Journal of Clinical Outcomes Management

Glucocorticoid use is associated with greater mortality and cardiovascular risk in RA patients, and the associated risk is greater still in patients with RA and comorbid diabetes. The findings come from a new retrospective analysis derived from U.K. primary care records.

Although patients with diabetes actually had a lower relative risk for mortality than the nondiabetes cohort, they had a greater mortality difference because of a greater baseline risk. Ultimately, glucocorticoid (GC) use was associated with an additional 44.9 deaths per 1,000 person-years in the diabetes group, compared with 34.4 per 1,000 person-years in the RA-only group.

The study, led by Ruth Costello and William Dixon, MBBS, PhD of the University of Manchester (England), was published in BMC Rheumatology.

The findings aren’t particularly surprising, given that steroid use and diabetes have associated cardiovascular risks, and physicians generally try to reduce or eliminate their use. “There’s a group [of physicians] saying that we don’t need to use steroids at all in rheumatoid arthritis, except maybe for [a] short time at diagnosis to bridge to other therapies, or during flares,” Gordon Starkebaum, MD, professor emeritus of rheumatology at the University of Washington, Seattle, said in an interview. He recounted a session at last year’s annual meeting of the American College of Rheumatology that advocated for only injectable steroid use during flare-ups. “That was provocative,” Dr. Starkebaum said.

“It’s a retrospective study, so it has some limitations, but it provides good insight, and some substantiation to what we already think,” added Brett Smith, DO, a rheumatologist practicing in Knoxville, Tenn.

Dr. Smith suggested that the study further underscores the need to follow treat-to-target protocols in RA. He emphasized that lifetime exposure to steroids is likely the greatest concern, and that steady accumulating doses are a sign of trouble. “If you need that much steroids, you need to go up on your medication – your methotrexate, or sulfasalazine, or your biologic,” said Dr. Smith. “At least 50% of people will need a biologic to [achieve] disease control, and if you get them on it, they’re going to have better disease control, compliance is typically better, and they’re going to have less steroid exposure.”

Dr. Smith also noted that comorbid diabetes shouldn’t affect treat-to-target strategies. In fact, in such patients “you should probably be following it more tightly to reduce the cardiovascular outcomes,” he said.

The retrospective analysis included 9,085 patients with RA and with or without type 2 diabetes, with a mean follow-up of 5.2 years. They were recruited to the study between 1998 and 2011. Among patients with comorbid diabetes, those exposed to GC had a mortality of 67.4 per 1,000 person-years, compared with 22.5 among those not exposed to GC. Among those with RA alone, mortality was 44.6 versus 10.2 with and without GC exposure, respectively. Those with diabetes had a lower risk ratio for mortality (2.99 vs. 4.37), but a higher mortality difference (44.9 vs. 34.4 per 1,000 person-years).

“The increased absolute hazard for all-cause mortality indicates the greater public health impact of people with RA using GCs if they have [diabetes],” the researchers wrote. “Rheumatologists should consider [diabetes] status when prescribing GCs to patients with RA given this potential impact of GC therapy on glucose control and mortality.”

The study was limited by a lack of information on GC dose and cumulative exposure. Given its retrospective nature, the study could have been affected by confounding by indication, as well as unknown confounders.

The study was funded by the Centre for Epidemiology Versus Arthritis and the National Institute for Health Research Biomedical Research Centre. Dr. Starkebaum has no relevant financial disclosures. Dr. Smith is on the speaker’s bureau for AbbVie and serves on the company’s advisory board. He is also on the advisory boards of Regeneron and Sanofi Genzyme.

SOURCE: Costello R et al. BMC Rheumatol. 2020 Feb 19. doi: 10.1186/s41927-019-0105-4.

Glucocorticoid use is associated with greater mortality and cardiovascular risk in RA patients, and the associated risk is greater still in patients with RA and comorbid diabetes. The findings come from a new retrospective analysis derived from U.K. primary care records.

Although patients with diabetes actually had a lower relative risk for mortality than the nondiabetes cohort, they had a greater mortality difference because of a greater baseline risk. Ultimately, glucocorticoid (GC) use was associated with an additional 44.9 deaths per 1,000 person-years in the diabetes group, compared with 34.4 per 1,000 person-years in the RA-only group.

The study, led by Ruth Costello and William Dixon, MBBS, PhD of the University of Manchester (England), was published in BMC Rheumatology.

