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).
|Abstract:||The efficacy of initial and long-term prednisone < 5 mg/ day in treatment of rheumatoid arthritis (RA) by one academic rheumatologist over 25 years from 1980 to 2004 is summarized. Patient responses were assessed using a multidimensional health assessment questionnaire (MDHAQ), completed by all patients at all visits in the infrastructure of care. A database was maintained of all visits, which included medications and scores for physical function, pain, patient global estimate of status, and routine assessment of patient index data (RAPID3), an index of these 3 measures. Prednisone doses were higher in patients with more severe MDHAQ/RAPID3 scores, as expected, although formal criteria were not used to determine the initial dose. Similar improvements were seen in clinical status over 12 months in patients treated with < 5 vs [greater than or equal to] 5 mg/day prednisone and maintained for > 8 years. Adverse effects were primarily bruising and skin-thinning; levels of hypertension, diabetes, and cataracts were not higher than expected, including in 148 patients monitored over > 4 years, 75 over > 8 years. Prednisone at initial and long-term doses of < 5 mg/day appears acceptable and effective for many patients with RA at this time, although further clinical trials and long-term observational studies are needed to optimize treatment of patients with RA with low-dose prednisone. The data also illustrate that MDHAQ scores in usual clinical care can be used to document results of therapy over long periods with no extra work for the physician.|
|Article Type:||Clinical report|
(Dosage and administration)
Prednisone (Complications and side effects)
Rheumatoid arthritis (Patient outcomes)
Rheumatoid arthritis (Drug therapy)
|Publication:||Name: Bulletin of the NYU Hospital for Joint Diseases Publisher: J. Michael Ryan Publishing Co. Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2012 J. Michael Ryan Publishing Co. ISSN: 1936-9719|
|Issue:||Date: Jan 15, 2012 Source Volume: 70 Source Issue: S1|
|Geographic:||Geographic Scope: United States Geographic Code: 1USA United States|
Systemic glucocorticoids have long been recommended in RA primarily
as "bridging therapy" while awaiting anticipated benefits of
disease modifying anti-rheumatic drugs (DMARDs) or for acute severe
disease flares or life-threatening vasculitis, even in recent EULAR
guidelines. (1) Nonetheless, prednisone or prednisolone is prescribed
for long periods of time by many rheumatologists for RA in usual care
clinical settings. For example, in the international database of the
Quantitative Clinical Assessment of Patients with Rheumatoid Arthritis
(QUEST-RA) study, among 4,363 RA patients seen in usual care at 48
clinical sites (approximately 100 patients per site) in 15 countries,
66% of patients were taking glucocorticoids. (2)
The efficacy of low-dose prednisone has been documented in 7 double-blind clinical trials since 1995, (3-9) defined in the studies as 10 mg/day or less, although it has been suggested that "low-dose" might be defined as 5 mg/day or less. (10) A withdrawal clinical trial in RA patients documented clinical efficacy of prednisone in doses of 3 mg/day compared to placebo. (10) Disease-modifying properties of 5 to 7.5 mg/day prednisone, (3,7,8) confirmed in metaanalyses, (11,12) are of particular interest, as long-term doses of 10 mg/day are associated with bone loss (13) and higher mortality rates. (14,15) Doses of 5 mg/day or less of prednisone do not induce suppression of the hypothalamic-pituitary-adrenal axis in most patients (16-19) and are associated with few adverse events. (20)
In 1949 when glucocorticoids were introduced to clinical medicine by Hench and colleagues in a published report (21) as well as dramatic motion pictures, neither clinical trials nor dose-response studies were required for registration of a new therapy to be marketed to physicians for patient care. That may explain in part why prednisone was used in higher than optimal doses for many years. Nonetheless, clinical trials also have many limitations, including patient selection, inflexible dosage schedules, reporting of results in groups which may not apply to all individual patients, and many others. (22,23) Perhaps the most important limitation of clinical trials in chronic diseases involves a relatively short time frame to recognize differences as well as adverse events over 5 years or longer. Therefore, the experience of one rheumatologist (TP) over 25 years concerning treatments of RA patients with prednisone (usually in doses < 5 mg/ day in recent years with concomitant methotrexate) between 1980 and 2004 at weekly academic clinical setting, appears of interest to the rheumatology community regarding long-term efficacy and safety.
