Key clinical point: Apremilast appeared safe for long-term use with a consistent safety profile in patients with psoriatic arthritis (PsA), indicating a favorable benefit-risk profile.

Major finding: The overall incidence of serious treatment-emergent adverse events (TEAEs; exposure-adjusted incidence rate/100 patient-years, 6.9 and 8.9, respectively) and special interest TEAEs, such as major adverse cardiac events (0.1% and 0.1%, respectively), serious opportunistic infections (0.1% and 0.1%, respectively), and malignancies (0.3% and 0.4%, respectively), were similar in the apremilast and placebo groups and remained low throughout the apremilast exposure period.

Study details: This pooled analysis of 15 randomized trials included patients with plaque psoriasis (n=2,881), PsA (n=1,564), and Behçet’s syndrome (n=318) who received either apremilast or placebo.

Disclosures: This study was sponsored by Amgen Inc. Seven authors declared being employees and stockholders of Amgen. The other authors reported receiving honoraria, grants, or research funding as speakers, investigators, or advisory board members from various sources, including Amgen.

Source: Mease PJ et al. Apremilast long-term safety up to 5 years from 15 pooled randomized, placebo-controlled studies of psoriasis, psoriatic arthritis, and Behçet's syndrome. Am J Clin Dermatol. 2023;1-12 (Jun 14). Doi: 10.1007/s40257-023-00783-7.

Key clinical point: Apremilast appeared safe for long-term use with a consistent safety profile in patients with psoriatic arthritis (PsA), indicating a favorable benefit-risk profile.

Major finding: The overall incidence of serious treatment-emergent adverse events (TEAEs; exposure-adjusted incidence rate/100 patient-years, 6.9 and 8.9, respectively) and special interest TEAEs, such as major adverse cardiac events (0.1% and 0.1%, respectively), serious opportunistic infections (0.1% and 0.1%, respectively), and malignancies (0.3% and 0.4%, respectively), were similar in the apremilast and placebo groups and remained low throughout the apremilast exposure period.

Study details: This pooled analysis of 15 randomized trials included patients with plaque psoriasis (n=2,881), PsA (n=1,564), and Behçet’s syndrome (n=318) who received either apremilast or placebo.

Disclosures: This study was sponsored by Amgen Inc. Seven authors declared being employees and stockholders of Amgen. The other authors reported receiving honoraria, grants, or research funding as speakers, investigators, or advisory board members from various sources, including Amgen.

Source: Mease PJ et al. Apremilast long-term safety up to 5 years from 15 pooled randomized, placebo-controlled studies of psoriasis, psoriatic arthritis, and Behçet's syndrome. Am J Clin Dermatol. 2023;1-12 (Jun 14). Doi: 10.1007/s40257-023-00783-7.

Key clinical point: Apremilast appeared safe for long-term use with a consistent safety profile in patients with psoriatic arthritis (PsA), indicating a favorable benefit-risk profile.

Major finding: The overall incidence of serious treatment-emergent adverse events (TEAEs; exposure-adjusted incidence rate/100 patient-years, 6.9 and 8.9, respectively) and special interest TEAEs, such as major adverse cardiac events (0.1% and 0.1%, respectively), serious opportunistic infections (0.1% and 0.1%, respectively), and malignancies (0.3% and 0.4%, respectively), were similar in the apremilast and placebo groups and remained low throughout the apremilast exposure period.

Study details: This pooled analysis of 15 randomized trials included patients with plaque psoriasis (n=2,881), PsA (n=1,564), and Behçet’s syndrome (n=318) who received either apremilast or placebo.

Disclosures: This study was sponsored by Amgen Inc. Seven authors declared being employees and stockholders of Amgen. The other authors reported receiving honoraria, grants, or research funding as speakers, investigators, or advisory board members from various sources, including Amgen.

Source: Mease PJ et al. Apremilast long-term safety up to 5 years from 15 pooled randomized, placebo-controlled studies of psoriasis, psoriatic arthritis, and Behçet's syndrome. Am J Clin Dermatol. 2023;1-12 (Jun 14). Doi: 10.1007/s40257-023-00783-7.

Key clinical point: Ixekizumab improved musculoskeletal disease activity and patient-reported outcomes in a real-world cohort of patients with psoriatic arthritis.

Major finding: The Clinical Disease Activity Index improved significantly at 6 months (mean change [Δ], −3.5) and 12 months (Δ, −4.3; both P < .0001) after ixekizumab initiation, along with significant improvements in tender joint count, swollen joint count, and Physician’s Global Assessment scores (all P < .05). All patient-reported outcomes, including Patient’s Global Assessment, pain Visual Analog Scale, and Multidimensional Health Assessment Questionnaire Functional Index scores, improved at both time points.

Study details: This retrospective study included 1,812 patients with PsA from the OM1 PremiOM^TM PsA dataset who initiated ixekizumab.

Disclosures: This study was sponsored by Eli Lilly and Company Pharmaceuticals. Three authors declared being employees and shareholders of Eli Lilly and Company, and 3 other authors declared being employees of OM1, Inc. W Tillett declared being a paid consultant for various sources, including Eli Lilly. The other authors declared no conflict of interests.

Source: Tillett W et al. Changes in musculoskeletal disease activity and patient-reported outcomes in patients with psoriatic arthritis treated with ixekizumab: Results from a real-world US cohort. Front Med (Lausanne). 2023;10:1184028 (Jun 21). Doi: 10.3389/fmed.2023.1184028.

Key clinical point: Ixekizumab improved musculoskeletal disease activity and patient-reported outcomes in a real-world cohort of patients with psoriatic arthritis.

Major finding: The Clinical Disease Activity Index improved significantly at 6 months (mean change [Δ], −3.5) and 12 months (Δ, −4.3; both P < .0001) after ixekizumab initiation, along with significant improvements in tender joint count, swollen joint count, and Physician’s Global Assessment scores (all P < .05). All patient-reported outcomes, including Patient’s Global Assessment, pain Visual Analog Scale, and Multidimensional Health Assessment Questionnaire Functional Index scores, improved at both time points.

Study details: This retrospective study included 1,812 patients with PsA from the OM1 PremiOM^TM PsA dataset who initiated ixekizumab.

Disclosures: This study was sponsored by Eli Lilly and Company Pharmaceuticals. Three authors declared being employees and shareholders of Eli Lilly and Company, and 3 other authors declared being employees of OM1, Inc. W Tillett declared being a paid consultant for various sources, including Eli Lilly. The other authors declared no conflict of interests.