The findings aren’t particularly surprising, given that steroid use and diabetes have associated cardiovascular risks, and physicians generally try to reduce or eliminate their use. “There’s a group [of physicians] saying that we don’t need to use steroids at all in rheumatoid arthritis, except maybe for [a] short time at diagnosis to bridge to other therapies, or during flares,” Gordon Starkebaum, MD, professor emeritus of rheumatology at the University of Washington, Seattle, said in an interview. He recounted a session at last year’s annual meeting of the American College of Rheumatology that advocated for only injectable steroid use during flare-ups. “That was provocative,” Dr. Starkebaum said.

“It’s a retrospective study, so it has some limitations, but it provides good insight, and some substantiation to what we already think,” added Brett Smith, DO, a rheumatologist practicing in Knoxville, Tenn.

Dr. Smith suggested that the study further underscores the need to follow treat-to-target protocols in RA. He emphasized that lifetime exposure to steroids is likely the greatest concern, and that steady accumulating doses are a sign of trouble. “If you need that much steroids, you need to go up on your medication – your methotrexate, or sulfasalazine, or your biologic,” said Dr. Smith. “At least 50% of people will need a biologic to [achieve] disease control, and if you get them on it, they’re going to have better disease control, compliance is typically better, and they’re going to have less steroid exposure.”

Dr. Smith also noted that comorbid diabetes shouldn’t affect treat-to-target strategies. In fact, in such patients “you should probably be following it more tightly to reduce the cardiovascular outcomes,” he said.

The retrospective analysis included 9,085 patients with RA and with or without type 2 diabetes, with a mean follow-up of 5.2 years. They were recruited to the study between 1998 and 2011. Among patients with comorbid diabetes, those exposed to GC had a mortality of 67.4 per 1,000 person-years, compared with 22.5 among those not exposed to GC. Among those with RA alone, mortality was 44.6 versus 10.2 with and without GC exposure, respectively. Those with diabetes had a lower risk ratio for mortality (2.99 vs. 4.37), but a higher mortality difference (44.9 vs. 34.4 per 1,000 person-years).

“The increased absolute hazard for all-cause mortality indicates the greater public health impact of people with RA using GCs if they have [diabetes],” the researchers wrote. “Rheumatologists should consider [diabetes] status when prescribing GCs to patients with RA given this potential impact of GC therapy on glucose control and mortality.”

The study was limited by a lack of information on GC dose and cumulative exposure. Given its retrospective nature, the study could have been affected by confounding by indication, as well as unknown confounders.

The study was funded by the Centre for Epidemiology Versus Arthritis and the National Institute for Health Research Biomedical Research Centre. Dr. Starkebaum has no relevant financial disclosures. Dr. Smith is on the speaker’s bureau for AbbVie and serves on the company’s advisory board. He is also on the advisory boards of Regeneron and Sanofi Genzyme.

SOURCE: Costello R et al. BMC Rheumatol. 2020 Feb 19. doi: 10.1186/s41927-019-0105-4.

Glucocorticoid use is associated with greater mortality and cardiovascular risk in RA patients, and the associated risk is greater still in patients with RA and comorbid diabetes. The findings come from a new retrospective analysis derived from U.K. primary care records.

Although patients with diabetes actually had a lower relative risk for mortality than the nondiabetes cohort, they had a greater mortality difference because of a greater baseline risk. Ultimately, glucocorticoid (GC) use was associated with an additional 44.9 deaths per 1,000 person-years in the diabetes group, compared with 34.4 per 1,000 person-years in the RA-only group.

The study, led by Ruth Costello and William Dixon, MBBS, PhD of the University of Manchester (England), was published in BMC Rheumatology.

The findings aren’t particularly surprising, given that steroid use and diabetes have associated cardiovascular risks, and physicians generally try to reduce or eliminate their use. “There’s a group [of physicians] saying that we don’t need to use steroids at all in rheumatoid arthritis, except maybe for [a] short time at diagnosis to bridge to other therapies, or during flares,” Gordon Starkebaum, MD, professor emeritus of rheumatology at the University of Washington, Seattle, said in an interview. He recounted a session at last year’s annual meeting of the American College of Rheumatology that advocated for only injectable steroid use during flare-ups. “That was provocative,” Dr. Starkebaum said.

“It’s a retrospective study, so it has some limitations, but it provides good insight, and some substantiation to what we already think,” added Brett Smith, DO, a rheumatologist practicing in Knoxville, Tenn.

Dr. Smith suggested that the study further underscores the need to follow treat-to-target protocols in RA. He emphasized that lifetime exposure to steroids is likely the greatest concern, and that steady accumulating doses are a sign of trouble. “If you need that much steroids, you need to go up on your medication – your methotrexate, or sulfasalazine, or your biologic,” said Dr. Smith. “At least 50% of people will need a biologic to [achieve] disease control, and if you get them on it, they’re going to have better disease control, compliance is typically better, and they’re going to have less steroid exposure.”

