New therapeutic strategies are urgently needed to improve clinical outcomes in patients with multiple myeloma (MM). Daratumumab is a first‐in‐class, CD38 human immunoglobulin G1κ monoclonal antibody ...approved for treatment of relapsed or refractory MM. Identification of an appropriate dose regimen for daratumumab is challenging due to its target‐mediated drug disposition, leading to time‐ and concentration‐dependent pharmacokinetics. We describe a thorough evaluation of the recommended dose regimen for daratumumab in patients with relapsed or refractory MM.
G-protein-coupled receptors (GPCRs) are one of the most attractive therapeutic target classes because of their critical roles in intracellular signaling and their clinical relevance to a variety of ...diseases, including cancer, infection and inflammation. However, high conformational variability, the small exposed area of extracellular epitopes and difficulty in the preparation of GPCR antigens have delayed both the isolation of therapeutic anti-GPCR antibodies as well as studies on the structure, function and biochemical mechanisms of GPCRs. To overcome the challenges in generating highly specific anti-GPCR antibodies with enhanced efficacy and safety, various forms of antigens have been successfully designed and employed for screening with newly emerged systems based on laboratory animal immunization and high-throughput-directed evolution.
Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of secukinumab versus adalimumab as first-line ...biological monotherapy for 52 weeks in patients with active psoriatic arthritis, with a musculoskeletal primary endpoint of American College of Rheumatology (ACR) 20 response.
This parallel-group, double-blind, active-controlled, phase-3b, multicentre (168 sites in 26 countries) trial enrolled patients aged at least 18 years with active psoriatic arthritis. Eligible patients were randomly assigned (1:1) by means of interactive response technology to receive secukinumab or adalimumab. Patients, investigators, site personnel, and those doing the assessments (except independent study drug administrators) were masked to study assignment. 300 mg secukinumab was administered subcutaneously at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 48 as a pre-filled syringe. Adalimumab was administered every 2 weeks from baseline until week 50 as 40 mg per 0·4 mL citrate free subcutaneous injection. The primary outcome was the proportion of patients with at least 20% improvement in the ACR response criteria (ACR20) at week 52. Patients were analysed according to the treatment to which they were randomly assigned. Safety analyses included all safety data reported up to and including the week 52 visit for each patient who received at least one dose of study drug. The trial is registered at ClinicalTrials.gov, NCT02745080.
Between April 3, 2017 and Aug 23, 2018, we randomly assigned 853 patients to receive secukinumab (n=426) or adalimumab (n=427). 709 (83%) of 853 patients completed week 52 of the study, of whom 691 (81%) received the last study treatment at week 50. 61 (14%) of 426 patients in the secukinumab group discontinued treatment by week 52 versus 101 (24%) of 427 patients in the adalimumab group. The primary endpoint of superiority of secukinumab versus adalimumab for ACR20 response at week 52 was not met. 67% of patients in the secukinumab group achieved an ACR20 response at week 52 versus 62% of patients in the adalimumab group (OR 1·30, 95% CI 0·98–1·72; p=0·0719). The safety profiles of secukinumab and adalimumab were consistent with previous reports. Seven (2%) of 426 patients in the secukinumab group and six (1%) of 427 patients in the adalimumab group had serious infections. One death was reported in the secukinumab group due to colon cancer and was assessed as not related to the study drug by the investigator.
Secukinumab did not meet statistical significance for superiority versus adalimumab in the primary endpoint of ACR20 response at week 52. However, secukinumab was associated with a higher treatment retention rate than adalimumab. This study provides comparative data on two biological agents with different mechanisms of action, which could help guide clinical decision making in the management of patients with psoriatic arthritis.
Novartis Pharma.
Emicizumab is a humanized bispecific antibody that mimics the cofactor function of factor VIII. In a dose-escalation study in Japanese persons with hemophilia A, including those with factor VIII ...inhibitors, emicizumab markedly reduced the number of bleeding episodes.
