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Stanley B Cohen,1,* Mariah Z Leach2,* 1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA; 2Mamas Facing Forward, Louisville, Colorado, USA*These authors contributed equally to this workCorrespondence: Stanley B Cohen, Email scohen@dfwra.comAbstract: This article discusses some of the queries and concerns that patients may have about initiating or switching to treatment with a biosimilar for rheumatoid arthritis following the US 2023 release of several biosimilars of the adalimumab reference product, also known by the brand name, Humira. The article also covers the difference between a generic medicine and a biosimilar, and the clinical evidence to support the safety and efficacy of adalimumab biosimilars in patients with rheumatoid arthritis.Keywords: biosimilars, interchangeability, rheumatoid arthritis

James R O’Dell,1 Stanley B Cohen,2 J Carter Thorne,3 Joel Kremer4 1Department of Rheumatology, Division of Rheumatology and Immunology, University of Nebraska Medical Center and the Omaha VA, Omaha, NE, USA; 2Department of Internal Medicine, Metroplex Clinical Research Center, University of Texas Southwestern Medical School, Dallas, TX, USA; 3Division of Rheumatology, University of Toronto, Southlake Regional Health Centre, Toronto, ON, Canada; 4The Center for Rheumatology, Albany Medical College, Albany, NY, USA Purpose: The objective of this study was to assess the treatment for patients with rheumatoid arthritis (RA) in the USA. Patients and methods: This study entailed analysis of claims data for patients with RA who initiated treatment with oral methotrexate (MTX) or a biologic in 2009 (n=48,910) or 2012 (n=107,636) and had follow-up for 4 years (2009 cohort) or 2 years (2012 cohort). Results: A biologic was initiated before MTX for 27% of the 2009 cohort and 36% of the 2012 cohort. Concomitant use of MTX and a biologic declined from 74.1% (2009 cohort) to 45.4% (2012 cohort). Conclusion: MTX is underused in the treatment of RA in the USA. Keywords: biologic, claims, methotrexate, tumor necrosis factor

Max Greenky, Steven B Cohen Department of Orthopedic Surgery, Rothman Institute, Thomas Jefferson University, Philadelphia, PA, USA Abstract: Hamstring injuries are common injuries in all levels of athletics. Hamstring injuries can cause prolonged absence from sports and have a notorious rate of reinjury. Magnetic resonance imaging (MRI) is being increasingly utilized following a hamstring injury. Physicians are being increasingly asked to utilize MRI to predict clinical outcomes, including time frame for return to play and risk of reinjury. In spite of numerous studies in this area, no clear consensus exists. The purpose of this paper is to summarize the literature and evidence regarding the role of MRI in treating hamstring injuries. Keywords: hamstring injury, MRI, return to play

Background: Superior labral anterior-posterior (SLAP) lesions are a common cause of pain and disability in athletes. Individual studies have suggested low patient satisfaction with SLAP repairs in throwing athletes in particular and it is unclear how frequently athletes return to their previous level of competetion.Questions/purposes: We systematically reviewed the literature to determine (1) patient satisfaction and (2) return to play at previous level of competition among throwing athletes compared to all athletes who underwent repair of Type II SLAP tears using various types of fixation.Methods: We searched databases for English-language articles in peer-reviewed journals from 1950 to 2010 reporting Type II SLAP repairs with 2-year followup for our systematic review. A total of 506 patients with Type II SLAP tears were reviewed from 14 studies; of these, 327 had SLAP lesions repaired by anchor, 169 by tacks, and 10 by staples. Of the 506 patients, 198 were overhead athletes with a pooled subset of 81 identified baseball players.Results: For the entire patient population, 83% had "good-to-excellent" patient satisfaction and 73% returned to their previous level of play whereas only 63% of overhead athletes returned to their previous level of play. Anchor repair in overhead athletes resulted in a higher percentage of "good-to-excellent" patient satisfaction (88% versus 74%) and a slightly higher return to play rate (63% versus 57%) compared with tack repair.Conclusions: Repair of Type II SLAP tears leads to a return to previous level of play in most patients. Overhead athletes appear to have a lower rate of return to level of previous of play. Anchor fixation appears to be the most favorable fixation in both subjective scores and return to previous level of play. [ABSTRACT FROM AUTHOR]