Dr. Smith also noted that comorbid diabetes shouldn’t affect treat-to-target strategies. In fact, in such patients “you should probably be following it more tightly to reduce the cardiovascular outcomes,” he said.

The retrospective analysis included 9,085 patients with RA and with or without type 2 diabetes, with a mean follow-up of 5.2 years. They were recruited to the study between 1998 and 2011. Among patients with comorbid diabetes, those exposed to GC had a mortality of 67.4 per 1,000 person-years, compared with 22.5 among those not exposed to GC. Among those with RA alone, mortality was 44.6 versus 10.2 with and without GC exposure, respectively. Those with diabetes had a lower risk ratio for mortality (2.99 vs. 4.37), but a higher mortality difference (44.9 vs. 34.4 per 1,000 person-years).

“The increased absolute hazard for all-cause mortality indicates the greater public health impact of people with RA using GCs if they have [diabetes],” the researchers wrote. “Rheumatologists should consider [diabetes] status when prescribing GCs to patients with RA given this potential impact of GC therapy on glucose control and mortality.”

The study was limited by a lack of information on GC dose and cumulative exposure. Given its retrospective nature, the study could have been affected by confounding by indication, as well as unknown confounders.

The study was funded by the Centre for Epidemiology Versus Arthritis and the National Institute for Health Research Biomedical Research Centre. Dr. Starkebaum has no relevant financial disclosures. Dr. Smith is on the speaker’s bureau for AbbVie and serves on the company’s advisory board. He is also on the advisory boards of Regeneron and Sanofi Genzyme.

SOURCE: Costello R et al. BMC Rheumatol. 2020 Feb 19. doi: 10.1186/s41927-019-0105-4.

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

Antibiotic resistance in strains of Streptococcus pneumoniae has been rising since 2013 because of changing susceptibility profiles, based on data from 1,201 isolates collected from 448 children in primary care settings.

“New strains expressing capsular serotypes not included in the 13-valent pneumococcal conjugate vaccine are emerging to cause disease, and strains that acquire antibiotic resistance are increasing in frequency due to their survival of the fittest advantage,” wrote Ravinder Kaur, PhD, of Rochester (N.Y.) General Hospital Research Institute, and colleagues.

Similar Darwinian principles occurred after the introduction of PCV-7, the study authors added.

In a prospective cohort study published in Clinical Infectious Diseases, the researchers reviewed 1,201 isolates collected from the nasopharynx during healthy periods, and from the nasopharynx and middle ear fluid (MEF) during episodes of acute otitis media, in children aged 6-36 months who were seen in primary care settings.

The isolates were collected during 2006-2016 to reflect the pre- and post-PCV13 era. Children received PCV-7 from 2006 until April 2010, and received PCV-13 after April 2010.

Overall, the number of acute otitis media (AOM) cases caused by S. pneumoniae was not significantly different between the PCV-7 and PCV-13 eras, nor was the frequency of pneumococci identified in the nasopharynx during healthy visits and visits at the start of an AOM infection.

The researchers examined susceptibility using minimum inhibitory concentrations (MIC). During healthy visits, the MIC₅₀ of isolated pneumococci was low (no greater than 0.06 mcg/mL) for all four beta-lactam drugs tested. And it didn’t change significantly over the study years.

In contrast, among the nasopharyngeal and MEF isolates during AOM, the MIC₅₀ to penicillin, amoxicillin, ceftriaxone, and meropenem during 2013-2016 rose significantly, the investigators said.

A change in antibiotic susceptibility within a subtype also contributed to the development of PCV-13 resistance.

The study authors identified three serotypes that affected the changes in susceptibility in their study population. Serotypes 35B and 35F increased their beta-lactam resistance during 2013-2016, and serotype 11A had a higher MIC to quinolones and became more prevalent during 2013-2016. Those three serotypes accounted for most of the change in antibiotic susceptibility, the researchers said.

In addition, “the frequency of strains resistant to penicillin and amoxicillin decreased with the introduction of PCV-13, but rebounded to levels similar to those before PCV-13 introduction by 2015-2016,” the investigators noted.

The study findings were limited by several factors, including the homogeneous study population and potential lack of generalizability to other settings. In addition, the researchers did not study antibiotic consumption or antibiotic treatment failure, and they could not account for potential AOM cases that may have been treated in settings other than primary care.

