Faculty Bibliography

Golimumab is a human anti-tumor necrosis factor (TNF)-alpha monoclonal antibody that was recently approved for the treatment of patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. This review covers the published clinical trial data on the use of golimumab for the approved indications mentioned above with respect to efficacy and safety. The various ongoing trials for golimumab have yielded promising results in terms of efficacy and safety in methotrexate-naive and -resistant patients with rheumatoid arthritis, as well as in patients who were previously treated with other anti-TNF agents. In addition, the efficacy of golimumab in psoriatic arthritis and ankylosing spondylitis has also been demonstrated. The real safety information will be available only once the drug has been used in many more patients, who frequently have comorbid conditions

ABSTRACT : Informed consent is not only for documenting a patient's acceptance of enrolling in a clinical trial. It currently is the patient's and, we propose, should also be the public's main source of information regarding the reasons for the planned study, what is known in the field about the proposed trial, and what to expect as far as efficacy and harm. Informed consent is not currently part of the clinical trial registries. For purposes of full disclosure to the patients and the public, the informed consent should be part of the required documents for such registries

Informed consent is a legal document that summarizes what will take place in a study in a language the study subjects can understand and is the process by which a person decides whether or not to participate in a study. The document is not limited to explaining the intervention or potential risks and benefits but is also the source of understanding why the study is being done and what the particular study will add to what is already known. Overall, informed consent is a document providing important transparency and clarity about the study. While consent forms are mandatory prior to study approval by internal review boards, they are not published as part of study results and are not part of clinical trial registries. The central role of an informed consent document in any study could be vitally expanded and enhanced with inclusion and full disclosure of its content through clinical trial registries and published reports in the literature, bringing improved transparency to the entire clinical trial process. Transparency is important for the maintenance of high standards in clinical research and for public trust of the process, a sometimes underrecognized factor in healthcare initiatives

A multidimensional health assessment questionnaire (MDHAQ) can enhance doctor-patient communication beyond the important function of providing RAPID3 scores, preparing the patient for the encounter and saving time for the doctor. Optimal use of the MDHAQ should include the following actions: 1. the MDHAQ should be distributed to each patient at each visit in the infrastructure of care; 2. the MDHAQ helps the patient prepare for the visit by completing it in the waiting area prior to seeing the physician; 3. the clinician prepares for the visit and saves time by reviewing the MDHAQ before seeing the patient; 4. the clinician scans the review of systems and records the number of positives on the symptom checklist; 5. the clinician reviews the recent medical history information to save time and improve accuracy and completeness of critical information; and 6. routine Assessment of Patient Index Data 3 (RAPID3) scores are recorded in the medical record and entered into a flowsheet, which also includes other MDHAQ scores, laboratory tests, and medications

Purpose: To analyze a proposed checklist of 10 quantitative measures, 6 from a patient questionnaire and 4 physician global scores, compiled in less than 20 seconds, to provide quantitative patient history and physical examination (PE) data, which rheumatologists indicate are more important than laboratory tests in clinical decisions in usual care visits. Methods: The 6 quantitative patient measures are from a self-report multidimensional health assessment questionnaire (MDHAQ) for: physical function (FN) (0-10); 21 circle 0-10 visual analog scales for pain (PN), patient global estimate (PTGL), and fatigue (FT); review of 60-symptom checklist (SX); and RAPID3, a 0-30 total of FN+PN+PTGL whcih requires 5 seconds. The 6 scores are compared on a flow sheet to scores at previous visits prior to the traditional patient encounter. The rheumatologist records 4 global estimates for: overall status (0-10), and 3 0-3 global scales for levels of inflammatory activity, joint or other organ damage, and non-inflammatory/fibromyalgia symptoms, recoded 0-10 to compare to other measures. An updated flow sheet report includes the 10 proposed checklist scores, as well as laboratory tests and medications. Mean 1st visit values for the 10 proposed checklist measures were analyzed in all 874 new patients seen at a weekly academic setting from 1996-2007 in 8 groups: rheumatoid arthritis (RA), osteoarthritis (OA), fibromyalgia (FM), systemic lupus erythematosus (SLE), gout, spondyloarthropathy (Spondy), inflammatory polyarthritis (InflPol), connective tissue disease (CTD), and other, as well as demographic data, ESR and CRP, compared using Spearman rank order correlations. Results: The 874 patients appear typical for rheumatic diseases (Table). ESR was >20 mm/Hr in RA, OA, SLE, Spondy, and CTD, while CRP was >10 mg/dL in RA and Spondy. Mean MDHAQ FN was highest in RA and also >3.0 in FM and Spondy. Mean PAIN was highest in FM, and >5 in Spondy, RA and InflPol; PTGL >5 in FM, RA and Spondy; FT >5 in FM, RA, SLE, InflPol, and other. Symptom scores were >20 only in FM. Mean MD global estimates were >=5.0 in all 8 categories - mean 5.7. Estimates were >5 for inflammation in Spondy, RA, gout, InflPol, and CTD; for damage only in RA and OA; and for noninflam/fibro symptoms in FM, SLE, and other. Quantitative demographic, laboratory tests, patient MDHAQ scores, and MD global estimates in 874 new rheumatology patients, by diagnosis, Spondy = Spondylarthropathies. InflPol = Inflammatory Polyarthritis. (Table presented) Conclusion: A proposed checklist of 10 measures, 6 from a MDHAQ and 4 global MD scores, provides quantitative data from a history and PE at each encounter in the infrastructure of rheumatology care, in <20 seconds. These data provide quantitative measures to assess patient status over long periods, treat to target values, and may lead to improved patient outcomes