All visits of all patients over this period were entered into a database, which included medications and scores on a multidimensional health assessment questionnaire (MDHAQ) for functional status and pain. RAPID3, an index of three RA core data measures for physical function, pain, and patient global estimate (24) on the MDHAQ, was calculated at all patients seen after 1995, when patent global estimate was added to the MDHAQ. (25) RAPID3-EST, a surrogate for RAPID3 that includes only physical function and pain but is correlated with RAPID3 at rho > 0.9, was calculated on all patients as well, as it was the only self-report index available in patients seen prior to 1995. MDHAQ data allowed recognition of clinical improvement, as well as self-report of possible adverse effects, queried at each visit of low-dose < 5 mg initial and long-term prednisone, as summarized below.
Decline of Mean Initial Prednisone Dose from 10.3 mg/day in 1980 to 1985 to 3.6 mg/ day in 2000 to 2004
The mean initial prednisone dose in 308 patients with RA treated between 1980 and 2004 in 5-year periods was 10.3, 6.5, 5.1, 4.1, and 3.6 mg/day in 1980 to 1984, 1985 to 1989, 1990 to 1994, 1995 to 1999, and 2000 to 2004, respectively (Table 1). The proportion of patients whose initial dose was < 5 mg/day was 0, 4%, 23%, 67%, and 86%, compared to 5 mg/day of 51%, 80%, 70%, 26%, and 10%, and > 5 mg/ day of 49%, 16%, 7%, 7%, and 3%, in the 5-year periods, respectively (Table 1). The proportion of patients who took methotrexate rose from 10.2% to 25.9% to 56.7% to 71.0% to 77.7% in the 5-year periods. (26)
Higher Mean Initial Doses in Patients with Higher Scores for MDHAQ Physical Function, Pain, and RAPID3
Mean baseline MDHAQ physical function scores (recorded from 0 to 3 to 0 to 10) were 2.4 (on a scale of 0 to 10) in patients treated initially with < 5 mg/day and 3.5 in patients treated with [greater than or equal to] 5 mg/day (maximum 20 mg/day) (Table 2). Mean pain scores were 5.2 (on a scale of 0 to 10) in patients treated initially with < 5 mg/day and 6.3 in patients treated with [greater than or equal to] 5 mg/day. In patients treated initially with < 5 mg/day, mean RAPID3-EST was 12.4 (on a scale of 0 to 30) compared to 15.9 in those treated with [greater than or equal to] 5 mg/ day; in patients for whom the full RAPID3 was available, mean RAPID3 was 13.2 in patients treated initially with < 5 mg/day compared to 17.3 in those treated with [greater than or equal to] 5 mg/ day (data not shown).
These data indicate that patients with more severe clinical status were more likely to be treated with higher doses of prednisone > 5 mg/day, illustrating "confounding by indication" in non-randomized data. However, no patient was treated with more than 10 mg/day after 1990, and even 10 mg/day was used rarely. Higher doses of prednisone do not appear to add clinically important efficacy, while increasing adverse effects.
Similar Improvement in Clinical Status Over 12 Months Was Seen in Patients Treated with < 5 mg/day versus [greater than or equal to] 5 mg/day of Prednisone
Scores for function, pain, and RAPID3-EST fell by 34%, 37%, and 37% in patients treated with < 5 mg/day versus 40%, 37%, and 38% in patients treated with [greater than or equal to] 5 mg/day (Table 3). Substantially better results were seen after 1990, possibly associated with early concomitant methotrexate in most patients. Improvement was similar in most patients, with little difference according to dosage in different 5-year periods (Table 3).
Improved Long-term Outcomes in Patients Treated with Low-Dose (< 5 mg/day) Prednisone were Maintained Over Long Periods
All 290 patients treated between 1980 and 2005 with longitudinal data whose prednisone was begun between 1980 and 2005 and had available at least two visits were analyzed in quartiles according to duration of prednisone therapy of 1 year or less, 1.1 to 4 years, 4.1 to 8 years, and more than 8 years (Table 4). Clinical improvement was maintained for up to 8 years in most patients (Table 4), although some worsening was seen in patients with longest follow-up. These findings differ considerably from those in the 1980s and 1990s, when severe declines began after 2 to 3 years in most patients. (27,28)
Few Adverse Events in Patients Treated with Low-Dose (< 5 mg/day) Prednisone Over 5 to 15 Years (25% for Longer Than 8 Years)
Adverse events were ascertained through self-report in usual care on the MDHAQ, which includes queries about hypertension, diabetes, cataracts, weight gain, and other comorbidities. The primary adverse events were bruising and skin-thinning. In 109 patients treated after 1995, the proportion of patients with the prevalence of hypertension was 25%, diabetes 8%, and cataracts 9% (Table 5). There were six new cases of hypertension over 557 patient-years, five new cases of diabetes over 632 patient-years, and four new cases of cataracts over 617 patient-years (Table 5). Mean (median) weight gain was 1.45 kg (1.13 kg) over 48 weeks after initiation of prednisone. Weight gain was lowest in patients who began prednisone [less than or equal to] 3 mg/day (mean 0.44 kg) and greatest in patients who began prednisone > 5 mg/ day (mean 2.63 kg) (data not shown).