Background: Graft fixation during anterior cruciate ligament (ACL) reconstruction can be achieved with use of either bioabsorbable screws or metal screws. Although bioabsorbable screws and metal screws have similar fixation strengths, bioabsorbable screws eliminate the need for removal. In addition, postoperative imaging is easier to interpret when bioabsorbable screws are used. Bioabsorbable screws may be associated with an increased inflammatory response, an increased risk of screw breakage, incomplete screw absorption, or tunnel widening. We investigated the outcomes associated with the use of bioabsorbable screws as compared with metal screws for ACL reconstruction. Our hypothesis was that there is no significant difference in outcomes between these screw types for ACL reconstruction.Methods: We systematically searched electronic databases to identify randomized controlled trials in which bioabsorbable screws were compared with metal screws for ACL reconstruction. Therapeutic studies with a minimum twelve-month mean follow-up were considered for inclusion. Clinical outcomes (International Knee Documentation Committee [IKDC], Lysholm, Tegner activity scores), laxity testing, and reported complications were evaluated in the meta-analysis. Additionally, imaging assessment of tunnel widening was evaluated.Results: Eight studies matched the inclusion criteria. These studies comprised a total of 745 patients undergoing ACL reconstruction (including 378 patients managed with bioabsorbable screws and 367 patients managed with metal screws). No significant differences were identified between the two screw types with respect to IKDC, Lysholm, or Tegner activity scores or with respect to the results of laxity testing with arthrometry. The complication rates were also statistically similar in the two groups. The variability in imaging assessment of tunnel widening among the studies precluded meta-analysis.Conclusions: The clinical results associated with bioabsorbable screws and metal screws are statistically similar. Laxity evaluation demonstrated no significant differences between bioabsorbable screws and metal screws. The complication rates associated with bioabsorbable screws and metal screws were also similar. The results of this meta-analysis support the hypothesis that there are no significant differences in the outcomes associated with bioabsorbable screws as compared with metal screws for ACL reconstruction.Level Of Evidence: Therapeutic Level II. See Instructions to Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

OBJECTIVE: RANKL is essential for osteoclast development, activation, and survival. Denosumab is a fully human monoclonal IgG2 antibody that binds RANKL, inhibiting its activity. The aim of this multicenter, randomized, double-blind, placebo-controlled, phase II study was to evaluate the effects of denosumab on structural damage in patients with rheumatoid arthritis (RA) receiving methotrexate treatment. METHODS: RA patients received subcutaneous placebo (n = 75), denosumab 60 mg (n = 71), or denosumab 180 mg (n = 72) injections every 6 months for 12 months. The primary end point was the change from baseline in the magnetic resonance imaging (MRI) erosion score at 6 months. RESULTS: At 6 months, the increase in the MRI erosion score from baseline was lower in the 60-mg denosumab group (mean change 0.13; P = 0.118) and significantly lower in the 180-mg denosumab group (mean change 0.06; P = 0.007) than in the placebo group (mean change 1.75). A significant difference in the modified Sharp erosion score was observed as early as 6 months in the 180-mg denosumab group (P = 0.019) as compared with placebo, and at 12 months, both the 60-mg (P = 0.012) and the 180-mg (P = 0.007) denosumab groups were significantly different from the placebo group. Denosumab caused sustained suppression of markers of bone turnover. There was no evidence of an effect of denosumab on joint space narrowing or on measures of RA disease activity. Rates of adverse events were comparable between the denosumab and placebo groups. CONCLUSION: Addition of twice-yearly injections of denosumab to ongoing methotrexate treatment inhibited structural damage in patients with RA for up to 12 months, with no increase in the rates of adverse events as compared with placebo. [ABSTRACT FROM AUTHOR]

Smoking-related lung diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer are growing epidemics in women in the United States and elsewhere. Although some of this disturbing trend in women can be attributed to changing smoking habits, there is emerging evidence that women may be biologically more susceptible to the harmful effects of cigarette smoke than are men. Estrogen and related compounds may up-regulate the expression of cytochrome P450 (CYP) enzymes in lungs and liver, which are involved in the metabolism of various constituents of cigarette smoke. Although metabolism of foreign substances is usually beneficial in eliminating potential toxins from the body, in some instances the metabolic process can transform harmless substances into toxic chemicals through a process called metabolic bioactivation. One important xenobiotic substrate for CYP enzymes in cigarette smoke is polycyclic aromatic hydrocarbon, which in its native form is relatively harmless in small doses but upon bioactivation by CYP enzymes, can become very toxic substances for the lungs. In this article, we explore CYP and other related pathways as potential mechanisms and targets of future research and novel discoveries to curb the growing epidemic of COPD and lung cancer in women. [ABSTRACT FROM AUTHOR]