However, the investigators said the results support the need for additional studies and attention to the development of the next generation of PCVs, the PCV-15 and PCV-20. Both include serotypes 22F and 33F, but neither includes 35B or 35F. The PCV-20 also includes 11A and 15B.

The study was supported in part by the National Institutes of Health and Sanofi Pasteur. Some isolates collected during the 2010-2013 time period were part of a study supported by Pfizer. The researchers had no relevant financial conflicts to disclose.

SOURCE: Kaur R et al. Clin Inf Dis. 2020 Feb 18. doi: 10.1093/cid/ciaa157.

Antibiotic resistance in strains of Streptococcus pneumoniae has been rising since 2013 because of changing susceptibility profiles, based on data from 1,201 isolates collected from 448 children in primary care settings.

“New strains expressing capsular serotypes not included in the 13-valent pneumococcal conjugate vaccine are emerging to cause disease, and strains that acquire antibiotic resistance are increasing in frequency due to their survival of the fittest advantage,” wrote Ravinder Kaur, PhD, of Rochester (N.Y.) General Hospital Research Institute, and colleagues.

Similar Darwinian principles occurred after the introduction of PCV-7, the study authors added.

In a prospective cohort study published in Clinical Infectious Diseases, the researchers reviewed 1,201 isolates collected from the nasopharynx during healthy periods, and from the nasopharynx and middle ear fluid (MEF) during episodes of acute otitis media, in children aged 6-36 months who were seen in primary care settings.

The isolates were collected during 2006-2016 to reflect the pre- and post-PCV13 era. Children received PCV-7 from 2006 until April 2010, and received PCV-13 after April 2010.

Overall, the number of acute otitis media (AOM) cases caused by S. pneumoniae was not significantly different between the PCV-7 and PCV-13 eras, nor was the frequency of pneumococci identified in the nasopharynx during healthy visits and visits at the start of an AOM infection.

The researchers examined susceptibility using minimum inhibitory concentrations (MIC). During healthy visits, the MIC₅₀ of isolated pneumococci was low (no greater than 0.06 mcg/mL) for all four beta-lactam drugs tested. And it didn’t change significantly over the study years.

In contrast, among the nasopharyngeal and MEF isolates during AOM, the MIC₅₀ to penicillin, amoxicillin, ceftriaxone, and meropenem during 2013-2016 rose significantly, the investigators said.

A change in antibiotic susceptibility within a subtype also contributed to the development of PCV-13 resistance.

The study authors identified three serotypes that affected the changes in susceptibility in their study population. Serotypes 35B and 35F increased their beta-lactam resistance during 2013-2016, and serotype 11A had a higher MIC to quinolones and became more prevalent during 2013-2016. Those three serotypes accounted for most of the change in antibiotic susceptibility, the researchers said.

In addition, “the frequency of strains resistant to penicillin and amoxicillin decreased with the introduction of PCV-13, but rebounded to levels similar to those before PCV-13 introduction by 2015-2016,” the investigators noted.

The study findings were limited by several factors, including the homogeneous study population and potential lack of generalizability to other settings. In addition, the researchers did not study antibiotic consumption or antibiotic treatment failure, and they could not account for potential AOM cases that may have been treated in settings other than primary care.

However, the investigators said the results support the need for additional studies and attention to the development of the next generation of PCVs, the PCV-15 and PCV-20. Both include serotypes 22F and 33F, but neither includes 35B or 35F. The PCV-20 also includes 11A and 15B.

The study was supported in part by the National Institutes of Health and Sanofi Pasteur. Some isolates collected during the 2010-2013 time period were part of a study supported by Pfizer. The researchers had no relevant financial conflicts to disclose.

SOURCE: Kaur R et al. Clin Inf Dis. 2020 Feb 18. doi: 10.1093/cid/ciaa157.

Antibiotic resistance in strains of Streptococcus pneumoniae has been rising since 2013 because of changing susceptibility profiles, based on data from 1,201 isolates collected from 448 children in primary care settings.

“New strains expressing capsular serotypes not included in the 13-valent pneumococcal conjugate vaccine are emerging to cause disease, and strains that acquire antibiotic resistance are increasing in frequency due to their survival of the fittest advantage,” wrote Ravinder Kaur, PhD, of Rochester (N.Y.) General Hospital Research Institute, and colleagues.

Similar Darwinian principles occurred after the introduction of PCV-7, the study authors added.

In a prospective cohort study published in Clinical Infectious Diseases, the researchers reviewed 1,201 isolates collected from the nasopharynx during healthy periods, and from the nasopharynx and middle ear fluid (MEF) during episodes of acute otitis media, in children aged 6-36 months who were seen in primary care settings.

