Rheumatoid Arthritis: Segurado OG

Kivitz A, Segurado OG. · Altoona Center for Clinical Research, 1125 Old Route 220 North, Duncansville, PA 16635, USA. · Expert Rev Med Devices. · Pubmed #17359217 No free full text.

Abstract: The HUMIRA (adalimumab) Pen is a novel, integrated, disposable autoinjection delivery system for the subcutaneous injection of adalimumab. Adalimumab is a biological disease modifier for the treatment of rheumatoid arthritis and other chronic debilitating diseases mediated by tumor necrosis factor. Sustaining long-term efficacy with a biological therapy is influenced by patient adherence to the therapeutic regimen, which is often affected by the route of drug administration. Self-administered injectables offer several advantages over intravenous injections (i.e., portability, convenience and flexible scheduling). In particular, patients with chronic, debilitating diseases may need a self-administered medication available in an easy-to-use and convenient delivery device that minimizes pain and facilitates adherence to therapy. The adalimumab Pen offers these benefits and recent evidence indicates that patients overwhelmingly prefer the adalimumab Pen to the prefilled syringe.

Kivitz A, Cohen S, Dowd JE, Edwards W, Thakker S, Wellborne FR, Renz CL, Segurado OG. · Altoona Center for Clinical Research, Duncansville, Pennsylvania 16635, USA. · Clin Ther. · Pubmed #17157117 No free full text.

Abstract: BACKGROUND: Adalimumab is a therapeutic monoclonal antibody for SC administration by 2 single-use injection devices providing bioequivalent amounts of adalimumab: a ready-to-use, prefilled syringe and an integrated, disposable delivery system, the autoinjection Pen. Although pens have been shown to be preferred over syringes by patients requiring long-term SC administration of medications, there are no data on preference and pain in the use of biologics in patients with chronic inflammatory diseases. OBJECTIVE: The aim of this study was to assess injection-site pain, tolerability, and patient preference of 2 delivery systems of adalimumab. METHODS: Patients with rheumatoid arthritis were enrolled in a Phase II, multicenter, open-label, single-arm, sequential trial. Patients self-administered a standard dose of adalimumab 40 mg SC every other week at each of 3 monitored clinical visits: visit 1 (syringe), visits 2 and 3 (Pen). At each visit, patients rated their pain on an 11-point scale (0 = none to 10 = pain as bad as it could be) immediately after injection and 15-30 minutes after injection and provided their impressions of and preferences for each delivery system. Safety events were recorded throughout the study and 70 days after final study dose. RESULTS: Fifty-two patients were enrolled in the trial and completed all 3 visits (32 women, 20 men; mean [SD] age, 53.8 [12.1] years). Forty (76.9%) patients reported that the Pen was less painful than the syringe, 4 (7.7%) patients found the syringe to be less painful, and 8 (15.4%) patients had no preference. Patients had statistically significant reductions in injection-pain scores from visit 1 to visit 2 and from visit 1 to visit 3. No new safety signals or apparent differences regarding tolerability between the syringe and Pen were observed. In addition, 46 (88.5%) patients preferred the Pen, 3 (5.8%) preferred the syringe, and 3 (5.8%) had no preference. Overall, patients evaluated the Pen as easier to use (94.2%), more convenient (92.3%), requiring less time to inject (82.7%), and safer (88.5%). CONCLUSIONS: Patients experienced less pain self-administering adalimumab via the Pen and preferred it versus the syringe. Further, patients perceived the Pen to be easier to use and more convenient. Both delivery systems were generally well tolerated.

Davies A, Cifaldi MA, Segurado OG, Weisman MH. · United BioSource Corporation, London, UK. · J Rheumatol. · Pubmed #19012363 No free full text.