The data presented in this review indicate a decline in mean initial prednisone dose in 308 patients with RA treated between 1980 and 2004 from 10.3 mg/day in 1980 to 1984 to 3.6 mg/day in 2000 to 2004 (Table 1). The proportion of patients who were taking methotrexate was increased from 10% in 1985 to 77% in 2000, (26,29) which appears to explain in part reduction of the prednisone dose over this period. Low-dose prednisone, at doses < 5 mg/day, appears effective for many patients with RA at this time, including initial dose of 3 mg/day and indefinite continuation, with few adverse effects. (30)
Adverse effects were primarily bruising and skin-thinning. In 109 patients treated after 1995, the proportion of patients with the prevalence of hypertension was 25%, diabetes 8%, and cataracts 9% (Table 5). It is not possible to identify precise statistics concerning expected levels of comorbidities in RA in the total absence of glucocorticoids over 5 years or longer, and the incidence and prevalence of more feared complications of glucocorticoids therapy were not ascertained systematically as in a randomized trial. However, patients generally report development of hypertension, diabetes, and cataracts on the MDHAQ. Therefore, it is not likely that the incidence of these adverse events was substantially higher than what was found and reported. Development of diabetes, hypertension, and cataracts in fewer than 10% of patients is consistent with findings in a German database of self-report database of RA patients indicating few adverse events, (30) with the comment of Da Silva and colleagues, based on randomized trial data, that "adverse effects associated with [low-dose prednisone] are modest and often not statistically different from those of placebo." (20) Even if the level of adverse events were 25% to 50% higher, the prevalence of comorbidities is little or no more than would be expected, and might be acceptable to many doctors and patients to preserve physical function and offset joint damage.
The data concerning long-term efficacy and safety are derived from an MDHAQ, a patient-self-report questionnaire, which allowed long-term data to be collected at low cost, as the patient does most of the work. Self-report RAPID3 scores are as efficient as DAS28 (disease activity score with 28 joint count) (31) and CDAI (clinical disease activity index) (32) to distinguish active from control treatments in clinical trials involving methotrexate, (33) leflunomide, (33) anakinra, (34) adalimumab, (35) abatacept, (36) infliximab (37) and certolizumab. (38) RAPID3 scores are correlated significantly with DAS28 and CDAI scores in clinical trials (35,38-40) and usual clinical care, (41,42) including categories for high, moderate, low severity, and remission. Physical function scores on MDHAQ and other questionnaires are far more significant than radiographs or laboratory tests in the prognosis of severe outcomes in RA, including functional status, (27,43) work disability, (44-46) costs, (47) joint replacement surgery, (48) and premature death. (14,27,49-54)
It is not feasible to conduct a randomized study over periods of 3 to 5 years or longer. Furthermore, randomized trials are affected by many limitations that often are not articulated, including patient selection due to exclusion and inclusion criteria, relatively short-term periods of observation when long-term data are needed, fixed dosage of medications, limitations on changes in other medications, etc. (22,55-62) Long-term observations are required to assess the likelihood of long-term adverse events with any medication, including low-dose glucocorticoids, with effort to try to control possible confounding variables.
A database of consecutive patients may provide data that are not available through randomized controlled clinical trials, (63) which may be quite relevant to patient care. The most important consideration involves the need to include all consecutive patients, to avoid patient selection. Indeed, selection of patients in traditional clinical series provides an important rationale for a randomized clinical trial, to isolate the therapy variable compared to another therapy or a placebo while all other variables are hoped to be similar through randomization. All patients can be included through completion of MDHAQ at all patient visits in the infrastructure of patient care.
The data presented here indicate that long-term prednisone, at doses < 5 mg/day, is effective and well-tolerated for most patients with RA at this time, including initial dose of 3 mg/day and indefinite continuation. Logistic, medical, and ethical considerations would require that multiple therapies be provided to most RA patients to achieve best outcomes, and it may never be possible to isolate prednisone (or methotrexate or a biological agent or physical therapy or any single variable) for the treatment of RA (or any chronic disease) over 5 years or longer in a long-term clinical trial. However, this limitation should not deter efforts to analyze low-dose risks and benefits of low-dose prednisone in shorter clinical trials and to collect rigorous quantitative data in usual clinical care to analyze results of treatment over long periods.