Hemophilia A is a serious bleeding disorder caused by a deficiency of clotting factor VIII. Approximately 50% of patients have severe hemophilia A,
1
defined as less than 1% residual factor VIII activity (<1 IU per deciliter).
2
Such patients have severe bleeding from early childhood, and without appropriate treatment, recurrent bleeding into joints can lead to irreversible hemoarthropathy.
3
,
4
Standard treatment for hemophilia A includes regular prophylaxis and episodic treatment with recombinant or plasma-derived factor VIII. The goals of prophylaxis with factor VIII are to increase factor VIII activity to at least a moderate level (1 to 5 IU per deciliter) . . .
In patients undergoing total knee replacement, a single injection of abelacimab (an antibody to factor XI) administered postoperatively was superior to standard care with enoxaparin for the ...prevention of venous thromboembolism. Bleeding events were rare.
Background
Immune checkpoint inhibitors (ICIs) targeting the PD‐1/PD‐L1 axis have changed the first‐line treatment of people with advanced non‐small cell lung cancer (NSCLC). Single‐agent ...pembrolizumab (a PD‐1 inhibitor) is currently the standard of care as monotherapy in patients with PD‐L1 expression ≥ 50%, either alone or in combination with chemotherapy when PD‐L1 expression is less than 50%. Atezolizumab (PD‐L1 inhibitor) has also been approved in combination with chemotherapy and bevacizumab (an anti‐angiogenic antibody) in first‐line NSCLC regardless of PD‐L1 expression. The combination of first‐line PD‐1/PD‐L1 inhibitors with anti‐CTLA‐4 antibodies has also been shown to improve survival compared to platinum‐based chemotherapy in advanced NSCLC, particularly in people with high tumour mutational burden (TMB). The association of ipilimumab (an anti CTLA4) and nivolumab (PD‐1 inhibitor) has been approved by the US Food and Drug Administration (FDA) in all patients with PD‐L1 expression ≥1%. Although these antibodies are currently used in clinical practice, some questions remain unanswered, such as the best‐treatment strategy, the role of different biomarkers for treatment selection and the effectiveness of immunotherapy according to specific clinical characteristics.
Objectives
Primary objective: to determine the effectiveness and safety of first‐line immune checkpoint inhibitors (ICIs), as monotherapy or in combination, compared to platinum‐based chemotherapy, with or without bevacizumab for people with advanced NSCLC, according to the level of PD‐L1 expression. Secondary objective: to maintain the currency of evidence using a living systematic review approach.
Search methods
We performed an electronic search of the main databases (Cochrane Lung Cancer Group Trial Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase) from inception until 21 October 2020 and conferences meetings from 2015 onwards.
Selection criteria
We included randomised controlled trials (RCTs) reporting on the efficacy or safety of first‐line ICI treatment for adults with advanced NSCLC who had not previously received any anticancer treatment. We included trials comparing single‐ or double‐ICI treatment to standard first‐line therapy (platinum‐based chemotherapy +/‐ bevacizumab). All data come from ‘international multicentre studies involving adults, age 18 or over, with histologically‐confirmed stage IV NSCLC who had not received any previous systemic anti‐cancer treatment for advanced disease.
Data collection and analysis
Three review authors independently assessed the search results and a fourth review author resolved any disagreements. Primary outcomes were overall survival (OS) and progression‐free survival (PFS); secondary outcomes were overall objective response rate (ORR) by RECIST v 1.1, grade 3 to 5 treatment‐related adverse events (AEs) (CTCAE v 5.0) and health‐related quality of life (HRQoL). We performed meta‐analyses where appropriate using the random‐effects model for hazard ratios (HRs) or risk ratios (RRs), with 95% confidence intervals (95% CIs), and used the I² statistic to investigate heterogeneity.