Abstract: OBJECTIVE: To estimate the comparative lifetime cost-effectiveness of sequenced therapy with tumor necrosis factor (TNF) antagonists as the initial therapeutic intervention for patients with early rheumatoid arthritis (RA). METHODS: Because patients with RA switch regimens many times throughout the course of disease, sequenced therapeutic interventions were modeled, continuing until the last effective agent failed or death occurred. The model used published clinical outcomes from short-term, randomized controlled trials. Direct treatment costs and costs of lost productivity were modeled for each of 5 alternative treatment sequences. Incremental cost-effectiveness ratios are expressed as quality-adjusted lifeyears (QALY) gained. RESULTS: Treatment sequences that included TNF antagonists produced a greater number of QALY than conventional disease modifying antirheumatic drug regimens alone. The cost-effectiveness of sequenced therapy initiated with adalimumab plus methotrexate (MTX) extendedly dominated both infliximab-plus-MTX-initiated and etanercept sequences. The cost of adalimumab plus MTX per QALY was US $47,157 excluding productivity losses, and $19,663 including productivity losses. A supplementary sequence that incorporated adalimumab-plus-MTX-initiated first-line therapy followed by another TNF antagonist as second-line therapy was modeled; this sequence resulted in additional QALY gained and extendedly dominated all single-TNF strategies. CONCLUSION: Of the 3 single-TNF antagonist sequences, the adalimumab-plus-MTX-initiated sequence was cost-effective in producing the greatest number of QALY. Multiple TNF strategies, such as the supplementary sequence modeled in this analysis, may be cost-effective in producing even greater health gain.

Pincus T, Amara I, Segurado OG, Bergman M, Koch GG. · New York University Hospital for Joint Diseases, New York, New York 10003, USA. · J Rheumatol. · Pubmed #18050378 No free full text.

Abstract: OBJECTIVE: To estimate relative efficiencies of the 7 rheumatoid arthritis (RA) Core Data Set measures to distinguish adalimumab from control treatments in 4 clinical trials. METHODS: Four adalimumab clinical trials were analyzed for arithmetic and percentage changes for each Core Data Set measure from baseline to endpoint: 3 assessor/physician measures -- swollen joints, tender joints, and global estimate; 1 laboratory test -- C-reactive protein; and 3 patient measures -- physical function, pain, and global estimate. Relative efficiencies of each measure to distinguish adalimumab from control group responses were assessed, with tender joint count as the referent measure. RESULTS: Relative efficiencies were in a similar range for physician/assessor, patient, and laboratory measures, with some variation between trials. Among physician/assessor measures, relative efficiencies for global estimates were greater than for swollen and tender joint counts in 8/8 comparisons. Among patient measures, relative efficiencies for global estimates were greater than for physical function and pain scores in at least 6/8 comparisons. Among all measures, relative efficiencies for patient global estimates were greater than for swollen joint counts in 5/8 comparisons, and for tender joint counts in 8/8 comparisons. CONCLUSION: Patient and physician/assessor measures distinguished adalimumab from control treatment groups in similar ranges. Among all measures, physician/assessor global estimate was most efficient, and tender joint count least efficient, in all 4 trials. This information suggests that while joint counts are the most specific measure to assess RA, their sensitivity to detect treatment effects in patients with RA is generally no greater, and usually less, than other measures.

Pincus T, Chung C, Segurado OG, Amara I, Koch GG. · Vanderbilt University Medical Center, 203 Oxford House, Nashville, TN 37232, USA. · J Rheumatol. · Pubmed #17080518 No free full text.