Purpose: To analyze whether quantitative scores on a multidimensional health assessment questionnaire (MDHAQ) provide clues to the likelihood of inflammatory versus non-inflammatory symptoms and concomitant fibromyalgia, an important challenge in clinical care, according to a global scale for noninflammatory symptoms completed by a rheumatologist in 50 patients with SLE seen in usual care. Methods: A cross-sectional study was performed in 50 consecutive SLE patients of one rheumatologist seen in usual care. On arrival at the clinic, patients completed a multidimensional health assessment questionnaire (MDHAQ) which includes scales for physical function (FN), 0-10 visual analog scales for pain (PN), global estimate (PTGL) and fatigue (FT), and a review of systems symptom checklist (SX). SLE patients also completed a self-report Systemic Lupus Assessment Questionnaire (SLAQ). The rheumatologist, unaware of MDHAQ and SLAQ scores, recorded a physician global estimate (MDGL) and an estimate of non-inflammatory symptoms, each scored on a 0-3 scale in 0.1 increments, as well as four SLE indices: SLEDAI-2K (SLE Disease Activity Index), BILAG (British Isles Lupus Assessment Group index), SLAM (SLE Activity Measure) with and without laboratory tests, and ECLAM (European Consensus Lupus Activity Measurement). SLE patients with scores of <0.5 on the noninflammatory symptom scale were regarded as low and those with scores >=0.5 high noninflammatory symptoms; the two groups were compared using the Mann-Whitney statistic. Results: The study included 45 women and 5 men, mean age 38.7 years, mean disease duration 7.3 years. Of the 50 patients, 16 had high and 34 low scores for non-inflammatory symptoms. Those with high scores for non-inflammatory symptoms had significantly higher scores for FN, PN, FT, PTGL, SX, SLAQ, and SLAM without laboratory tests, as well as significantly lower CRP. No significant differences were seen patients estimated as high and low scoring patients for SLEDAI, BILAG, SLAM, ECLAM, C3, C4, antiDsDNA, or ESR. Fewer than 50% of low patients had FN, PN, PTGL, or FT >=2, while 100% of high patients had FT >2, and 94% PTGL >2. All patients with high non-inflammatory symptoms (16/16) reported more than 5 SX, compared to 15/34 (44%) low patients, and 12/16 (75%) high patients reported >10 SX, compared to 6/34 (18%) low patients. (Table Presented) Conclusion: High scores for dysfunction, pain, fatigue, global estimates, and number of symptoms are common in SLE patients with high versus low levels of non-inflammatory symptoms. SLE indices do not distinguish between patients with high versus low levels of non-inflammatory symptoms. A simple global scale to estimate non-inflammatory symptoms may be informative in therapeutic decisions, particularly if consistent with patient questionnaire patterns

