Rheumatoid Arthritis: Kivitz A

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.

Davis JC, Van Der Heijde D, Braun J, Dougados M, Cush J, Clegg DO, Kivitz A, Fleischmann R, Inman R, Tsuji W, Anonymous00203. · University of California, San Francisco, CA 94143, USA. · Arthritis Rheum. · Pubmed #14613288 links to  free full text

Abstract: OBJECTIVE: To determine the safety and efficacy of etanercept in a multicenter, randomized, placebo-controlled, double-blind trial of adults with moderate to severe active ankylosing spondylitis (AS). METHODS: Patients (n = 277) were treated with either etanercept 25 mg (n = 138) or placebo (n = 139) subcutaneously twice weekly for 24 weeks. The primary outcome measures were the percentages of patients achieving the Assessments in Ankylosing Spondylitis 20% response (ASAS20) at weeks 12 and 24. Other outcome measures included the percentage of patients achieving higher ASAS responses, and the safety of etanercept in patients with AS. All outcome measures were assessed at 2, 4, 8, 12, and 24 weeks. RESULTS: Treatment with etanercept resulted in dramatic improvement. The ASAS20 was achieved by 59% of patients in the etanercept group and by 28% of patients in the placebo group (P < 0.0001) at week 12, and by 57% and 22% of patients, respectively, at week 24 (P < 0.0001). All individual ASAS components, acute-phase reactant levels, and spinal mobility measures were also significantly improved. The safety profile of etanercept was similar to that reported in studies of patients with rheumatoid arthritis or psoriatic arthritis. The only adverse events that occurred significantly more often in the etanercept group were injection-site reactions, accidental injuries, and upper respiratory tract infections. CONCLUSION: Etanercept is a highly effective and well tolerated treatment in patients with active AS.

Kavanaugh A, Genovese M, Baughman J, Kivitz A, Bulpitt K, Olsen N, Weisman M, Matteson E, Furst D, van Vollenhoven R, Anderson J, Cohen S, Wei N, Meijerink J, Jacobs C, Mocci S. · Division of Rheumatology, Allergy and Immunology, University of California, San Diego, San Diego, CA 92037-0943, USA. · J Rheumatol. · Pubmed #12610799 No free full text.

Abstract: OBJECTIVE: Human cartilage glycoprotein 39 (HC gp-39) appears to be a relevant autoantigen in patients with rheumatoid arthritis (RA). Administration of major histocompatibility complex (MHC) Class II complexed antigens without requisite costimulatory signals can induce immunologic tolerance. We evaluated the safety, pharmacokinetics, and preliminary efficacy of AG4263 in patients with RA. AG4263 is a soluble complex of native HLA-DR4 (beta*0401) complexed to Org 36601, a 13-mer peptide derived from HC gp-39 (also referred to as CDP263). METHODS: Thirty-one HLA-DRB1*0401 positive patients with persistent RA disease activity despite concurrent methotrexate were randomized to 7 infusions of AG4263 (n = 24) or placebo (n = 7) over 6 weeks. The initial dose of 0.5 micro g/kg was escalated in subsequent cohorts to a maximum of 150 micro g/kg. Safety analyses included recording of adverse events and measurement of CD4/CD8 counts, reactivity to recall antigens, and development of antibodies to HLA-DR4. Efficacy was assessed using the Paulus 20 criteria. RESULTS: Treatment was well tolerated, with injection site reaction the most common adverse event. There was no loss of reactivity to recall antigens, change in cell counts, or antibodies to HLA-DR. The mean half-life of AG4263 was 12.5 h. Some evidence of clinical response was seen; responses were more common among patients receiving the highest doses of AG4263 and among those with baseline T cell reactivity to CDP263. CONCLUSION: AG4263 was safe, well tolerated, and without evidence of generalized immune suppression. Along with the observed trend toward clinical efficacy, the results suggest that this therapeutic approach warrants further investigation in patients with RA.

Mease PJ, Revicki DA, Szechinski J, Greenwald M, Kivitz A, Barile-Fabris L, Kalsi J, Eames J, Leirisalo-Repo M. · Seattle Rheumatology Associates, Seattle, WA 98104, USA. · J Rheumatol. · Pubmed #18050385 No free full text.

Abstract: OBJECTIVE: To evaluate the effect of rituximab treatment on health-related quality of life (HRQOL) in patients with active rheumatoid arthritis (RA), who have had an inadequate response to disease-modifying antirheumatic drugs, including biologic agents. METHODS: A randomized, multicenter, double-blind, placebo-controlled clinical trial involving 367 rheumatoid factor-positive patients was conducted. Patients received 2 infusions 2 weeks apart of placebo (n = 122), rituximab 500 mg (n = 123), or rituximab 1000 mg (n = 122), with or without glucocorticoids. All patients received stable doses of methotrexate (10 25 mg/wk). Measures included SF-36, assessed at baseline and at 24 weeks, as well as the HAQ and FACIT-Fatigue scale assessed at baseline and monthly for 24 weeks. Patients exceeding prespecified minimal clinically important differences (MCID) were examined. Clinical efficacy measurements (ACR20/50/70 and EULAR responses) were compared with HRQOL outcomes. RESULTS: At 24 weeks, the rituximab 500 mg and 1000 mg groups both reported statistically significantly greater improvements on the SF-36 physical component summary (4.37 and 4.89 points higher, respectively, vs placebo; p < 0.001). SF-36 physical function, bodily pain, vitality, social function, and role-physical subscale scores also statistically significantly improved vs placebo. At 24 weeks, 62.6% and 67.2% of the rituximab 500 mg and 1000 mg groups, respectively, exceeded the MCID of 0.22 in HAQ (p < 0.001). For FACIT-Fatigue, 55.3% and 65.6% of patients exceeded the MCID of 3.5 points compared with 35.2% of placebo over 24 weeks (p < 0.001). ACR20/50/70 and EULAR responders demonstrated greater improvements in mean baseline to 24 week changes in SF-36 and FACIT-Fatigue scores compared with nonresponders (p < 0.05). CONCLUSION: Both rituximab doses in combination with methotrexate were effective in improving all HRQOL outcomes in patients with active RA consistent with clinical efficacy.