Abstract: OBJECTIVE: To analyze 2 indices composed of the 3 patient reported outcomes (PRO) in the American College of Rheumatology (ACR) Core Data Set--physical function, pain, and global estimate--without joint count or laboratory data, for capacities to distinguish active from control treatments in 4 pivotal clinical trials. METHODS: Data from 4 clinical trials involving adalimumab, in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARD) or as monotherapy, versus control treatment were made available to analyze properties of various indices. A categorical PRO-Index M was defined as "majority" improvement in 2 of the 3 PRO measures at 20%, 50%, and 70% levels; results were evaluated to analyze agreement with ACR20, ACR50, ACR70 responses and an "all Core Data Set measures" index based on 4 of the 7 measures having such levels of improvement. A continuous PRO-Index C was defined as the median or 2nd highest of 3 percentage differences from baseline to endpoint; results were evaluated to analyze agreement with a continuous ACR-N, "all Core Data Set measures" index, and Disease Activity Score 28 (DAS28). RESULTS: All indices distinguished active versus control treatment at similar levels, including PRO-Index M versus ACR20, ACR50, and ACR70 responses, and PRO-Index C versus DAS28. CONCLUSION: PRO indices based only on patient questionnaire data, without joint counts or laboratory tests, may be useful quantitative measures of therapeutic efficacy for use in standard rheumatology clinical care.

Weinblatt ME, Keystone EC, Furst DE, Kavanaugh AF, Chartash EK, Segurado OG. · Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 75 Francis St., Boston, MA, USA. · Ann Rheum Dis. · Pubmed #16308341 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy and safety of adalimumab plus methotrexate (MTX) given for up to 4 years in patients with active, longstanding rheumatoid arthritis. METHODS: Patients responding inadequately to MTX were entered into a 24 week, controlled study (ARMADA) with adalimumab plus MTX or placebo plus MTX, and some were enrolled in a subsequent open label extension. The efficacy and safety of treatment were evaluated. Additional analyses were made for those patients whose corticosteroid and/or MTX dosages were adjusted during the extension. RESULTS: Of 271 patients in the original ARMADA trial, 262 received at least one dose of adalimumab and were evaluated. At the time of analysis, 162/262 (62%) patients had remained in the study and received treatment for a mean of 3.4 years. Withdrawals were for lack of efficacy (8%), adverse events (12%), and other reasons (18%). In 147 patients who completed 4 years' treatment, efficacy achieved at 6 months was maintained. At 4 years, 78%, 57%, and 31% had achieved ACR20/50/70; 43% achieved clinical remission (DAS28 <2.6); and 22% had no physical function abnormalities (HAQ = 0). Results were similar for 196 patients who received treatment for 2-4 years. Efficacy was maintained in many patients when dosages were decreased (corticosteroids (51/81 (63%) patients), MTX (92/217 (42%)), or both (25/217 (12%))). Serious adverse events were comparable during open label treatment and the controlled phase. Serious infections occurring during open label treatment and the blinded period were similar (2.03 v 2.30 events per 100 patient-years, respectively). CONCLUSIONS: Adalimumab plus MTX sustained clinical response and remission in patients with RA during 4 years. The safety profile during the first 6 months was similar to that after 4 years' follow up. Reduction of corticosteroid and/or MTX dosages did not adversely affect long term efficacy.

Pincus T, Segurado OG. · Division of Rheumatology and Immunology, Vanderbilt University School of Medicine, 203 Oxford House, Box 5, Nashville, TN 37232-4500, USA. · Ann Rheum Dis. · Pubmed #16291813 links to  free full text

Abstract: OBJECTIVE: To ask rheumatologists about the likelihood of performing a formal joint count at each visit of a patient with rheumatoid arthritis (RA) in standard clinical care. METHOD: Direct query of rheumatologists at an international meeting of about 600 rheumatologists from 17 European countries. RESULTS: Overall, 14% of rheumatologists reported performing a formal joint count at each visit of each patient, and 44% of rheumatologists reported performing a formal joint count at more than 50% of visits of patients with RA. Therefore, 56% of rheumatologists reported performing a joint count at fewer than 50% of visits, including 45% at fewer than 25% of visits. One in eight rheumatologists (13%) reported never performing a formal joint count. CONCLUSION: Although the joint count remains the most specific measure for RA, most visits of most patients with RA to most rheumatologists do not include a formal quantitative joint count.