Purpose: To analyze agreement levels between patient (PT) and physician (MD) assessments in 50 patients with SLE seen in usual care, including a) global PT and MD estimates of status; b) patient self-report scores on the SLAQ (Systemic Lupus Activity Questionnaire) and MDHAQ (Multidimensional Health Assessment Questionnaire) for physical function (FN), pain (PN), patient global estimate (PTGL), fatigue (FT), RAPID3 (FN, PN, and PTGL), and review of systems checklist (SX); c) physician-scored indices SLEDAI-2K (SLE Disease Activity Index), BILAG (British Isles Lupus Assessment Group index), SLAM (SLE Activity Measure) and ECLAM (European Consensus Lupus Activity Measurement). Methods: A cross-sectional study was performed in 50 consecutive SLE patients of one rheumatologist. Patients completed the SLAQ and MDHAQ, including PTGL. The rheumatologist scored a physician global estimate (MDGL) (scored 0-3 in 0.1 increments) without knowledge of PTGL, and completed the SLEDAI 2K, BILAG, SLAM, and ECLAM. Agreement levels of various measures were analyzed using Spearman rank order correlations. Results: The study included 45 women and 5 men, mean age 38.7 years, mean disease duration 7.3 years, 36% Caucasian, 18% Black, 26% Hispanic, 18% Asian. The mean MDGL (1.10+/-0.62), PTGL (3.11 +/-2.81) and SLE indices (SLEDAI 5.02+/-3.75; BILAG 4.60+/-4.31; SLAM 3.86+/-2.92; ECLAM 1.97+/-1.37) indicated mild/moderate lupus activity. The correlation between MDGL and PTGL of rho=0.14 was not statistically significant. Correlations between MDGL and SLE indices were significant, rho=0.60-0.72 (p<0.001). Correlations between PTGL and patient measures also were significant, rho=0.58-0.87 (p<0.001). However, PTGL was correlated at lower levels with SLE indices - significantly with BILAG and SLAM (0.35-0.40; p<0.01), and not significantly with SLEDAI or ECLAM. MDGL was not correlated significantly with any patient measure or index. (Table Presented) Conclusion: MDGL and PTGL are not correlated significantly, an observation made previously. MDGL was correlated significantly with all physician-derived indices, and PTGL was correlated significantly with all patient-derived measures and indices. By contrast, MDGL was correlated at much lower, nonsignificant levels with patient-derived measures and indices, and PTGL was correlated at lower levels with physician-derived indices. Further analysis of these discordances may clarify the clinical relevance of various measures in clinical trials, and may lead to improved care and compliance in patients with SLE

Purpose: Early and aggressive treatment of RA has been associated with improved outcomes. The objective of the Rapid Onset and Systemic Efficacy (ROSE) study was to assess the efficacy of tocilizumab (TCZ) versus placebo in combination with DMARDs in reducing signs and symptoms during 24 weeks of treatment in patients with moderate to severe RA who have had inadequate clinical response to DMARDs. Methods: 619 patients were randomly assigned to TCZ 8 mg/kg + DMARDs (TCZ, n=412) or placebo + DMARDs (control, n=207). The primary efficacy end point was ACR50 response at week 24. Efficacy parameters were assessed every 4 weeks through week 24. Disease activity was also assessed at 1 week for a subset of 62 patients. Safety and laboratory parameters were assessed throughout the study. Results: Most patients were female (81%) and Caucasian (81%); mean age was 55 y, mean disease duration was 8.6 y, mean number of previous DMARDs was 1.2, and mean DAS28 was 6.5. At week 24, there was a significantly higher percentage of ACR50 responders (primary end point) in the TCZ group than in the control group (30.1% vs 11.2%; p<0.0001). Significantly higher percentages of patients in the TCZ group than in the control group achieved ACR20 and ACR50 responses from week 4 through week 24 and ACR70 responses from week 8 through week 24 (Table). Patients in the TCZ group had significant improvement in RAPID3 scores from week 4 through week 24 and in FACIT-Fatigue scores from week 8 through week 24 compared with control (Table). In the TCZ group, improvements in CRP and Hb levels occurred early (week 4) and were sustained through week 24; CRP improvement was significant at all time points (p<0.0001). In the subset, DAS28 and patients' pain and global assessment scores significantly improved, and CRP levels normalized 1 week after TCZ treatment (p<=0.01 vs control). SAE rates/100 PY (95% CI) were 24 (17, 33) and 19 (11, 31) for the TCZ and control groups, respectively. Serious infections were reported in 2.9% and 0.5% of patients in the TCZ and control groups, respectively. Malignancies were reported in 0.7% and 1.5% of patients in the TCZ and control groups, respectively. ALT shifts from normal at baseline to >3x ULN occurred in 3.2% of TCZ patients and in 1.1% of control patients. Clinically significant (grade 3/4) decreases in neutrophil counts were reported in 2.9%/0% of TCZ patients; no grade 3/4 decreases were reported in control patients. There were no occurrences of decreased platelet counts to clinically significant values (grade 3/4). Conclusions: TCZ led to significant improvements in disease activity, ACR responses, and CRP and Hb levels as early as week 4 and in DAS28 response as early as week 1; responses persisted through week 24. Safety findings were consistent with the known safety profile of TCZ. With early and sustained efficacy, TCZ is an effective treatment option for patients with RA who have failed DMARDs. (Table Presented)