Source: Tillett W et al. Changes in musculoskeletal disease activity and patient-reported outcomes in patients with psoriatic arthritis treated with ixekizumab: Results from a real-world US cohort. Front Med (Lausanne). 2023;10:1184028 (Jun 21). Doi: 10.3389/fmed.2023.1184028.

Key clinical point: Ixekizumab improved musculoskeletal disease activity and patient-reported outcomes in a real-world cohort of patients with psoriatic arthritis.

Major finding: The Clinical Disease Activity Index improved significantly at 6 months (mean change [Δ], −3.5) and 12 months (Δ, −4.3; both P < .0001) after ixekizumab initiation, along with significant improvements in tender joint count, swollen joint count, and Physician’s Global Assessment scores (all P < .05). All patient-reported outcomes, including Patient’s Global Assessment, pain Visual Analog Scale, and Multidimensional Health Assessment Questionnaire Functional Index scores, improved at both time points.

Study details: This retrospective study included 1,812 patients with PsA from the OM1 PremiOM^TM PsA dataset who initiated ixekizumab.

Disclosures: This study was sponsored by Eli Lilly and Company Pharmaceuticals. Three authors declared being employees and shareholders of Eli Lilly and Company, and 3 other authors declared being employees of OM1, Inc. W Tillett declared being a paid consultant for various sources, including Eli Lilly. The other authors declared no conflict of interests.

Source: Tillett W et al. Changes in musculoskeletal disease activity and patient-reported outcomes in patients with psoriatic arthritis treated with ixekizumab: Results from a real-world US cohort. Front Med (Lausanne). 2023;10:1184028 (Jun 21). Doi: 10.3389/fmed.2023.1184028.

Key clinical point: In biologic-naïve patients with psoriatic arthritis (PsA) who initiated a first tumor necrosis factor inhibitor (TNFi), sex, disease duration, C-reactive protein level, age at treatment initiation, and fatigue predicted the achievement of the Disease Activity index for PsA in 28 joints (DAPSA28) remission at 6 months.

Major finding: Male sex (odds ratio [OR], 1.85; 95% CI, 1.54-2.23), longer disease duration (OR, 1.66; 95% CI, 1.26-2.20), and higher C-reactive protein (OR, 1.52; 95% CI, 1.22-1.89) positively predicted the achievement of DAPSA28 remission at 6 months, whereas older age at treatment initiation (OR, 0.97; 95% CI, 0.96-0.98) and higher fatigue score (OR, 0.99; 95% CI, 0.98-0.99) were negative predictors.

Study details: This study evaluated the data of 13,369 biologic-naïve patients registered with a PsA diagnosis from 13 European registries who initiated a first TNFi treatment.

Disclosures: This study was sponsored by Novartis Pharma AG. Several authors declared receiving speaker or consulting fees and research grants from various sources, including Novartis.

Source: Linde L et al. Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF inhibitor: Results from 13 European registries. Rheumatology (Oxford). 2023 (Jun 14). Doi: 10.1093/rheumatology/kead284.

Key clinical point: In biologic-naïve patients with psoriatic arthritis (PsA) who initiated a first tumor necrosis factor inhibitor (TNFi), sex, disease duration, C-reactive protein level, age at treatment initiation, and fatigue predicted the achievement of the Disease Activity index for PsA in 28 joints (DAPSA28) remission at 6 months.

Major finding: Male sex (odds ratio [OR], 1.85; 95% CI, 1.54-2.23), longer disease duration (OR, 1.66; 95% CI, 1.26-2.20), and higher C-reactive protein (OR, 1.52; 95% CI, 1.22-1.89) positively predicted the achievement of DAPSA28 remission at 6 months, whereas older age at treatment initiation (OR, 0.97; 95% CI, 0.96-0.98) and higher fatigue score (OR, 0.99; 95% CI, 0.98-0.99) were negative predictors.

Study details: This study evaluated the data of 13,369 biologic-naïve patients registered with a PsA diagnosis from 13 European registries who initiated a first TNFi treatment.

Disclosures: This study was sponsored by Novartis Pharma AG. Several authors declared receiving speaker or consulting fees and research grants from various sources, including Novartis.

Source: Linde L et al. Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF inhibitor: Results from 13 European registries. Rheumatology (Oxford). 2023 (Jun 14). Doi: 10.1093/rheumatology/kead284.

Key clinical point: In biologic-naïve patients with psoriatic arthritis (PsA) who initiated a first tumor necrosis factor inhibitor (TNFi), sex, disease duration, C-reactive protein level, age at treatment initiation, and fatigue predicted the achievement of the Disease Activity index for PsA in 28 joints (DAPSA28) remission at 6 months.

Major finding: Male sex (odds ratio [OR], 1.85; 95% CI, 1.54-2.23), longer disease duration (OR, 1.66; 95% CI, 1.26-2.20), and higher C-reactive protein (OR, 1.52; 95% CI, 1.22-1.89) positively predicted the achievement of DAPSA28 remission at 6 months, whereas older age at treatment initiation (OR, 0.97; 95% CI, 0.96-0.98) and higher fatigue score (OR, 0.99; 95% CI, 0.98-0.99) were negative predictors.

Study details: This study evaluated the data of 13,369 biologic-naïve patients registered with a PsA diagnosis from 13 European registries who initiated a first TNFi treatment.

Disclosures: This study was sponsored by Novartis Pharma AG. Several authors declared receiving speaker or consulting fees and research grants from various sources, including Novartis.

Source: Linde L et al. Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF inhibitor: Results from 13 European registries. Rheumatology (Oxford). 2023 (Jun 14). Doi: 10.1093/rheumatology/kead284.

Key clinical point: A significant quantitative association exists between baseline serum beta-defensin-2 (BD-2) levels and the clinical response to secukinumab in patients with psoriatic arthritis (PsA).

Major finding: Baseline serum BD-2 levels were significantly associated with the American College of Rheumatology (ACR) response to secukinumab (Spearman’s rho, 27%; P = 3.8e-5) but not to placebo at week 16, with the trend being consistent for ≥1 year. The addition of BD-2 to the clinical model improved the prediction of the 16-week ACR 20% improvement response to secukinumab by increasing the area under the receiver operating characteristic curve by 11 percentage points.

Study details: This retrospective analysis of the phase 3 FUTURE 1-5 trials included 1,989 patients with PsA who received secukinumab or placebo.