Main results
Main results
We identified 15 trials for inclusion, seven completed and eight ongoing trials. We obtained data for 5893 participants from seven trials comparing first‐line single‐ (six trials) or double‐ (two trials) agent ICI with platinum‐based chemotherapy, one trial comparing both first‐line single‐ and double‐agent ICsI with platinum‐based chemotherapy. All trials were at low risk of selection and detection bias, some were classified at high risk of performance, attrition or other source of bias. The overall certainty of evidence according to GRADE ranged from moderate‐to‐low because of risk of bias, inconsistency, or imprecision. The majority of the included trials reported their outcomes by PD‐L1 expressions, with PD‐L1 ≥ 50 being considered the most clinically useful cut‐off level for decision makers. Also, iIn order to avoid overlaps between various PDL‐1 expressions we prioritised the review outcomes according to PD‐L1 ≥ 50.
Single‐agent ICI In the PD‐L1 expression ≥ 50% group single‐agent ICI probably improved OS compared to platinum‐based chemotherapy (hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.60 to 0.76, 6 RCTs, 2111 participants, moderate‐certainty evidence). In this group, single‐agent ICI also may improve PFS (HR: 0.68, 95% CI 0.52 to 0.88, 5 RCTs, 1886 participants, low‐certainty evidence) and ORR (risk ratio (RR):1.40, 95% CI 1.12 to 1.75, 4 RCTs, 1672 participants, low‐certainty evidence). HRQoL data were available for only one study including only people with PD‐L1 expression ≥ 50%, which suggested that single‐agent ICI may improve HRQoL at 15 weeks compared to platinum‐based chemotherapy (RR: 1.51, 95% CI 1.08 to 2.10, 1 RCT, 297 participants, low‐certainty evidence). In the included studies, treatment‐related AEs were not reported according to PD‐L1 expression levels. Grade 3‐4 AEs may be less frequent with single‐agent ICI compared to platinum‐based chemotherapy (RR: 0.41, 95% CI 0.33 to 0.50, I² = 62%, 5 RCTs, 3346 participants, low‐certainty evidence).
More information about efficacy of single‐agent ICI compared to platinum‐based chemotherapy according to the level of PD‐L1 expression and to TMB status or specific clinical characteristics is available in the full text.
Double‐agent ICI Double‐ICI treatment probably prolonged OS compared to platinum‐based chemotherapy in people with PD‐L1 expression ≥50% (HR: 0.72, 95% CI 0.59 to 0.89 2 RCTs, 612 participants, moderate‐certainty evidence). Trials did not report data on HRQoL, PFS and ORR according to PD‐L1 groups. Treatment related AEs were not reported according to PD‐L1 expression levels. The frequency of grade 3‐4 AEs may not differ between double‐ICI treatment and platinum‐based chemotherapy (RR: 0.78, 95% CI 0.55 to 1.09, I² = 81%, 2 RCTs, 1869 participants, low‐certainty evidence).
More information about efficacy of double‐agent ICI according to the level of PD‐L1 expression and to TMB status is available in the full text.
Authors' conclusions
Authors' conclusions
The evidence in this review suggests that single‐agent ICI in people with NSCLC and PD‐L1 ≥50% probably leads to a higher overall survival rate and may lead to a higher progression‐free survival and overall response rate when compared to platinum‐based chemotherapy and may also lead to a lower rate of adverse events and higher HRQoL. Combined ICI in people with NSCLC and PD‐L1 ≥50% also probably leads to a higher overall survival rate when compared to platinum‐based chemotherapy, but its effect on progression‐free survival, overall response rate and HRQoL is unknown due to a lack of data. The rate of adverse events may not differ between groups.
Background
Psoriasis is an immune‐mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it ...has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head‐to‐head, which is why we chose to conduct a network meta‐analysis.
Objectives
To compare the efficacy and safety of non‐biological systemic agents, small molecules, and biologics for people with moderate‐to‐severe psoriasis using a network meta‐analysis, and to provide a ranking of these treatments according to their efficacy and safety.
Search methods
For this living systematic review we updated our searches of the following databases monthly to September 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We searched two trials registers to the same date. We checked the reference lists of included studies and relevant systematic reviews for further references to eligible RCTs.