MDHAQ/RAPID3 provides rigorous quantitative data in the infrastructure of clinical care, with minimal cost and extra effort on the part of true rheumatologist. MDHAQ/ RAPID3 prepares patients for a visit and improves doctor-patient communication while saving time for the doctor. All rheumatologists can use MDHAQ/RAPID to analyze results of treatments with low does prednisone and all other therapies to achieve optimal outcomes for patients with RA.
Dr. Pincus/Health Report Services, Inc., owns the copyright for the MDHAQ/RAPID3. No license is needed for clinicians who may freely use MDHAQ/RAPID3 to monitor patient status in usual clinical care. Royalties and license fee are received from for-profit pharmaceutical and electronic medical record companies for the use of MDHAQ/RAPID3. The other author has no financial or proprietary interest in the subject matter or materials discussed, including, but not limited to, employment, consultancies, stock ownership, honoraria, and paid expert testimony.
(1.) Gorter SL, Bijlsma JW, Cutolo M, 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 Jun;69(6):1010-4.
(2.) Sokka T, Kautiainen H, Toloza S, et al. QUEST-RA: quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries. Ann Rheum Dis. 2007 Nov;66(11):1491-6.
(3.) Kirwan JR. The effects of glucocorticoids on joint destruction in rheumatoid arthritis. N Engl J Med. 1995 Jul;333(3):142-6.
(4.) Boers M, Verhoeven AC, Markusse HM, et al. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet. 1997 Aug 2;350(9074):309-18.
(5.) Mottonen T, Hannonen P, Leirisalo-Repo M, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: A randomised trial. FIN-RACo trial group. Lancet. 1999 May 8;353(9164):1568-73.
(6.) van Everdingen AA, Jacobs JWG, van Reesema DRS, Bijlsma JWJ. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects. Ann Intern Med. 2002 Jan 1;136(1):1-12.
(7.) Svensson B, Boonen A, Albertsson K, et al. Low-dose prednisolone in addition to the intial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: a two-year randomized trial. Arthritis Rheum. 2005 Nov;52(11):3360-70.
(8.) 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 Nov;52(11):3371-80.
(9.) Buttgereit F, Mehta D, Kirwan J, et al. Low-dose prednisone chronotherapy for rheumatoid arthritis: a randomised clinical trial (CAPRA-2). Ann Rheum Dis. 2012 May 5. [Epub ahead of print]
(10.) Pincus T, Swearingen CJ, Luta G, Sokka T. Efficacy of prednisone 1-4 mg/day in patients with rheumatoid arthritis: a randomised, double-blind, placebo controlled withdrawal clinical trial. Ann Rheum Dis. 2009 Nov;68(11):1715-20.
(11.) Saag KG, Criswell LA, Sems KM, et al. Low-dose corticosteroids in rheumatoid arthritis. A meta-analysis of their moderate-term effectiveness. Arthritis Rheum. 1996; 39:1818-25.
(12.) Gotzsche PC, Johansen HK. Meta-analysis of short term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis. BMJ. 1998 Mar 14;316(7134):811-8.
(13.) Laan RF, van Riel PL, van de Putte LB, et al. Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis. A randomized, controlled study. Ann Intern Med. 1993 Nov 15;119(10):963-8.
(14.) Pincus T, Brooks RH, Callahan LF. Prediction of long-term mortality in patients with rheumatoid arthritis according to simple questionnaire and joint count measures. Ann Intern Med. 1994 Jan 1;120(1):26-34.
(15.) Wolfe F, Mitchell DM, Sibley JT, et al. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994 Apr;37(4):481-94.
(16.) Danowski TS, Bonessi JV, Sabeh G, et al. Probabilities of pituitary-adrenal responsiveness after steroid therapy. Ann Intern Med. 1964 Jul;61:11-26.
(17.) Wood JB, Frankland AW, James VH, Landon J. A rapid test of adrenocortical function. Lancet. 1965 Jan 30;1(7379):243-5.
(18.) Daly JR, Myles AB, Bacon PA, et al. Pituitary adrenal function during corticosteroid withdrawal in rheumatoid arthritis. Ann Rheum Dis. 1967 Jan;26(1):18-25.
(19.) LaRochelle GE, Jr., LaRochelle AG, Ratner RE, Borenstein DG. Recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients with rheumatic diseases receiving low-dose prednisone. Am J Med. 1993 Sep;95(3):258-64.
(20.) Da Silva JA, Jacobs JW, Kirwan JR, et al. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data. Ann Rheum Dis. 2006 Mar;65(3):285-93.
(21.) Hench PS, Kendall EC, Slocumb CH, Polley HF. The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydro-corticosterone; compound E) and of the pituitary adrenocorticotropic hormone on rheumatoid arthritis. Proc Staff Meet Mayo Clin. 1949 Apr 13;24(8):181-97.
