nurs. 2002;11(4):430–43. doi: 10.1046/j.1365-2702.2002.00624.x.
    1. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, 3rd, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–81. doi: 10.1002/art.27584.
    1. Altman R, Alarcón G, Appelrouth D, Bloch D, Borenstein D, Brandt K, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. Arthritis Rheum. 1990;33(11):1601–10. doi: 10.1002/art.1780331101.
    1. Radner H, Neogi T, Smolen JS, Aletaha D. Performance of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: a systematic literature review. Ann Rheum Dis. 2014;73(1):114–23. doi: 10.1136/annrheumdis-2013-203284.
    1. van Aken J, van Dongen H, Le Cessie S, Allaart CF, Breedveld FC, Huizinga TW. Comparison of long term outcome of patients with rheumatoid arthritis presenting with undifferentiated arthritis or with rheumatoid arthritis: an observational cohort study. Ann Rheum Dis. 2006;65(1):20–5. doi: 10.1136/ard.2005.038471.
    1. Wenham CYJ, Hensor EMA, Grainger AJ, Hodgson R, Balamoody S, Doré CJ, et al. A randomized, double-blind, placebo-controlled trial of low-dose oral prednisolone for treating painful hand osteoarthritis. Rheumatology (Oxford) 2012;51(12):2286–94. doi: 10.1093/rheumatology/kes219.
    1. Frisell T, Hellgren K, Alfredsson L, Raychaudhuri S, Klareskog L, Askling J. Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: a register-based case-control study in Sweden. Ann Rheum Dis. 2016;75(1):183–9. doi: 10.1136/annrheumdis-2014-206133.
    1. Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010;376(9746):1094–108. doi: 10.1016/S0140-6736(10)60826-4.
    1. Nieuwenhuis WP, Krabben A, Stomp W, Huizinga TW, van der Heijde D, Bloem JL, et al. Evaluation of magnetic resonance imaging-detected tenosynovitis in the hand and wrist in early arthritis. Arthritis Rheumatol. 2015;67(4):869–76. doi: 10.1002/art.39000.
    1. Glimm AM, Werner SG, Burmester GR, Backhaus M, Ohrndorf S. Analysis of distribution and severity of inflammation in patients with osteoarthritis compared to rheumatoid arthritis by ICG-enhanced fluorescence optical imaging and musculoskeletal ultrasound: a pilot study. Ann Rheum Dis. 2016;75(3):566–70. doi: 10.1136/annrheumdis-2015-207345.
    1. Ward LE, Polley HF, Power MH, Mason HL, Slocumb CH, Hench PS. Prednisone in rheumatoid arthritis: metabolic and clinical effects. Ann Rheum Dis. 1958;17(2):145–59. doi: 10.1136/ard.17.2.145.
    1. Gorter SL, Bijlsma JW, Cutolo M, Gomez-Reino J, Kouloumas M, Smolen JS, et al. Current evidence for the management of rheumatoid arthritis with glucocorticoids: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2010;69(6):1010–4. doi: 10.1136/ard.2009.127332.
    1. Dernis E, Ruyssen-Witrand A, Mouterde G, Maillefert JF, Tebib J, Cantagrel A, et al. Use of glucocorticoids in rheumatoid arthritis – practical modalities of glucocorticoid therapy: recommendations for clinical practice based on data from the literature and expert opinion. Joint Bone Spine. 2010;77(5):451–7. doi: 10.1016/j.jbspin.2009.12.010.
    1. Bijlsma JW. Disease control with glucocorticoid therapy in rheumatoid arthritis. Rheumatology (Oxford) 2012;51(Suppl 4):iv9–13.
    1. Baschant U, Lane NE, Tuckermann J. The multiple facets of glucocorticoid action in rheumatoid arthritis. Nat Rev Rheumatol. 2012;8(11):645–55. doi: 10.1038/nrrheum.2012.166.
    1. Strehl C, Gaber T, Löwenberg M, Hommes DW, Verhaar AP, Schellmann S, et al. Origin and functional activity of the membrane-bound glucocorticoid receptor. Arthritis Rheum. 2011;63(12):3779–88. doi: 10.1002/art.30637.
    1. Prevoo ML, van ’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38(1):44–8. doi: 10.1002/art.1780380107.
    1. Stucki G, Liang MH, Stucki S, Brühlmann P, Michel BA. A self-administered rheumatoid arthritis disease activity index (RADAI) for epidemiologic research: psychometric properties and correlation with parameters of disease activity. Arthritis Rheum. 1995;38(6):795–8. doi: 10.1002/art.1780380612.
    1. Lautenschläger J, Mau W, Kohlmann T, Raspe HH, Struve F, Brückle W, et al. Comparative evaluation of a German version of the Health Assessment Questionnaire and the Hannover Functional Capacity Questionnaire [in German] Z Rheumatol. 1997;56(3):144–55. doi: 10.1007/s003930050030.
    1. Buttgereit F, Straub RH, Wehling M, Burmester G. Glucocorticoids in the treatment of rheumatic diseases: an update on the mechanisms of action. Arthritis Rheum. 2004;50(11):3408–17. doi: 10.1002/art.20583.
    1. de Jong PHP, Quax RA, Huisman M, Gerards AH, Feelders RA, de Sonnaville PB, et al. Response to glucocorticoids at 2 weeks predicts the effectiveness of DMARD induction therapy at 3 months: post hoc analyses from the tREACH study. Ann Rheum Dis. 2013;72(10):1659–63. doi: 10.1136/annrheumdis-2012-202152.