Selection criteria
Randomised controlled trials (RCTs) of systemic treatments in adults (over 18 years of age) with moderate‐to‐severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate‐to‐severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent. The primary outcomes of this review were: the proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90 at induction phase (from 8 to 24 weeks after the randomisation), and the proportion of participants with serious adverse events (SAEs) at induction phase. We did not evaluate differences in specific adverse events.
Data collection and analysis
Several groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair‐wise and network meta‐analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the PASI 90 score) and acceptability (the inverse of serious adverse events).
We assessed the certainty of the body of evidence from the NMA for the two primary outcomes and all comparisons, according to CINeMA, as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing.
We used the surface under the cumulative ranking curve (SUCRA) to infer on treatment hierarchy: 0% (treatment is the worst for effectiveness or safety) to 100% (treatment is the best for effectiveness or safety).
Main results
We included 158 studies (18 new studies for the update) in our review (57,831 randomised participants, 67.2% men, mainly recruited from hospitals). The overall average age was 45 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo‐controlled (58%), 30% were head‐to‐head studies, and 11% were multi‐armed studies with both an active comparator and a placebo. We have assessed a total of 20 treatments. In all, 133 trials were multicentric (two to 231 centres). All but two of the outcomes included in this review were limited to the induction phase (assessment from 8 to 24 weeks after randomisation). We assessed many studies (53/158) as being at high risk of bias; 25 were at an unclear risk, and 80 at low risk. Most studies (123/158) declared funding by a pharmaceutical company, and 22 studies did not report their source of funding.
Network meta‐analysis at class level showed that all of the interventions (non‐biological systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in reaching PASI 90.
At class level, in reaching PASI 90, the biologic treatments anti‐IL17, anti‐IL12/23, anti‐IL23, and anti‐TNF alpha were significantly more effective than the small molecules and the non‐biological systemic agents.
At drug level, infliximab, ixekizumab, secukinumab, brodalumab, risankizumab and guselkumab were significantly more effective in reaching PASI 90 than ustekinumab and three anti‐TNF alpha agents: adalimumab, certolizumab, and etanercept. Ustekinumab and adalimumab were significantly more effective in reaching PASI 90 than etanercept; ustekinumab was more effective than certolizumab, and the clinical effectiveness of ustekinumab and adalimumab was similar. There was no significant difference between tofacitinib or apremilast and three non‐biological drugs: fumaric acid esters (FAEs), ciclosporin and methotrexate.
Network meta‐analysis also showed that infliximab, ixekizumab, risankizumab, bimekizumab, secukinumab, guselkumab, and brodalumab outperformed other drugs when compared to placebo in reaching PASI 90. The clinical effectiveness of these drugs was similar, except for ixekizumab which had a better chance of reaching PASI 90 compared with secukinumab, guselkumab and brodalumab. The clinical effectiveness of these seven drugs was: infliximab (versus placebo): risk ratio (RR) 50.29, 95% confidence interval (CI) 20.96 to 120.67, SUCRA = 93.6; high‐certainty evidence; ixekizumab (versus placebo): RR 32.48, 95% CI 27.13 to 38.87; SUCRA = 90.5; high‐certainty evidence; risankizumab (versus placebo): RR 28.76, 95% CI 23.96 to 34.54; SUCRA = 84.6; high‐certainty evidence; bimekizumab (versus placebo): RR 58.64, 95% CI 3.72 to 923.86; SUCRA = 81.4; high‐certainty evidence; secukinumab (versus placebo): RR 25.79, 95% CI 21.61 to 30.78; SUCRA = 76.2; high‐certainty evidence; guselkumab (versus placebo): RR 25.52, 95% CI 21.25 to 30.64; SUCRA = 75; high‐certainty evidence; and brodalumab (versus placebo): RR 23.55, 95% CI 19.48 to 28.48; SUCRA = 68.4; moderate‐certainty evidence. Conservative interpretation is warranted for the results for bimekizumab (as well as mirikizumab, tyrosine kinase 2 inhibitor, acitretin, ciclosporin, fumaric acid esters, and methotrexate), as these drugs, in the NMA, have been evaluated in few trials.