(22.) Feinstein AR. An additional basic science for clinical medicine: II. The limitations of randomized trials. Ann Intern Med. 1983 Oct;99(4):544-50.
(23.) Pincus T, Sokka T. Clinical trials in rheumatic diseases: designs and limitations. Rheum Dis Clin N Am. 2004 Nov;30(4):701-4, v-vi.
(24.) Pincus T, Yazici Y, Bergman MJ. RAPID3, an index to assess and monitor patients with rheumatoid arthritis, without formal joint counts: similar results to DAS28 and CDAI in clinical trials and clinical care. Rheum Dis Clin North Am. 2009 Nov;35(4):773-8, viii.
(25.) Pincus T, Swearingen CJ. The HAQ compared with the MDHAQ: "keep it simple, stupid" (KISS), with feasibility and clinical value as primary criteria for patient questionnaires in usual clinical care. Rheum Dis Clin North Am. 2009 Nov;35(4):787-98, ix.
(26.) Sokka T, Pincus T. Ascendancy of weekly low-dose methotrexate in usual care of rheumatoid arthritis from 1980 to 2004 at two sites in Finland and the United States. Rheumatology (Oxford). 2008 Oct;47(10):1543-7.
(27.) Pincus T, Callahan LF, Sale WG, et al. Severe functional declines, work disability, and increased mortality in seventy-five rheumatoid arthritis patients studied over nine years. Arthritis Rheum. 1984 Aug;27(8):864-72.
(28.) Wolfe F, Hawley DJ. Remission in rheumatoid arthritis. J Rheumatol. 1985 Apr;12(2):245-52.
(29.) Pincus T, Sokka T, Kautiainen H. Patients seen for standard rheumatoid arthritis care have significantly better articular, radiographic, laboratory, and functional status in 2000 than in 1985. Arthritis Rheum. 2005 Apr;52(4):1009-19.
(30.) Huscher D, Thiele K, Gromnica-Ihle E, et al. Dose-related patterns of glucocorticoid-induced side effects. Ann Rheum Dis. 2009 Jul;68(7):1119-24.
(31.) Prevoo MLL, van't Hof MA, Kuper HH, et al. PLCM. 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 Jan;38(1):44-8.
(32.) Aletaha D, Smolen J. The simplified disease activity index (SDAI) and the clinical disease activity index (CDAI): a review of their usefulness and validity in rheumatoid arthritis. Clin Exp Rheumatol. 2005 Sep-Oct;23(5 Suppl 39):S100-8.
(33.) Strand V, Cohen S, Crawford B, et al. Patient-reported outcomes better discriminate active treatment from placebo in randomized controlled trials in rheumatoid arthritis. Rheumatology. 2004 May;43(5):640-7.
(34.) Cohen SB, Strand V, Aguilar D, Ofman JJ. Patient- versus physician-reported outcomes in rheumatoid arthritis patients treated with recombinant interleukin-1 receptor antagonist (anakinra) therapy. Rheumatology (Oxford). 2004 Jun;43(6):704-11.
(35.) Pincus T, Amara I, Segurado OG, et al. Relative efficiencies of physician/assessor global estimates and patient questionnaire measures are similar to or greater than joint counts to distinguish adalimumab from control treatments in rheumatoid arthritis clinical trials. J Rheumatol. 2008 Feb;35(2):201-5.
(36.) Wells G, Li T, Maxwell L, et al. Responsiveness of patient reported outcomes including fatigue, sleep quality, activity limitation, and quality of life following treatment with abatacept for rheumatoid arthritis. Ann Rheum Dis. 2008 Feb;67(2):260-5.
(37.) Pincus T, Zelinger D, Bolce RJ. High/moderate versus low activity/remission patient proportions are similar according to DAS28 (disease activity score), CDAI (clinical disease activity index) and RAPID3 (routine assessment of patient index data) in ATTRACT and ASPIRE Infliximab (INFX) clinical trials in patients with rheumatoid arthritis (RA). Ann Rheum Dis. 2009;68(Suppl 3):433.
(38.) Pincus T, Furer V, Keystone E, et al. RAPID3 (routine assessment of patient index data) severity categories and response criteria: Similar results to DAS28 and CDAI in the RAPID1 (rheumatoid arthritis prevention of structural damage) clinical trial of certolizumab pegol (CZP). Arthritis Care Res (Hoboken). 2011 Aug;63(8):1142-9. doi: 10.1002/acr.20481.