Disclosures: This study did not receive any funding. Seven authors declared being employees of or holding shares or stock options in Novartis AG, and M Cardner declared being an employee of AstraZeneca AB. Two authors reported ties unrelated to this study.

Source: Cardner M et al. Analysis of serum proteomics data identifies a quantitative association between beta-defensin 2 at baseline and clinical response to IL-17 blockade in psoriatic arthritis. RMD Open. 2023;9(2):e003042 (Jun 15). Doi: 10.1136/rmdopen-2023-003042.

Key clinical point: A significant quantitative association exists between baseline serum beta-defensin-2 (BD-2) levels and the clinical response to secukinumab in patients with psoriatic arthritis (PsA).

Major finding: Baseline serum BD-2 levels were significantly associated with the American College of Rheumatology (ACR) response to secukinumab (Spearman’s rho, 27%; P = 3.8e-5) but not to placebo at week 16, with the trend being consistent for ≥1 year. The addition of BD-2 to the clinical model improved the prediction of the 16-week ACR 20% improvement response to secukinumab by increasing the area under the receiver operating characteristic curve by 11 percentage points.

Study details: This retrospective analysis of the phase 3 FUTURE 1-5 trials included 1,989 patients with PsA who received secukinumab or placebo.

Disclosures: This study did not receive any funding. Seven authors declared being employees of or holding shares or stock options in Novartis AG, and M Cardner declared being an employee of AstraZeneca AB. Two authors reported ties unrelated to this study.

Source: Cardner M et al. Analysis of serum proteomics data identifies a quantitative association between beta-defensin 2 at baseline and clinical response to IL-17 blockade in psoriatic arthritis. RMD Open. 2023;9(2):e003042 (Jun 15). Doi: 10.1136/rmdopen-2023-003042.

Key clinical point: A significant quantitative association exists between baseline serum beta-defensin-2 (BD-2) levels and the clinical response to secukinumab in patients with psoriatic arthritis (PsA).

Major finding: Baseline serum BD-2 levels were significantly associated with the American College of Rheumatology (ACR) response to secukinumab (Spearman’s rho, 27%; P = 3.8e-5) but not to placebo at week 16, with the trend being consistent for ≥1 year. The addition of BD-2 to the clinical model improved the prediction of the 16-week ACR 20% improvement response to secukinumab by increasing the area under the receiver operating characteristic curve by 11 percentage points.

Study details: This retrospective analysis of the phase 3 FUTURE 1-5 trials included 1,989 patients with PsA who received secukinumab or placebo.

Disclosures: This study did not receive any funding. Seven authors declared being employees of or holding shares or stock options in Novartis AG, and M Cardner declared being an employee of AstraZeneca AB. Two authors reported ties unrelated to this study.

Source: Cardner M et al. Analysis of serum proteomics data identifies a quantitative association between beta-defensin 2 at baseline and clinical response to IL-17 blockade in psoriatic arthritis. RMD Open. 2023;9(2):e003042 (Jun 15). Doi: 10.1136/rmdopen-2023-003042.

Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.

Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.

The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”

In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”

The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
 

Study details

Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m². In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.

Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
 

Perspective

“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.

Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.

“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.

The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
 

Could colchicine help?

In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.

The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
 

Independent perspective

The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.

courtesy Banner University Medical Group–Tucson

The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.

As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
 

Takeaways

Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?

Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.

Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”

On one point all agreed: More research is needed.

Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.

Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.

Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.

The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”

In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”

The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
 

Study details

Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m². In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.

Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
 

Perspective

“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.

Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.

“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.

The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
 

Could colchicine help?

In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.

The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
 

Independent perspective

The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.

courtesy Banner University Medical Group–Tucson

The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.

As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
 

Takeaways

Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?

Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.

Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”

On one point all agreed: More research is needed.

Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.

Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.

Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.

The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”

In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”

The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
 

Study details

Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m². In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.

Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
 

Perspective

“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.

Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.

“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.

The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
 

Could colchicine help?

In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.

The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
 

Independent perspective

The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.

courtesy Banner University Medical Group–Tucson

The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.

As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
 

Takeaways

Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?

Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.

Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”

On one point all agreed: More research is needed.

Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.

New recommendations from the Joint British Thyroid Association/Society add to the increasingly general consensus that liothyronine (LT3) may be useful in combination with standard levothyroxine (LT4) in the treatment of hypothyroidism in some patients whose symptoms persist after standard treatment, despite a lack of evidence of benefit in clinical trials.

“Most patients with primary hypothyroidism respond well to levothyroxine replacement therapy,” recommends the joint association in the consensus statement, by Rupa Ahluwalia, MBBS, MD, of Norfolk and Norwich University Hospitals NHS Trust, United Kingdom, and colleagues, recently published in Clinical Endocrinology.

“For the small minority of patients who remain symptomatic despite adequate biochemical replacement with levothyroxine, a trial of liothyronine/levothyroxine combination therapy under specialist supervision may be appropriate,” they wrote.

The ongoing debate over the use of LT3/LT4 combination therapy has persisted for more than 2 decades, with at least 16 randomized controlled trials and four meta-analyses failing to show any significant benefit of the combined regimen in key quality of life and cognitive function outcomes compared with LT4 monotherapy. However, many patients continue to report benefits with combination therapy, so the issue has not been laid to rest.

Wilmar M. Wiersinga, MD, PhD, emeritus professor of endocrinology at the University of Amsterdam, said in an interview: “The scientific community is divided as to whether or not the LT4/LT3 combination therapy has any value whatsoever, whereas the pressure from individual patients and patient associations on physicians – both general practitioners and specialists/endocrinologists – can be very high [in terms of] demanding prescriptions for the combination therapy.

“I welcome this joint statement very much because it provides guidance, especially for clinicians, on a hotly debated issue,” he said.
 

Persistent symptoms drive pursuit of alternatives

T4 refers to the hormone thyroxine made in the body, and LT4 to the pharmaceutical replacement product for that hormone, levothyroxine. Similarly, T3 refers to the hormone triiodothyronine, made in the body and a precursor to thyroxine, and LT3 refers to its pharmaceutical replacement, liothyronine.

Driving the continued demand from some patients with hypothyroidism and interest among clinicians is the relatively high proportion of patients who continue to experience symptoms even after the normalization of biochemical levels after treatment with LT4, which resolves symptoms in most patients within weeks of therapy.

Those who don’t improve report common ongoing symptoms: fatigue, sleepiness, memory problems, cognitive difficulties (brain fog), and weight gain.