Background: The Morel-Lavallee lesion is a closed degloving injury most commonly described in the region of the hip joint after blunt trauma. It also occurs in the knee as a result of shearing trauma during football and is a distinct lesion from prepatellar bursitis and quadriceps contusion. Purpose: To review the authors' experience with Morel-Lavallee lesion of the knee in the elite contact athlete to construct a diagnostic and treatment algorithm. STUDY DESIGN: Case series; Level of evidence, 4. Methods: Twenty-seven knees in 24 players were identified from 1 National Football League team's annual injury database as having sustained a Morel-Lavallee lesion between 1993 and 2006. Their charts were retrospectively reviewed. Results: The most common mechanism of injury was a shearing blow on the playing surface (81%). The most common motion deficit was active flexion (41%). The mean time for resolution of the fluid collection and achievement of full active flexion was 16.3 days. The mean number of practices missed was 1.5. The mean number of games missed was 0.1. Fourteen knees (52%) were treated successfully with compression wrap, cryotherapy, and motion exercises. Thirteen knees (48%) were treated with at least 1 aspiration, and 6 knees (22%) were treated with multiple aspirations for recurrent serosanguineous fluid collections. In 3 cases (11%), the Morel-Lavallee lesion was successfully treated with doxycycline sclerodesis after 3 aspirations failed to resolve the recurrent fluid collections; return to play was immediate thereafter in each case. CONCLUSION: In football, Morel-Lavallee lesion of the knee usually occurs from a shearing blow from the playing field. Diagnosis is confirmed when examination reveals a large suprapatellar area of palpable fluctuance. Elite athletes are typically able to return to practice and game play long before complete resolution of the lesion. Recurrent fluid collections can occur, necessitating aspiration in approximately half the cases for successful treatment. Recalcitrant fluid collections can be safely and expeditiously treated with doxycycline sclerodesis. [ABSTRACT FROM AUTHOR]