(39.) Pincus T, Bergman MJ, Yazici Y, et al. An index of only patient-reported outcome measures, routine assessment of patient index data 3 (RAPID3), in two abatacept clinical trials: similar results to disease activity score (DAS28) and other RAPID indices that include physician-reported measures. Rheumatology (Oxford). 2008 Mar;47(3):345-9.
(40.) Pincus T, Hines P, Bergman MJ, et al. Proposed severity and response criteria for Routine Assessment of Patient Index Data (RAPID3): results for categories of disease activity and response criteria in abatacept clinical trials. J Rheumatol. 2011 Dec;38(12):2565-71.
(41.) Pincus T, Swearingen CJ, Bergman M, Yazici Y. RAPID3 (routine assessment of patient index data 3), a rheumatoid arthritis index without formal joint counts for routine care: Proposed severity categories compared to DAS and CDAI categories. J Rheumatol. 2008 Nov; 35(11):2136-47.
(42.) Pincus T, Swearingen CJ, Bergman MJ, et al. RAPID3 on an MDHAQ is correlated significantly with activity levels of DAS28 and CDAI, but scored in 5 versus more than 90 seconds. Arthritis Care Res. 2010 Feb;62(2):181-9.
(43.) Wolfe F, Cathey MA. The assessment and prediction of functional disability in rheumatoid arthritis. J Rheumatol. 1991 Sep;18(9):1298-306.
(44.) Callahan LF, Bloch DA, Pincus T. Identification of work disability in rheumatoid arthritis: Physical, radiographic and laboratory variables do not add explanatory power to demographic and functional variables. J Clin Epidemiol. 1992 Feb;45(2):127-38.
(45.) Wolfe F, Hawley DJ. The longterm outcomes of rheumatoid arthritis: Work disability: A prospective 18 year study of 823 patients. J Rheumatol. 1998 Nov;25(11):2108-17.
(46.) Sokka T, Kautiainen H, Mottonen T, Hannonen P. Work disability in rheumatoid arthritis 10 years after the diagnosis. J Rheumatol. 1999 Aug;26(8):1681-5.
(47.) Lubeck DP, Spitz PW, Fries JF, et al. A multicenter study of annual health service utilization and costs in rheumatoid arthritis. Arthritis Rheum. 1986 Apr;29(4):488-93.
(48.) Wolfe F, Zwillich SH. The long-term outcomes of rheumatoid arthritis: A 23-year prospective, longitudinal study of total joint replacement and its predictors in 1,600 patients with rheumatoid arthritis. Arthritis Rheum. 1998 Jun;41(6):1072-82.
(49.) Wolfe F, Kleinheksel SM, Cathey MA, et al. The clinical value of the Stanford health assessment questionnaire functional disability Index in patients with rheumatoid arthritis. J Rheumatol. 1988 Oct;15(10):1480-8.
(50.) Leigh JP, Fries JF. Mortality predictors among 263 patients with rheumatoid arthritis. J Rheumatol. 1991 Sep;18(9):1307 12.
(51.) Callahan LF, Cordray DS, Wells G, Pincus T. Formal education and five-year mortality in rheumatoid arthritis: Mediation by helplessness scale scores. Arthritis Care Res. 1996 Dec;9(6):463-72.
(52.) Callahan LF, Pincus T, Huston JW, III, et al. Measures of activity and damage in rheumatoid arthritis: Depiction of changes and prediction of mortality over five years. Arthritis Care Res. 1997 Dec;10(6):381-94.
(53.) Soderlin MK, Nieminen P, Hakala M. Functional status predicts mortality in a community based rheumatoid arthritis population. J Rheumatol. 1998 Oct;25(10):1895-9.
(54.) Sokka T, Hakkinen A, Krishnan E, Hannonen P. Similar prediction of mortality by the health assessment questionnaire in patients with rheumatoid arthritis and the general population. Ann Rheum Dis. 2004 May;63(5):494-7.
(55.) Pincus T. Rheumatoid arthritis: disappointing long-term outcomes despite successful short-term clinical trials. J Clin Epidemiol. 1988;41(11):1037-41.
(56.) Pincus T. Limitations of randomized controlled clinical trials to recognize possible advantages of combination therapies in rheumatic diseases. Semin Arthritis Rheum. 1993 Oct;23(2 Suppl 1):2-10.
(57.) Fleming TR, DeMets DL. Surrogate end points in clinical trials: Are we being misled? Ann Intern Med. 1996 Oct 1;125(7):605-13.
(58.) Pincus T, Stein CM. Why randomized controlled clinical trials do not depict accurately long-term outcomes in rheumatoid arthritis: Some explanations and suggestions for future studies. Clin Exp Rheumatol. 1997 May-Jun;15 Suppl 17:S27-S38.