However, with 60% of people commonly having one or more of the same symptoms even when their thyroid levels are normal, pinpointing the actual causes is a challenge, the societies report.

In the absence of other diagnoses, clinicians often turn to alternative treatment strategies, which, as well as addition of LT3 to LT4, also include the use of desiccated thyroid extract (DTE).

DTE was the medication first used to treat hypothyroidism years ago, originally made from pig glands. There are now several prescription medications made from the desiccated (dried) thyroid glands of animals, including brands such as Armour Thyroid, NP Thyroid, and WP Thyroid.

The practice of prescribing combination therapy has already been deemed acceptable by both the European Thyroid Association (ETA) and American Thyroid Association (ATA). The latter recommended in its 2014 guidelines that the combination of LT3/LT4 therapy may be trialed in exceptional circumstances or among patients who fail to improve with LT4 alone.

In following suit, the new Joint British Thyroid Association/Society consensus statement cautions that, first and foremost, “most patients with hypothyroidism should be treated with levothyroxine alone.”

However, combination LT3/LT4 therapy may be considered an option under key important conditions, including:

• When a diagnosis of overt hypothyroidism (documented TSH ≥ 10 mU/L and/or low FT4 pretreatment with thyroid replacement hormones) is established. If overt hypothyroidism cannot be confirmed, patients are recommended to first have a trial without LT4 and a repeat serum TSH after 6 weeks.
• For patients with overt hypothyroidism, prior to consideration of LT3, the dose of LT4 should be optimized to a TSH in the target range of 0.3-2.0 mU/L for 3 to 6 months. In some patients, it may be acceptable to have serum TSH below reference range (e.g., 0.1-0.3 mU/L), but not fully suppressed in the long term, instead of starting LT3.
• A trial of combination therapy may be warranted with confirmed overt hypothyroidism and persistent symptoms despite LT4 treatment and the exclusion of other comorbidities.
• Clinicians should not feel obliged to start LT3 or continue LT3 medication provided by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest.
• When opting for LT3, a minimum of 3 to 6 months on the combination therapy should be considered before determining response to the trial, and for assessment, monitoring with serum TSH only is recommended.
• Patients should be counseled regarding the risk of arrhythmias, accelerated bone loss, and stroke associated with iatrogenic hyperthyroidism and the need for long-term monitoring.
• Given the short half-life of LT3, splitting doses across 24  hours is recommended for many people.

The joint association does not recommend the use of desiccated thyroid extract (which appears to be surprisingly on the rise, as recently reported).
 

Reasons for persistent symptoms are murky; don’t forget menopause

The key reason for the emphasis on making sure patients have overt hypothyroidism before trying LT3 is that patients are often treated with LT4 despite not even having hypothyroidism to begin with.

“In reality, many patients with subclinical hypothyroidism [TSH 5-10  mU/L] are now treated with levothyroxine, fueling a rise in its use, such that it is now the third most frequently prescribed medication in the United Kingdom,” the authors explained.

“In contrast, few patients are advised to seek lifestyle and exercise changes, despite the fact that there is positive evidence to support their benefits,” they continued.

In a recent podcast, Anthony Bianco, MD, a past president of the ATA, underscored another important factor complicating the ability to make conclusive hypothyroidism diagnoses in women: menopause.

“In my experience, the most confusing factor [in treatment decisions] is menopausal syndrome,” he said.

“The symptoms are very similar. Most patients with hypothyroidism are women. Are we getting close to menopause? Are we dealing with this? Is estrogen replacement therapy an option for this woman? Should we consult a colleague?” Dr. Bianco explained.

And there are other possibilities, including anemia, iron deficiency, other autoimmune diseases, and diabetes, he added.

“Exclude everything that you know,” Dr. Bianco said. “Use your common sense.”

Although the new statement echoes other guidelines, the recommendations are helpful amid the ever-present debate, said Dr. Wiersinga, the endocrinologist from the Netherlands.

Because of the pressure to try combination therapy, from patients and patient associations, the statement’s position that doctors must stand by their clinical judgment is important, he noted.

“I think many doctors would welcome the recommendation that doctors are not obliged to prescribe any medication that they believe is not in the patient’s best interest, and, in particular, that ‘doctors have no obligation to continue to provide prescriptions for LT3 or desiccated thyroid extract that have been started by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest,’” he asserted.

“Also, the recommendation that an endocrinologist should be involved when a trial of T3 is considered is very valuable,” he added, noting the potential scenario of patients going to a general practitioner if turned down by a specialist for LT3.

An international consensus statement published by members of the ATA, ETA, and British Thyroid Association in 2021 further set forth recommendations for the development of future trials of LT3/LT4 combination therapy to establish more conclusive guidance. 

Senior author Simon H. Pearce has reported receiving speaker fees from IBSA, Merck, Quidel, Berlin-Chemie, and consulting for Apitope/Worg and Immunovant/Roivant on issues unrelated to T3. The other authors of the consensus statement have reported no relevant financial relationships. Dr. Wiersinga has reporting consulting for Prolevi Bio.
 

A version of this article first appeared on Medscape.com.

New recommendations from the Joint British Thyroid Association/Society add to the increasingly general consensus that liothyronine (LT3) may be useful in combination with standard levothyroxine (LT4) in the treatment of hypothyroidism in some patients whose symptoms persist after standard treatment, despite a lack of evidence of benefit in clinical trials.

“Most patients with primary hypothyroidism respond well to levothyroxine replacement therapy,” recommends the joint association in the consensus statement, by Rupa Ahluwalia, MBBS, MD, of Norfolk and Norwich University Hospitals NHS Trust, United Kingdom, and colleagues, recently published in Clinical Endocrinology.

“For the small minority of patients who remain symptomatic despite adequate biochemical replacement with levothyroxine, a trial of liothyronine/levothyroxine combination therapy under specialist supervision may be appropriate,” they wrote.

The ongoing debate over the use of LT3/LT4 combination therapy has persisted for more than 2 decades, with at least 16 randomized controlled trials and four meta-analyses failing to show any significant benefit of the combined regimen in key quality of life and cognitive function outcomes compared with LT4 monotherapy. However, many patients continue to report benefits with combination therapy, so the issue has not been laid to rest.

Wilmar M. Wiersinga, MD, PhD, emeritus professor of endocrinology at the University of Amsterdam, said in an interview: “The scientific community is divided as to whether or not the LT4/LT3 combination therapy has any value whatsoever, whereas the pressure from individual patients and patient associations on physicians – both general practitioners and specialists/endocrinologists – can be very high [in terms of] demanding prescriptions for the combination therapy.