Golimumab is a fully human antitumor necrosis factor alpha (TNF-alpha) monoclonal antibody that is being developed for intravenous and subcutaneous administration. To assess the pharmacokinetics and safety of the intravenous formulation of golimumab, 36 adult subjects with rheumatoid arthritis were randomly assigned to receive a single infusion of placebo or golimumab (0.1, 0.3, 1, 3, 6, or 10 mg/kg). Serum concentrations of golimumab were determined using a validated enzyme-linked immunosorbent assay method. In addition to the noncompartmental analysis and compartmental modeling, a population pharmacokinetics analysis using NONMEM was also conducted. Both the maximum serum concentration and the area under the serum concentrationtime curve appeared to increase in a dose-proportional manner. The median half-life ranged from 7 to 20 days. A 2-compartment population pharmacokinetic model adequately described the pharmacokinetics of golimumab. The following pharmacokinetic parameters (typical value [% coefficient of variation]) were estimated from the population pharmacokinetic model: clearance (CL: 0.40 [10.1%] L/d), volume of distribution in the central compartment (V(c): 3.07 [6.4%] L), intercompartmental clearance (Q: 0.42 [15.5%] L/d), and volume of distribution in the peripheral compartment (V(p): 3.68 [11.8%] L). Interindividual variability of the pharmacokinetic parameters was quantified for CL (44.3%), V(c) (25.5%), Q (44.6%), and V(p) (44.6%). Residual variability was estimated to be 15.0%. Body weight was found to be an important covariate on V(c). Golimumab was generally well tolerated. The pharmacokinetics of golimumab appeared to be linear over the dose range evaluated in this study. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Bisphosphonates have slowed the progression of osteoarthritis (OA) in animal models and have decreased pain in states of high bone turnover. The Knee OA Structural Arthritis (KOSTAR) study, which is the largest study to date investigating a potential structure-modifying OA drug, tested the efficacy of risedronate in providing symptom relief and slowing disease progression in patients with knee OA. METHODS: The study group comprised 2,483 patients with medial compartment knee OA and 2-4 mm of joint space width (JSW), as determined using fluoroscopically positioned, semiflexed-view radiography. Patients were enrolled in 2 parallel 2-year studies in North America and the European Union. These studies evaluated the efficacy of risedronate at dosages of 5 mg/day, 15 mg/day, 35 mg/week (in Europe), and 50 mg/week (in North America) compared with placebo in reducing signs and symptoms, as measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and patient global assessment (PGA) scores, and in slowing radiographic progression. RESULTS: A reduction of approximately 20% in signs and symptoms, as measured by WOMAC subscales and PGA scores, was observed in all groups, with no treatment effect of risedronate demonstrated. Risedronate did not significantly reduce radiographic progression as measured by decreased JSW or using a dichotomous definition of progression (joint space loss of >or=0.6 mm). Thirteen percent of patients receiving placebo demonstrated significant disease progression over 2 years. A dose-dependent reduction in the level of C-terminal crosslinking telopeptide of type II collagen, a cartilage degradation marker associated with progressive OA, was seen in patients who received risedronate. No increase in the number of adverse events was demonstrated for risedronate compared with placebo. CONCLUSION: Although risedronate (compared with placebo) did not improve signs or symptoms of OA, nor did it alter progression of OA, a reduction in the level of a marker of cartilage degradation was observed. A sustained clinically relevant improvement in signs and symptoms was observed in all treatment and placebo groups. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the efficacy and safety of treatment with rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to anti-tumor necrosis factor (anti-TNF) therapies and to explore the pharmacokinetics and pharmacodynamics of rituximab in this population. METHODS: We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the Randomized Evaluation of Long-Term Efficacy of Rituximab in RA (REFLEX) Trial, a 2-year, multicenter, randomized, double-blind, placebo-controlled, phase III study of rituximab therapy. Patients with active RA and an inadequate response to 1 or more anti-TNF agents were randomized to receive intravenous rituximab (1 course, consisting of 2 infusions of 1,000 mg each) or placebo, both with background MTX. The primary efficacy end point was a response on the American College of Rheumatology 20% improvement criteria (ACR20) at 24 weeks. Secondary end points were responses on the ACR50 and ACR70 improvement criteria, the Disease Activity Score in 28 joints, and the European League against Rheumatism (EULAR) response criteria at 24 weeks. Additional end points included scores on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire (HAQ) Disability Index (DI), and Short Form 36 (SF-36) instruments, as well as Genant-modified Sharp radiographic scores at 24 weeks. RESULTS: Patients assigned to placebo (n = 209) and rituximab (n = 311) had active, longstanding RA. At week 24, significantly more (P < 0.0001) rituximab-treated patients than placebo-treated patients demonstrated ACR20 (51% versus 18%), ACR50 (27% versus 5%), and ACR70 (12% versus 1%) responses and moderate-to-good EULAR responses (65% versus 22%). All ACR response parameters were significantly improved in rituximab-treated patients, who also had clinically meaningful improvements in fatigue, disability, and health-related quality of life (demonstrated by FACIT-F, HAQ DI, and SF-36 scores, respectively) and showed a trend toward less progression in radiographic end points. Rituximab depleted peripheral CD20+ B cells, but the mean immunoglobulin levels (IgG, IgM, and IgA) remained within normal ranges. Most adverse events occurred with the first