    1. Wassenberg S, Rau R, Steinfeld P, Zeidler H. Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 2005;52(11):3371–80. doi: 10.1002/art.21421.
    1. van Everdingen AA, Jacobs JWG, Siewertsz van Reesema DR, Bijlsma JWJ. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med. 2002;136(1):1–12. doi: 10.7326/0003-4819-136-1-200201010-00006.
    1. Gaujoux-Viala C, Gossec L. When and for how long should glucocorticoids be used in rheumatoid arthritis? International guidelines and recommendations. Ann N Y Acad Sci. 2014;1318:32–40. doi: 10.1111/nyas.12452.
    1. Gaujoux-Viala C, Nam J, Ramiro S, Landewé R, Buch MH, Smolen JS, et al. Efficacy of conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids and tofacitinib: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2014;73(3):510–5. doi: 10.1136/annrheumdis-2013-204588.
    1. Broekhuizen BDL, Sachs APE, Moons KGM, Cheragwandi SAA, Damsté HEJ, Wijnands GJA, et al. Diagnostic value of oral prednisolone test for chronic obstructive pulmonary disorders. Ann Fam Med. 2011;9(2):104–9. doi: 10.1370/afm.1223.
    1. Tehlirian CV, Bathon JM, Waldburger JM, Firestein GS, Oliver AM, St Clair EW. Rheumatoid arthritis. In: Klippel JH, Stone JH, Crofford LJ, White PH, editors. Primer on the rheumatic diseases. 13. New York: Springer Science + Business Media; 2008. pp. 114–41.
    1. Wevers-de Boer K, Visser K, Heimans L, Ronday HK, Molenaar E, Groenendael JH, et al. Remission induction therapy with methotrexate and prednisone in patients with early rheumatoid and undifferentiated arthritis (the IMPROVED study) Ann Rheum Dis. 2012;71(9):1472–7. doi: 10.1136/annrheumdis-2011-200736.
    1. Stomp W, Krabben A, van der Heijde D, Huizinga TW, Bloem JL, van der Helm-van Mil AH, et al. Are rheumatoid arthritis patients discernible from other early arthritis patients using 1.5T extremity magnetic resonance imaging? A large cross-sectional study. J Rheumatol. 2014;41(8):1630–7. doi: 10.3899/jrheum.131169.
    1. Pappas DA, Kent JD, Greenberg JD, Mason MA, Kremer JM, Holt RJ. Delays in initiation of disease-modifying therapy in rheumatoid arthritis patients: data from a US-based registry. Rheumatol Ther. 2015;2(2):153–64. doi: 10.1007/s40744-015-0019-6.
    1. McInnes IB, O’Dell JR. State-of-the-art: rheumatoid arthritis. Ann Rheum Dis. 2010;69(11):1898–906. doi: 10.1136/ard.2010.134684.
    1. Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995;38(6):727–35. doi: 10.1002/art.1780380602.
    1. American College of Rheumatology Committee to Reevaluate Improvement Criteria A proposed revision to the ACR20: the hybrid measure of American College of Rheumatology response. Arthritis Rheum. 2007;57(2):193–202. doi: 10.1002/art.22552.
    1. Pincus T, Sokka T. Quantitative measures for assessing rheumatoid arthritis in clinical trials and clinical care. Best Pract Res Clin Rheumatol. 2003;17(5):753–81. doi: 10.1016/S1521-6942(03)00077-9.
    1. Chung CP, Thompson JL, Koch GG, Amara I, Strand V, Pincus T. Are American College of Rheumatology 50% response criteria superior to 20% criteria in distinguishing active aggressive treatment in rheumatoid arthritis clinical trials reported since 1997? A meta-analysis of discriminant capacities. Ann Rheum Dis. 2006;65(12):1602–7. doi: 10.1136/ard.2005.048975.
    1. Landewé RBM, Boers M, Verhoeven AC, Westhovens R, van de Laar MA, Markusse HM, et al. COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum. 2002;46(2):347–56. doi: 10.1002/art.10083.
    1. den Uyl D, ter Wee M, Boers M, Kerstens P, Voskuyl A, Nurmohamed M, et al. A non-inferiority trial of an attenuated combination strategy (‘COBRA-light’) compared to the original COBRA strategy: clinical results after 26 weeks. Ann Rheum Dis. 2014;73(6):1071–8. doi: 10.1136/annrheumdis-2012-202818.
    1. Bakker MF, Jacobs JWG, Welsing PMJ, Verstappen SM, Tekstra J, Ton E, et al. Low-dose prednisone inclusion in a methotrexate-based, tight control strategy for early rheumatoid arthritis: a randomized trial. Ann Intern Med. 2012;156(5):329–39. doi: 10.7326/0003-4819-156-5-201203060-00004.
    1. Pincus T, Castrejón I. Effective initial and long-term prednisone in doses of less than 5 mg/day to treat rheumatoid arthritis: documentation using a patient self-report Multidimensional Health Assessment Questionnaire (MDHAQ) Bull NYU Hosp Jt Dis. 2012;70(Suppl 1):14–20.
    1. Trampisch US, Krause D, Trampisch HJ, Klaassen-Mielke R, Baraliakos X, Braun J. Comparison of the efficacy and safety of two starting dosages of prednisolone in early active rheumatoid arthritis (CORRA): study protocol for a randomized controlled trial. Trials. 2014;15:344. doi: 10.1186/1745-6215-15-344.

Source: PubMed

3
Suscribir