“I welcome this joint statement very much because it provides guidance, especially for clinicians, on a hotly debated issue,” he said.
 

Persistent symptoms drive pursuit of alternatives

T4 refers to the hormone thyroxine made in the body, and LT4 to the pharmaceutical replacement product for that hormone, levothyroxine. Similarly, T3 refers to the hormone triiodothyronine, made in the body and a precursor to thyroxine, and LT3 refers to its pharmaceutical replacement, liothyronine.

Driving the continued demand from some patients with hypothyroidism and interest among clinicians is the relatively high proportion of patients who continue to experience symptoms even after the normalization of biochemical levels after treatment with LT4, which resolves symptoms in most patients within weeks of therapy.

Those who don’t improve report common ongoing symptoms: fatigue, sleepiness, memory problems, cognitive difficulties (brain fog), and weight gain.

However, with 60% of people commonly having one or more of the same symptoms even when their thyroid levels are normal, pinpointing the actual causes is a challenge, the societies report.

In the absence of other diagnoses, clinicians often turn to alternative treatment strategies, which, as well as addition of LT3 to LT4, also include the use of desiccated thyroid extract (DTE).

DTE was the medication first used to treat hypothyroidism years ago, originally made from pig glands. There are now several prescription medications made from the desiccated (dried) thyroid glands of animals, including brands such as Armour Thyroid, NP Thyroid, and WP Thyroid.

The practice of prescribing combination therapy has already been deemed acceptable by both the European Thyroid Association (ETA) and American Thyroid Association (ATA). The latter recommended in its 2014 guidelines that the combination of LT3/LT4 therapy may be trialed in exceptional circumstances or among patients who fail to improve with LT4 alone.

In following suit, the new Joint British Thyroid Association/Society consensus statement cautions that, first and foremost, “most patients with hypothyroidism should be treated with levothyroxine alone.”

However, combination LT3/LT4 therapy may be considered an option under key important conditions, including:

• When a diagnosis of overt hypothyroidism (documented TSH ≥ 10 mU/L and/or low FT4 pretreatment with thyroid replacement hormones) is established. If overt hypothyroidism cannot be confirmed, patients are recommended to first have a trial without LT4 and a repeat serum TSH after 6 weeks.
• For patients with overt hypothyroidism, prior to consideration of LT3, the dose of LT4 should be optimized to a TSH in the target range of 0.3-2.0 mU/L for 3 to 6 months. In some patients, it may be acceptable to have serum TSH below reference range (e.g., 0.1-0.3 mU/L), but not fully suppressed in the long term, instead of starting LT3.
• A trial of combination therapy may be warranted with confirmed overt hypothyroidism and persistent symptoms despite LT4 treatment and the exclusion of other comorbidities.
• Clinicians should not feel obliged to start LT3 or continue LT3 medication provided by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest.
• When opting for LT3, a minimum of 3 to 6 months on the combination therapy should be considered before determining response to the trial, and for assessment, monitoring with serum TSH only is recommended.
• Patients should be counseled regarding the risk of arrhythmias, accelerated bone loss, and stroke associated with iatrogenic hyperthyroidism and the need for long-term monitoring.
• Given the short half-life of LT3, splitting doses across 24  hours is recommended for many people.

The joint association does not recommend the use of desiccated thyroid extract (which appears to be surprisingly on the rise, as recently reported).
 

Reasons for persistent symptoms are murky; don’t forget menopause

The key reason for the emphasis on making sure patients have overt hypothyroidism before trying LT3 is that patients are often treated with LT4 despite not even having hypothyroidism to begin with.

“In reality, many patients with subclinical hypothyroidism [TSH 5-10  mU/L] are now treated with levothyroxine, fueling a rise in its use, such that it is now the third most frequently prescribed medication in the United Kingdom,” the authors explained.

“In contrast, few patients are advised to seek lifestyle and exercise changes, despite the fact that there is positive evidence to support their benefits,” they continued.

In a recent podcast, Anthony Bianco, MD, a past president of the ATA, underscored another important factor complicating the ability to make conclusive hypothyroidism diagnoses in women: menopause.

“In my experience, the most confusing factor [in treatment decisions] is menopausal syndrome,” he said.

“The symptoms are very similar. Most patients with hypothyroidism are women. Are we getting close to menopause? Are we dealing with this? Is estrogen replacement therapy an option for this woman? Should we consult a colleague?” Dr. Bianco explained.

And there are other possibilities, including anemia, iron deficiency, other autoimmune diseases, and diabetes, he added.

“Exclude everything that you know,” Dr. Bianco said. “Use your common sense.”

Although the new statement echoes other guidelines, the recommendations are helpful amid the ever-present debate, said Dr. Wiersinga, the endocrinologist from the Netherlands.

Because of the pressure to try combination therapy, from patients and patient associations, the statement’s position that doctors must stand by their clinical judgment is important, he noted.

“I think many doctors would welcome the recommendation that doctors are not obliged to prescribe any medication that they believe is not in the patient’s best interest, and, in particular, that ‘doctors have no obligation to continue to provide prescriptions for LT3 or desiccated thyroid extract that have been started by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest,’” he asserted.

“Also, the recommendation that an endocrinologist should be involved when a trial of T3 is considered is very valuable,” he added, noting the potential scenario of patients going to a general practitioner if turned down by a specialist for LT3.

An international consensus statement published by members of the ATA, ETA, and British Thyroid Association in 2021 further set forth recommendations for the development of future trials of LT3/LT4 combination therapy to establish more conclusive guidance. 

Senior author Simon H. Pearce has reported receiving speaker fees from IBSA, Merck, Quidel, Berlin-Chemie, and consulting for Apitope/Worg and Immunovant/Roivant on issues unrelated to T3. The other authors of the consensus statement have reported no relevant financial relationships. Dr. Wiersinga has reporting consulting for Prolevi Bio.
 

A version of this article first appeared on Medscape.com.

New recommendations from the Joint British Thyroid Association/Society add to the increasingly general consensus that liothyronine (LT3) may be useful in combination with standard levothyroxine (LT4) in the treatment of hypothyroidism in some patients whose symptoms persist after standard treatment, despite a lack of evidence of benefit in clinical trials.