We found no significant difference between any of the interventions and the placebo for the risk of SAEs. Nevertheless, the SAE analyses were based on a very low number of events with low to moderate certainty for all the comparisons. Thus, the results have to be viewed with caution and we cannot be sure of the ranking.
For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1) the results were similar to the results for PASI 90.
Information on quality of life was often poorly reported and was absent for several of the interventions.
Authors' conclusions
Our review shows that compared to placebo, the biologics infliximab, ixekizumab, risankizumab, bimekizumab, secukinumab, guselkumab and brodalumab were the most effective treatments for achieving PASI 90 in people with moderate‐to‐severe psoriasis on the basis of moderate‐ to high‐certainty evidence. This NMA evidence is limited to induction therapy (outcomes were measured from 8 to 24 weeks after randomisation) and is not sufficient for evaluation of longer‐term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean age of 45 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice.
Another major concern is that short‐term trials provide scanty and sometimes poorly‐reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the evidence for all the interventions was of low to moderate quality. In order to provide long‐term information on the safety of the treatments included in this review, it will also be necessary to evaluate non‐randomised studies and postmarketing reports released from regulatory agencies.
In terms of future research, randomised trials directly comparing active agents are necessary once high‐quality evidence of benefit against placebo is established, including head‐to‐head trials amongst and between non‐biological systemic agents and small molecules, and between biological agents (anti‐IL17 versus anti‐IL23, anti‐IL23 versus anti‐IL12/23, anti‐TNF alpha versus anti‐IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological‐naïve participants, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium‐ and long‐term benefit and safety of the interventions and the comparative safety of different agents.
Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
All bound up: A small variant of protein A (red; see picture) was used as a biotemplate for the synthesis and biofunctionalization of gold nanoparticles (AuNPs). These functionalized AuNPs were able ...to bind to antibodies (green blocks, trastuzumab; TZ) with a defined orientation, thus showing promise as bio‐nanoparticle systems suitable for selective cell labeling by membrane‐receptor‐specific recognition.
It is important to identify factors that can reduce the incidence of immunogenicity against anti-tumor necrosis factor medication in patients with inflammatory bowel disease. The objective of our ...study was to evaluate the influence of cotreatment with immune modulators (IMs) on trough levels (TLs) and antidrug antibodies.
The records of all patients with inflammatory bowel disease at the Leiden University Medical Center who received either adalimumab or infliximab (IFX) in the year 2011 and/or 2012 (n = 352) were retrospectively evaluated about the assessment of TL and antibodies and use of IM.
Two hundred seventeen patients were included (108 patients IFX; 109 patients adalimumab). Mean TL in the IFX group was higher in the combination therapy group compared with the monotherapy group, 4.6 versus 7.5 µg/mL, P = 0.04. In the adalimumab group, the difference was not significant. In patients with IFX monotherapy, the incidence of antibody formation was higher compared with patients with combination therapy (29.8% versus 5.7%, P = 0.001). IFX patients with a suboptimal dose of IM had a higher TL compared with patients who had an optimal dose, P = 0.02. The incidence of antibody formation was lower in IFX patients who immediately started with IMs compared with patients who did not (33.3% versus 66.7%, P = 0.04).
The influence of combination therapy with IM on TL and antibodies to anti-tumor necrosis factor medication was significant for IFX-treated patients. Patients who started combination therapy immediately developed antibodies less often than patients who started later with concomitant medication.