rituximab infusion and were of mild-to-moderate severity. The rate of serious infections was 5.2 per 100 patient-years in the rituximab group and 3.7 per 100 patient-years in the placebo group. CONCLUSION: At 24 weeks, a single course of rituximab with concomitant MTX therapy provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more anti-TNF therapies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment. METHODS: This was a 2-year, multicenter, double-blind, active comparator-controlled study of 799 RA patients with active disease of < 3 years' duration who had never been treated with MTX. Treatments included adalimumab 40 mg subcutaneously every other week plus oral MTX, adalimumab 40 mg subcutaneously every other week, or weekly oral MTX. Co-primary end points at year 1 were American College of Rheumatology 50% improvement (ACR50) and mean change from baseline in the modified total Sharp score. RESULTS: Combination therapy was superior to both MTX and adalimumab monotherapy in all outcomes measured. At year 1, more patients receiving combination therapy exhibited an ACR50 response (62%) than did patients who received MTX or adalimumab monotherapy (46% and 41%, respectively; both P < 0.001). Similar superiority of combination therapy was seen in ACR20, ACR70, and ACR90 response rates at 1 and 2 years. There was significantly less radiographic progression (P < or = 0.002) among patients in the combination treatment arm at both year 1 and year 2 (1.3 and 1.9 Sharp units, respectively) than in patients in the MTX arm (5.7 and 10.4 Sharp units) or the adalimumab arm (3.0 and 5.5 Sharp units). After 2 years of treatment, 49% of patients receiving combination therapy exhibited disease remission (28-joint Disease Activity Score <2.6), and 49% exhibited a major clinical response (ACR70 response for at least 6 continuous months), rates approximately twice those found among patients receiving either monotherapy. The adverse event profiles were comparable in all 3 groups. CONCLUSION: In this population of patients with early, aggressive RA, combination therapy with adalimumab plus MTX was significantly superior to either MTX alone or adalimumab alone in improving signs and symptoms of disease, inhibiting radiographic progression, and effecting clinical remission. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Etanercept has been shown to improve the articular and cutaneous manifestations of psoriatic arthritis (PsA). In this study, we further evaluated the safety, efficacy, and effect on radiographic progression of etanercept in patients with PsA. METHODS: Patients with PsA (n = 205) were randomized to receive placebo or 25 mg etanercept subcutaneously twice weekly for 24 weeks. Patients continued to receive blind-labeled therapy in a maintenance phase until all had completed the 24-week phase, then could receive open-label etanercept in a 48-week extension. Efficacy and safety were evaluated at 4, 12, and 24 weeks and at 12-week intervals thereafter. Radiographs of the hands and wrists were assessed at baseline and 24 weeks, at entry to the open-label phase, and after 48 weeks in the study. RESULTS: Etanercept significantly reduced the signs and symptoms of PsA and psoriasis. At 12 weeks, 59% of etanercept patients met the American College of Rheumatology 20% improvement criteria for joint response, compared with 15% of placebo patients (P < 0.0001), and results were sustained at 24 and 48 weeks. At 24 weeks, 23% of etanercept patients eligible for psoriasis evaluation achieved at least 75% improvement in the Psoriasis Area and Severity Index, compared with 3% of placebo patients (P = 0.001). Radiographic disease progression was inhibited in the etanercept group at 12 months; the mean annualized rate of change in the modified total Sharp score was -0.03 unit, compared with +1.00 unit in the placebo group (P = 0.0001). Etanercept was well tolerated. CONCLUSION: Etanercept reduced joint symptoms, improved psoriatic lesions, inhibited radiographic progression, and was well tolerated in patients with PsA. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate the use of starting doses of rofecoxib and nabumetone in patients with osteoarthritis (OA) of the knee. DESIGN: A 6-week, randomized, parallel-group, double-blind, placebo-controlled study. SETTING: One hundred thirteen outpatient sites in the United States. PARTICIPANTS: A total of 1,042 male and female patients aged 40 and older with OA of the knee (>6 months). INTERVENTIONS: Rofecoxib 12.5 mg once a day (n=424), nabumetone 1,000 mg once a day (n=410), or placebo (n=208) for 6 weeks. MEASUREMENTS: The primary efficacy endpoint was patient global assessment of response to therapy (PGART) over 6 weeks, which was also specifically evaluated over the first 6 days. The main safety measure was adverse events during the 6 weeks of treatment. RESULTS: The percentage of patients with a good or excellent response to therapy as assessed using PGART at Week 6 was significantly higher with rofecoxib (55.4%) than nabumetone (47.5%; P=.018) or placebo (26.7%; P<.001 vs rofecoxib or nabumetone). Median time to first report of a good or excellent PGART response was significantly shorter in patients treated with rofecoxib (2 days) than with nabumetone (4 days, P=.002) and placebo (>5 days, P<.001) (nabumetone vs placebo; P=.007). The safety profiles of rofecoxib and nabumetone were generally similar, including gastrointestinal, hypertensive, and renal adverse events. CONCLUSION: Rofecoxib 12.5 mg daily demonstrated better efficacy over 6 weeks of treatment and quicker onset of OA efficacy over the first 6 days than nabumetone 1,000 mg daily. Both therapies were generally well tolerated. [ABSTRACT FROM AUTHOR]

To determine the geographic distribution of the newly recognized human pathogen Rickettsia parkeri, we looked for this organism in ticks from Tennessee and Georgia, USA. Using PCR and sequence analysis, we identified R. parkeri in 2 Amblyomma americanum ticks. This rickettsiosis may be underdiagnosed in the eastern United States. [ABSTRACT FROM AUTHOR]