“Most patients with primary hypothyroidism respond well to levothyroxine replacement therapy,” recommends the joint association in the consensus statement, by Rupa Ahluwalia, MBBS, MD, of Norfolk and Norwich University Hospitals NHS Trust, United Kingdom, and colleagues, recently published in Clinical Endocrinology.

“For the small minority of patients who remain symptomatic despite adequate biochemical replacement with levothyroxine, a trial of liothyronine/levothyroxine combination therapy under specialist supervision may be appropriate,” they wrote.

The ongoing debate over the use of LT3/LT4 combination therapy has persisted for more than 2 decades, with at least 16 randomized controlled trials and four meta-analyses failing to show any significant benefit of the combined regimen in key quality of life and cognitive function outcomes compared with LT4 monotherapy. However, many patients continue to report benefits with combination therapy, so the issue has not been laid to rest.

Wilmar M. Wiersinga, MD, PhD, emeritus professor of endocrinology at the University of Amsterdam, said in an interview: “The scientific community is divided as to whether or not the LT4/LT3 combination therapy has any value whatsoever, whereas the pressure from individual patients and patient associations on physicians – both general practitioners and specialists/endocrinologists – can be very high [in terms of] demanding prescriptions for the combination therapy.

“I welcome this joint statement very much because it provides guidance, especially for clinicians, on a hotly debated issue,” he said.
 

Persistent symptoms drive pursuit of alternatives

T4 refers to the hormone thyroxine made in the body, and LT4 to the pharmaceutical replacement product for that hormone, levothyroxine. Similarly, T3 refers to the hormone triiodothyronine, made in the body and a precursor to thyroxine, and LT3 refers to its pharmaceutical replacement, liothyronine.

Driving the continued demand from some patients with hypothyroidism and interest among clinicians is the relatively high proportion of patients who continue to experience symptoms even after the normalization of biochemical levels after treatment with LT4, which resolves symptoms in most patients within weeks of therapy.

Those who don’t improve report common ongoing symptoms: fatigue, sleepiness, memory problems, cognitive difficulties (brain fog), and weight gain.

However, with 60% of people commonly having one or more of the same symptoms even when their thyroid levels are normal, pinpointing the actual causes is a challenge, the societies report.

In the absence of other diagnoses, clinicians often turn to alternative treatment strategies, which, as well as addition of LT3 to LT4, also include the use of desiccated thyroid extract (DTE).

DTE was the medication first used to treat hypothyroidism years ago, originally made from pig glands. There are now several prescription medications made from the desiccated (dried) thyroid glands of animals, including brands such as Armour Thyroid, NP Thyroid, and WP Thyroid.

The practice of prescribing combination therapy has already been deemed acceptable by both the European Thyroid Association (ETA) and American Thyroid Association (ATA). The latter recommended in its 2014 guidelines that the combination of LT3/LT4 therapy may be trialed in exceptional circumstances or among patients who fail to improve with LT4 alone.

In following suit, the new Joint British Thyroid Association/Society consensus statement cautions that, first and foremost, “most patients with hypothyroidism should be treated with levothyroxine alone.”

However, combination LT3/LT4 therapy may be considered an option under key important conditions, including:

• When a diagnosis of overt hypothyroidism (documented TSH ≥ 10 mU/L and/or low FT4 pretreatment with thyroid replacement hormones) is established. If overt hypothyroidism cannot be confirmed, patients are recommended to first have a trial without LT4 and a repeat serum TSH after 6 weeks.
• For patients with overt hypothyroidism, prior to consideration of LT3, the dose of LT4 should be optimized to a TSH in the target range of 0.3-2.0 mU/L for 3 to 6 months. In some patients, it may be acceptable to have serum TSH below reference range (e.g., 0.1-0.3 mU/L), but not fully suppressed in the long term, instead of starting LT3.
• A trial of combination therapy may be warranted with confirmed overt hypothyroidism and persistent symptoms despite LT4 treatment and the exclusion of other comorbidities.
• Clinicians should not feel obliged to start LT3 or continue LT3 medication provided by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest.
• When opting for LT3, a minimum of 3 to 6 months on the combination therapy should be considered before determining response to the trial, and for assessment, monitoring with serum TSH only is recommended.
• Patients should be counseled regarding the risk of arrhythmias, accelerated bone loss, and stroke associated with iatrogenic hyperthyroidism and the need for long-term monitoring.
• Given the short half-life of LT3, splitting doses across 24  hours is recommended for many people.

The joint association does not recommend the use of desiccated thyroid extract (which appears to be surprisingly on the rise, as recently reported).
 

Reasons for persistent symptoms are murky; don’t forget menopause

The key reason for the emphasis on making sure patients have overt hypothyroidism before trying LT3 is that patients are often treated with LT4 despite not even having hypothyroidism to begin with.

“In reality, many patients with subclinical hypothyroidism [TSH 5-10  mU/L] are now treated with levothyroxine, fueling a rise in its use, such that it is now the third most frequently prescribed medication in the United Kingdom,” the authors explained.

“In contrast, few patients are advised to seek lifestyle and exercise changes, despite the fact that there is positive evidence to support their benefits,” they continued.

In a recent podcast, Anthony Bianco, MD, a past president of the ATA, underscored another important factor complicating the ability to make conclusive hypothyroidism diagnoses in women: menopause.

“In my experience, the most confusing factor [in treatment decisions] is menopausal syndrome,” he said.

“The symptoms are very similar. Most patients with hypothyroidism are women. Are we getting close to menopause? Are we dealing with this? Is estrogen replacement therapy an option for this woman? Should we consult a colleague?” Dr. Bianco explained.

And there are other possibilities, including anemia, iron deficiency, other autoimmune diseases, and diabetes, he added.

“Exclude everything that you know,” Dr. Bianco said. “Use your common sense.”

Although the new statement echoes other guidelines, the recommendations are helpful amid the ever-present debate, said Dr. Wiersinga, the endocrinologist from the Netherlands.

Because of the pressure to try combination therapy, from patients and patient associations, the statement’s position that doctors must stand by their clinical judgment is important, he noted.

“I think many doctors would welcome the recommendation that doctors are not obliged to prescribe any medication that they believe is not in the patient’s best interest, and, in particular, that ‘doctors have no obligation to continue to provide prescriptions for LT3 or desiccated thyroid extract that have been started by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest,’” he asserted.

“Also, the recommendation that an endocrinologist should be involved when a trial of T3 is considered is very valuable,” he added, noting the potential scenario of patients going to a general practitioner if turned down by a specialist for LT3.