Summary Background Unlike most chronic diseases, osteoporosis treatments are generally limited to a single drug at a fixed dose and frequency. Nonetheless, no approved therapy is able to restore ...skeletal integrity in most osteoporotic patients and the long-term use of osteoporosis drugs is controversial. Thus, many patients are treated with the sequential use of two or more therapies. The DATA study showed that combined teriparatide and denosumab increased bone mineral density more than either drug alone. Discontinuing teriparatide and denosumab, however, results in rapidly declining bone mineral density. In this DATA-Switch study, we aimed to assess the changes in bone mineral density in postmenopausal osteoporotic women who transitioned between treatments. Methods This randomised controlled trial (DATA-Switch) is a preplanned extension of the denosumab and teriparatide administration study (DATA), in which 94 postmenopausal osteoporotic women were randomly assigned to receive 24 months of teriparatide (20 mg daily), denosumab (60 mg every 6 months), or both drugs. In DATA-Switch, women originally assigned to teriparatide received denosumab (teriparatide to denosumab group), those originally assigned to denosumab received teriparatide (denosumab to teriparatide group), and those originally assigned to both received an additional 24 months of denosumab alone (combination to denosumab group). Bone mineral density at the spine, hip, and wrist were measured 6 months, 12 months, 18 months, and 24 months after the drug transitions as were biochemical markers of bone turnover. The primary endpoint was the percent change in posterior-anterior spine bone mineral density over 4 years. Between-group changes were assessed by one-way analysis of variance in our modified intention-to-treat population. This study is registered with ClinicalTrials.gov , number NCT00926380. Findings Between Sept 27, 2011, and Jan 28, 2013, eligible women from the DATA study were enrolled into DATA-Switch. Of 83 potential enrollees from the DATA study, 77 completed at least one post-baseline visit. After 48 months, the primary outcome of mean spine bone mineral density increased by 18·3% (95% CI 14·9–21·8) in 27 women in the teriparatide to denosumab group, 14·0% (10·9–17·2) in 27 women the denosumab to teriparatide group, and 16·0% (14·0–18·0) in 23 women in the combination to denosumab group, although this increase did not differ significantly between groups (for between-group comparisons, p=0·13 for the teriparatide to denosumab group vs the denosumab to teriparatide group, p=0·30 for the teriparatide to denosumab group vs the combination to denosumab group, and p=0·41 for the denosumab to teriparatide group vs the combination to denosumab group). For the bone mineral density secondary outcomes, total hip bone mineral density increased more in the teriparatide to denosumab group (6·6% 95% CI 5·3–7·9) than in the denosumab to teriparatide group (2·8% 1·3–4·2, p=0·0002), but had the greatest increase in the combination to denosumab group (8·6% 7·1–10·0; p=0·0446 vs the teriparatide to denosumab group, p<0·0001 vs the denosumab to teriparatide group). Similarly, femoral neck bone mineral density increased more in the teriparatide to denosumab group (8·3% 95% CI 6·1–10·5) and the combination to denosumab group (9·1% 6·1–12·0) than in the denosumab to teriparatide group (4·9% 2·2–7·5; p=0·0447 for teriparatide to denosumab vs denosumab to teriparatide, p=0·0336 for combination to denosumab vs denosumab to teriparatide). Differences between the combination to denosumab group and the teriparatide to denosumab group did not differ significantly (p=0·67). After 48 months, radius bone mineral density was unchanged in the teriparatide to denosumab group (0·0% 95% CI −1·3 to 1·4), whereas it decreased by −1·8% (−5·0 to 1·3) in the denosumab to teriparatide group, and increased by 2·8% (1·2–4·4) in the combination to denosumab group (p=0·0075 for the teriparatide to denosumab group vs the combination to denosumab group; p=0·0099 for the denosumab to teriparatide group vs the combination to denosumab group). One participant in the denosumab to teriparatide group had nephrolithiasis, classified as being possibly related to treatment. Interpretation In postmenopausal osteoporotic women switching from teriparatide to denosumab, bone mineral density continued to increase, whereas switching from denosumab to teriparatide results in progressive or transient bone loss. These results should be considered when choosing the initial and subsequent management of postmenopausal osteoporotic patients. Funding Amgen, Eli Lilly, and National Institutes of Health.
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