(59.) Pincus T. Limitations of randomized clinical trials in chronic diseases: explanations and recommendations. Adv Mind Body Med. 2002 Winter;18(2):14-21.
(60.) Fransen J, van Riel PLCM. Are better endpoints and better design of clinical trials needed? Best Pract Res Clin Rheumatol. 2004 Feb;18(1):97-109.
(61.) Pincus T, Yazici Y, Sokka T. Are excellent systematic reviews of clinical trials useful for patient care? Nat Clin Pract Rheu matol. 2008 Jun;4(6):294-5.
(62.) Pincus T, Furer V, Sokka T. Underestimation of the efficacy, effectiveness, tolerability, and safety of weekly low-dose methotrexate in information presented to physicians and patients. Clin Exp Rheumatol. 2010 Sep-Oct;28(5 Suppl 61):S68-S79.
(63.) Moses LE. The series of consecutive cases as a device for assessing outcomes of intervention. N Engl J Med. 1984 Sep 13;311(11):705-10.
Theodore Pincus, M.D., and Isabel Castrejon, M.D., are in the Department of Medicine, Division of Rheumatology, New York University School of Medicine and NYU Hospital for Joint Diseases, New York, New York.
Correspondence: Theodore Pincus, M.D., Division of Rheumatology, NYU Hospital for Joint Diseases, 301 East 17th Street, Room 1608, New York, NY 10003; email@example.com.
Table 1 Initial Prednisone Dose in 308 Patients with Rheumatoid Arthritis (RA) Seen from 1980 Through 2004 Percentage of Patients Mean (median) Taking Initial Dose Year First N initial Seen dose: mg/d < 5 mg/d = 5 mg/d > 5 mg/d 1980-1984 37 10.3 (5) 0 51% 49% 1985-1989 74 6.5 (5) 4% 80% 16% 1990-1994 77 5.1 (5) 23% 70% 7% 1995-1999 61 4.1 (3) 67% 26% 7% 2000-2004 59 3.6 (3) 86% 10% 3% Table 2 Baseline and Endpoint (12/month) Scores on Multidimensional Health Assessment Questionnaire (MDHAQ) for Physical Function (FN) and Pain in 308 Patients with Rheumatoid Arthritis, According to Initial Prednisone Dose < 5 Versus [greater than or equal to] 5 mg/day Mean Initial Dose < 5 mg/day (Median) Initial MDHAQ-FN MDHAQ-Pain Year First Dose Seen (mg/d) N Baseline 12 Mo. Baseline 12 Mo. 1980-1984 10.3 (5) 0 -- -- -- -- 1985-1989 6.5 (5) 3 1.4 1.5 5.3 5.7 1990-1994 5.1 (5) 18 1.7 1.3 4.7 2.7 1995-1999 4.1 (3) 41 2.7 1.8 4.6 3.2 2000-2004 3.6 (3) 51 2.6 1.6 5.9 3.5 TOTAL 5.6 (5) 113 2.4 1.6 5.2 3.3 Initial Dose [greater than or equal to] 5 mg/day MDHAQ-FN MDHAQ-Pain Year First Seen N Baseline 12 Mo. Baseline 12 Mo. 1980-1984 37 4.1 2.7 6.4 4.8 1985-1989 71 3.3 1.8 6.3 3.7 1990-1994 59 3.2 1.8 5.9 3.3 1995-1999 20 3.9 2.9 6.3 5.1 2000-2004 8 4.3 3.2 7.0 5.3 TOTAL 195 3.5 2.1 6.3 4.0 Table 3 Percentage Changes in Scores on Multidimensional Health Assessment Questionnaire (MDHAQ) for Physical Function (FN), Pain (PN), and RAPID3/estimate (RAPID3/EST) Over 12 Months in 308 Patients According to Initial Prednisone Dose < 5 versus [greater than or equal to] 5 mg/day Percent Clinical Mean Change Over 12 Months * (Median) Initial Initial Dose < 5 mg/day Year First Dose Seen (mg/d) N FN PN RAPID3-EST 1980-1984 10.3 (5) 0 -- -- -- 1985-1989 6.5 (5) 3 -5% -8% -24% 1990-1994 5.1 (5) 18 +26% +43% +38% 1995-1999 4.1 (3) 41 +33% +30% +37% 2000-2004 3.6 (3) 51 +37% +41% +39% TOTAL 5.6 (5) 113 +34% +37% +37% Percent Clinical Change Over 12 Months * Initial Dose [greater than or equal to] 5 mg/day Year First Seen N FN PN RAPID3-EST 1980-1984 37 +33% +25% +28% 1985-1989 71 +45% +42% +43% 1990-1994 59 +44% +44% +42% 1995-1999 20 +27% +19% +25% 2000-2004 8 +25% +25% +30% TOTAL 195 +40% +37% +38% *"+" indicates improvement and "-" worsening in function (FN), pain (PN), and RAPID3-EST scores. Table 4 Scores on Multidimensional Health Assessment Questionnaire (MDHAQ) for Physical Function (FN), Pain, and RAPID3-EST, and New Adverse Events Reported by Patients, According to Length of Prednisone Treatment in 344 Patients with Rheumatoid Arthritis Duration of Prednisione Use No 0.1-1.0 Follow-up Years (N = 44) (N = 72) Clinical MDHAQ Variable, Mean (SD) Baseline MDHAQ-FN [0-10 scale] 3.4 (2.0) 3.2 (2.0) Last visit MDHAQ-FN [0-10 scale] -- 2.7 (2.3) Baseline MDHAQ-pain [0-10 scale] 5.8 (2.8) 5.9 (2.5) Last visit MDHAQ-pain [0-10 scale] -- 4.0 (3.0) Baseline RAPID3-EST [0-30 scale] 14.8 (6.7) 15.1 (6.4) Last visit RAPID3-EST [0-30 scale] -- 10.6 (7.8) Possible Adverse Events Baseline weight (lbs), mean (SD) 177.0 (51.8) 163.3 (39.1) Last visit weight (lbs), mean (SD) -- 169.8 (36.4) Hypertension, N (%) -- 1 (1.4%) Cataracts, N (%) -- 0 Diabetes, N (%) -- 0 Duration of Prednisione Use 1.1-4.0 4.1-8.0 Years Years (N = 70) (N = 75) Clinical MDHAQ Variable, Mean (SD) Baseline MDHAQ-FN [0-10 scale] 2.8 (1.6) 3.0 (2.1) Last visit MDHAQ-FN [0-10 scale] 2.3 (1.8) 2.7 (2.3) Baseline MDHAQ-pain [0-10 scale] 5.8 (2.6) 6.1 (2.4) Last visit MDHAQ-pain [0-10 scale] 4.0 (2.7) 4.1 (3.0) Baseline RAPID3-EST [0-30 scale] 14.4 (5.9) 15.0 (6.6) Last visit RAPID3-EST [0-30 scale] 10.3 (6.7) 10.9 (7.6) Possible Adverse Events Baseline weight (lbs), mean (SD) 167.3 (40.0) 161.5 (36.7) Last visit weight (lbs), mean (SD) 165.6 (38.6) 160.0 (42.4) Hypertension, N (%) 4 (5.7%) 5 (6.7%) Cataracts, N (%) 1 (1.4%) 0 Diabetes, N (%) 0 3 (4.0%) Duration of Prednisione Use > 8 Years TOTAL (N = 73) (N = 334) Clinical MDHAQ Variable, Mean (SD) Baseline MDHAQ-FN [0-10 scale] 3.3 (1.9) 3.1 (2.0) Last visit MDHAQ-FN [0-10 scale] 3.3 (2.4) 2.8 (2.2) Baseline MDHAQ-pain [0-10 scale] 5.9 (2.6) 5.9 (2.6) Last visit MDHAQ-pain [0-10 scale] 4.5 (3.2) 4.2 (3.0) Baseline RAPID3-EST [0-30 scale] 14.9 (6.6) 14.8 (6.3) Last visit RAPID3-EST [0-30 scale] 12.3 (7.9) 11.0 (7.5) Possible Adverse Events Baseline weight (lbs), mean (SD) 163.5 (38.8) 165.7 (40.7) Last visit weight (lbs), mean (SD) 161.4 (41.2) 164.2 (39.7) Hypertension, N (%) 9 (12.3%) 19 (6.6%) Cataracts, N (%) 8 (11.0%) 9 (3.1%) Diabetes, N (%) 5 (6.9%) 8 (2.8%) SD, standard deviation. Table 5 Proportion of 109 RA Patients Who Took Long-term Low- Dose Prednisone and Developed Hypertension, Diabetes, and Cataracts Patients N (%) at N (%) N New Cases (Mean Years Comorbidity Baseline Overall Number of Years) at Risk Hypertension 21 (19%) 27 (25%) 6 (5.2 Years) 557 Diabetes 4 (4%) 9 (8%) 5 (5.0 Years) 632 Cataracts 6 (6%) 10 (9%) 4 (2.5 Years) 617
|Gale Copyright:||Copyright 2012 Gale, Cengage Learning. All rights reserved.|