An international consensus statement published by members of the ATA, ETA, and British Thyroid Association in 2021 further set forth recommendations for the development of future trials of LT3/LT4 combination therapy to establish more conclusive guidance. 

Senior author Simon H. Pearce has reported receiving speaker fees from IBSA, Merck, Quidel, Berlin-Chemie, and consulting for Apitope/Worg and Immunovant/Roivant on issues unrelated to T3. The other authors of the consensus statement have reported no relevant financial relationships. Dr. Wiersinga has reporting consulting for Prolevi Bio.
 

A version of this article first appeared on Medscape.com.

Key clinical point: Women who survive stages I-III breast cancer (BC) may experience improved survival outcomes on adhering to a low-carbohydrate diet, particularly one that is plant-rich.

Major finding: Compared with women having the highest carbohydrate intake, lowest protein intake, and lowest fat intake after BC diagnosis, those adhering to an overall low‐carbohydrate diet (hazard ratio [HR] 0.82; P_trend = .0001) and a plant‐rich low‐carbohydrate diet (HR 0.73; P_trend <.0001) had a significantly lower risk for all-cause mortality.

Study details: Findings are from an analysis of two ongoing cohort studies, the Nurses’ Health Study (NHS) and NHS II, including 9621 women with stages I-III BC, of which 1269 women died from BC.

Disclosures: This study was sponsored by the US National Institutes of Health and University of Toronto. Two authors declared being the founder of or receiving personal fees, nonfinancial support, and grants from various sources. The other authors declared no conflicts of interest.

Source: Farvid MS et al. Associations of low-carbohydrate diets with breast cancer survival. Cancer. 2023 (Jun 10). Doi: 10.1002/cncr.34819

Key clinical point: Women who survive stages I-III breast cancer (BC) may experience improved survival outcomes on adhering to a low-carbohydrate diet, particularly one that is plant-rich.

Major finding: Compared with women having the highest carbohydrate intake, lowest protein intake, and lowest fat intake after BC diagnosis, those adhering to an overall low‐carbohydrate diet (hazard ratio [HR] 0.82; P_trend = .0001) and a plant‐rich low‐carbohydrate diet (HR 0.73; P_trend <.0001) had a significantly lower risk for all-cause mortality.

Study details: Findings are from an analysis of two ongoing cohort studies, the Nurses’ Health Study (NHS) and NHS II, including 9621 women with stages I-III BC, of which 1269 women died from BC.

Disclosures: This study was sponsored by the US National Institutes of Health and University of Toronto. Two authors declared being the founder of or receiving personal fees, nonfinancial support, and grants from various sources. The other authors declared no conflicts of interest.

Source: Farvid MS et al. Associations of low-carbohydrate diets with breast cancer survival. Cancer. 2023 (Jun 10). Doi: 10.1002/cncr.34819

Key clinical point: Women who survive stages I-III breast cancer (BC) may experience improved survival outcomes on adhering to a low-carbohydrate diet, particularly one that is plant-rich.

Major finding: Compared with women having the highest carbohydrate intake, lowest protein intake, and lowest fat intake after BC diagnosis, those adhering to an overall low‐carbohydrate diet (hazard ratio [HR] 0.82; P_trend = .0001) and a plant‐rich low‐carbohydrate diet (HR 0.73; P_trend <.0001) had a significantly lower risk for all-cause mortality.

Study details: Findings are from an analysis of two ongoing cohort studies, the Nurses’ Health Study (NHS) and NHS II, including 9621 women with stages I-III BC, of which 1269 women died from BC.

Disclosures: This study was sponsored by the US National Institutes of Health and University of Toronto. Two authors declared being the founder of or receiving personal fees, nonfinancial support, and grants from various sources. The other authors declared no conflicts of interest.

Source: Farvid MS et al. Associations of low-carbohydrate diets with breast cancer survival. Cancer. 2023 (Jun 10). Doi: 10.1002/cncr.34819

Key clinical point: The level of stromal tumor-infiltrating lymphocytes (TIL) can provide insights on disease-free survival (DFS) outcomes in human epidermal growth factor receptor 2-low-positive (HER2-low+) early-stage breast cancer (BC).

Major finding: High (>10%) vs low (≤10%) TIL levels were associated with a 53% improvement in DFS in HER2-low+ BC (hazard ratio [HR] 0.47; P = .035) and 58% improvement in DFS in hormone receptor-positive/HER2-low+ BC (HR 0.42; P = .032).

Study details: Findings are from a single-institution retrospective analysis including 1763 patients with early-stage BC who underwent surgery, of whom 429 patients were HER2+, 739 were HER2-low+, and 595 were HER2-0.

Disclosures: This study was supported by the National Natural Science Foundation of China and the Natural Science Foundation of Shandong Province. The authors declared no conflicts of interest.

Source: Sun T et al. Tumor-infiltrating lymphocytes provides recent survival information for early-stage HER2-low-positive breast cancer: A large cohort retrospective study. Front Oncol. 2023;13:1148228 (Jun 20). Doi: 10.3389/fonc.2023.1148228

Key clinical point: The level of stromal tumor-infiltrating lymphocytes (TIL) can provide insights on disease-free survival (DFS) outcomes in human epidermal growth factor receptor 2-low-positive (HER2-low+) early-stage breast cancer (BC).

Major finding: High (>10%) vs low (≤10%) TIL levels were associated with a 53% improvement in DFS in HER2-low+ BC (hazard ratio [HR] 0.47; P = .035) and 58% improvement in DFS in hormone receptor-positive/HER2-low+ BC (HR 0.42; P = .032).

Study details: Findings are from a single-institution retrospective analysis including 1763 patients with early-stage BC who underwent surgery, of whom 429 patients were HER2+, 739 were HER2-low+, and 595 were HER2-0.

Disclosures: This study was supported by the National Natural Science Foundation of China and the Natural Science Foundation of Shandong Province. The authors declared no conflicts of interest.

Source: Sun T et al. Tumor-infiltrating lymphocytes provides recent survival information for early-stage HER2-low-positive breast cancer: A large cohort retrospective study. Front Oncol. 2023;13:1148228 (Jun 20). Doi: 10.3389/fonc.2023.1148228

Key clinical point: The level of stromal tumor-infiltrating lymphocytes (TIL) can provide insights on disease-free survival (DFS) outcomes in human epidermal growth factor receptor 2-low-positive (HER2-low+) early-stage breast cancer (BC).

Major finding: High (>10%) vs low (≤10%) TIL levels were associated with a 53% improvement in DFS in HER2-low+ BC (hazard ratio [HR] 0.47; P = .035) and 58% improvement in DFS in hormone receptor-positive/HER2-low+ BC (HR 0.42; P = .032).

Study details: Findings are from a single-institution retrospective analysis including 1763 patients with early-stage BC who underwent surgery, of whom 429 patients were HER2+, 739 were HER2-low+, and 595 were HER2-0.

Disclosures: This study was supported by the National Natural Science Foundation of China and the Natural Science Foundation of Shandong Province. The authors declared no conflicts of interest.

Source: Sun T et al. Tumor-infiltrating lymphocytes provides recent survival information for early-stage HER2-low-positive breast cancer: A large cohort retrospective study. Front Oncol. 2023;13:1148228 (Jun 20). Doi: 10.3389/fonc.2023.1148228

Key clinical point: High cardiorespiratory fitness (CRF) may prevent the development of breast cancer (BC) in postmenopausal women.

Major finding: Compared with women with low-to-moderate estimated CRF, those with high eCRF had 24% lower odds of developing BC (adjusted subdistribution hazard ratio 0.76; 95% CI 0.60-0.97).

Study details: This study used the UK Biobank data to evaluate 17,840 post-menopausal women who were free of cancer and were followed for 11 years, of which 529 women developed BC.

Disclosures: This project was funded in part by the Canadian Institutes of Health Research and discretionary funds held by JD Brooks. The authors declared no conflicts of interest.

Source: Christensen RAG et al. Association between estimated cardiorespiratory fitness and breast cancer: A prospective cohort study. Br J Sports Med. 2023 (Jun 19). Doi: 10.1136/bjsports-2021-104870

Key clinical point: High cardiorespiratory fitness (CRF) may prevent the development of breast cancer (BC) in postmenopausal women.

Major finding: Compared with women with low-to-moderate estimated CRF, those with high eCRF had 24% lower odds of developing BC (adjusted subdistribution hazard ratio 0.76; 95% CI 0.60-0.97).

Study details: This study used the UK Biobank data to evaluate 17,840 post-menopausal women who were free of cancer and were followed for 11 years, of which 529 women developed BC.

Disclosures: This project was funded in part by the Canadian Institutes of Health Research and discretionary funds held by JD Brooks. The authors declared no conflicts of interest.

Source: Christensen RAG et al. Association between estimated cardiorespiratory fitness and breast cancer: A prospective cohort study. Br J Sports Med. 2023 (Jun 19). Doi: 10.1136/bjsports-2021-104870

Key clinical point: High cardiorespiratory fitness (CRF) may prevent the development of breast cancer (BC) in postmenopausal women.

Major finding: Compared with women with low-to-moderate estimated CRF, those with high eCRF had 24% lower odds of developing BC (adjusted subdistribution hazard ratio 0.76; 95% CI 0.60-0.97).

Study details: This study used the UK Biobank data to evaluate 17,840 post-menopausal women who were free of cancer and were followed for 11 years, of which 529 women developed BC.

Disclosures: This project was funded in part by the Canadian Institutes of Health Research and discretionary funds held by JD Brooks. The authors declared no conflicts of interest.

Source: Christensen RAG et al. Association between estimated cardiorespiratory fitness and breast cancer: A prospective cohort study. Br J Sports Med. 2023 (Jun 19). Doi: 10.1136/bjsports-2021-104870

Key clinical point: Breast-conserving surgery (BCS) led to similar overall survival (OS) and better disease-specific survival (DSS) outcomes compared with mastectomy in patients with stage I/II adenoid cystic carcinoma of the breast (BACC).

Major finding: The 10-year OS rates were comparable between the BCS and mastectomy groups (P = .968), whereas DSS was significantly improved in patients who underwent BCS vs mastectomy (95% vs 89%; P = .002).

Study details: Findings are from an analysis of the Surveillance, Epidemiology, and End Results Program (SEER) including 583 patients with stage I/II BACC, of whom 386 patients underwent BCS and 197 patients underwent mastectomy.

Disclosures: This study was supported by various grants from the Science and Technology Department of Henan Province, China. The authors declared no conflicts of interest.

Source: Huang T et al. Optimal surgical procedure for treating early-stage adenoid cystic carcinoma of the breast. Sci Rep. 2023;13:10222 (Jun 23). Doi: 10.1038/s41598-023-36644-w

Key clinical point: Breast-conserving surgery (BCS) led to similar overall survival (OS) and better disease-specific survival (DSS) outcomes compared with mastectomy in patients with stage I/II adenoid cystic carcinoma of the breast (BACC).

Major finding: The 10-year OS rates were comparable between the BCS and mastectomy groups (P = .968), whereas DSS was significantly improved in patients who underwent BCS vs mastectomy (95% vs 89%; P = .002).

Study details: Findings are from an analysis of the Surveillance, Epidemiology, and End Results Program (SEER) including 583 patients with stage I/II BACC, of whom 386 patients underwent BCS and 197 patients underwent mastectomy.

Disclosures: This study was supported by various grants from the Science and Technology Department of Henan Province, China. The authors declared no conflicts of interest.

Source: Huang T et al. Optimal surgical procedure for treating early-stage adenoid cystic carcinoma of the breast. Sci Rep. 2023;13:10222 (Jun 23). Doi: 10.1038/s41598-023-36644-w

Key clinical point: Breast-conserving surgery (BCS) led to similar overall survival (OS) and better disease-specific survival (DSS) outcomes compared with mastectomy in patients with stage I/II adenoid cystic carcinoma of the breast (BACC).

Major finding: The 10-year OS rates were comparable between the BCS and mastectomy groups (P = .968), whereas DSS was significantly improved in patients who underwent BCS vs mastectomy (95% vs 89%; P = .002).

Study details: Findings are from an analysis of the Surveillance, Epidemiology, and End Results Program (SEER) including 583 patients with stage I/II BACC, of whom 386 patients underwent BCS and 197 patients underwent mastectomy.

Disclosures: This study was supported by various grants from the Science and Technology Department of Henan Province, China. The authors declared no conflicts of interest.

Source: Huang T et al. Optimal surgical procedure for treating early-stage adenoid cystic carcinoma of the breast. Sci Rep. 2023;13:10222 (Jun 23). Doi: 10.1038/s41598-023-36644-w