The isolates were collected during 2006-2016 to reflect the pre- and post-PCV13 era. Children received PCV-7 from 2006 until April 2010, and received PCV-13 after April 2010.

Overall, the number of acute otitis media (AOM) cases caused by S. pneumoniae was not significantly different between the PCV-7 and PCV-13 eras, nor was the frequency of pneumococci identified in the nasopharynx during healthy visits and visits at the start of an AOM infection.

The researchers examined susceptibility using minimum inhibitory concentrations (MIC). During healthy visits, the MIC₅₀ of isolated pneumococci was low (no greater than 0.06 mcg/mL) for all four beta-lactam drugs tested. And it didn’t change significantly over the study years.

In contrast, among the nasopharyngeal and MEF isolates during AOM, the MIC₅₀ to penicillin, amoxicillin, ceftriaxone, and meropenem during 2013-2016 rose significantly, the investigators said.

A change in antibiotic susceptibility within a subtype also contributed to the development of PCV-13 resistance.

The study authors identified three serotypes that affected the changes in susceptibility in their study population. Serotypes 35B and 35F increased their beta-lactam resistance during 2013-2016, and serotype 11A had a higher MIC to quinolones and became more prevalent during 2013-2016. Those three serotypes accounted for most of the change in antibiotic susceptibility, the researchers said.

In addition, “the frequency of strains resistant to penicillin and amoxicillin decreased with the introduction of PCV-13, but rebounded to levels similar to those before PCV-13 introduction by 2015-2016,” the investigators noted.

The study findings were limited by several factors, including the homogeneous study population and potential lack of generalizability to other settings. In addition, the researchers did not study antibiotic consumption or antibiotic treatment failure, and they could not account for potential AOM cases that may have been treated in settings other than primary care.

However, the investigators said the results support the need for additional studies and attention to the development of the next generation of PCVs, the PCV-15 and PCV-20. Both include serotypes 22F and 33F, but neither includes 35B or 35F. The PCV-20 also includes 11A and 15B.

The study was supported in part by the National Institutes of Health and Sanofi Pasteur. Some isolates collected during the 2010-2013 time period were part of a study supported by Pfizer. The researchers had no relevant financial conflicts to disclose.

SOURCE: Kaur R et al. Clin Inf Dis. 2020 Feb 18. doi: 10.1093/cid/ciaa157.

The first death in the United States from the novel coronavirus (COVID-19) was a Washington state man in his 50s who had underlying health conditions, state health officials announced on Feb 29. At the same time, officials there are investigating a possible COVID-19 outbreak at a long-term care facility.

Washington state officials reported two other presumptive positive cases of COVID-19, both of whom are associated with LifeCare of Kirkland, Washington. One is a woman in her 70s who is a resident at the facility and the other is a woman in her 40s who is a health care worker at the facility.

Additionally, many residents and staff members at the facility have reported respiratory symptoms, according to Jeff Duchin, MD, health officer for public health in Seattle and King County. Among the more than 100 residents at the facility, 27 have respiratory symptoms; while among the 180 staff members, 25 have reported symptoms.

Overall, these reports bring the total number of U.S. COVID-19 cases detected by the public health system to 22, though that number is expected to climb as these investigations continue.

The general risk to the American public is still low, including residents in long-term care facilities, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during the Feb. 29 press briefing. Older people are are higher risk, however, and long-term care facilities should emphasize handwashing and the early identification of individuals with symptoms.

Dr. Duchin added that health care workers who are sick should stay home and that visitors should be screened for symptoms, the same advice offered to limit the spread of influenza at long-term care facilities.

Whitehouse.gov

The CDC briefing comes after President Trump held his own press conference at the White House where he identified the person who had died as being a woman in her 50s who was medically at risk.

During that press conference, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said that the current pattern of disease with COVID-19 suggests that 75%-80% of patients will have mild illness and recover, while 15%-20% will require advanced medical care.

For the most part, the more serious cases will occur in those who are elderly or have underlying medical conditions. There is “no indication” that individuals who recover from the virus are becoming re-infected, Dr. Fauci said.

The administration also announced a series of actions aimed at slowing the spread of the virus and responding to it. On March 2, President Trump will meet with leaders in the pharmaceutical industry at the White House to discuss vaccine development. The administration is also working to ensure an adequate supply of face masks. Vice President Mike Pence said there are currently more than 40 million masks available, but that the administration has received promises of 35 million more masks per month from manufacturers. Access to masks will be prioritized for high-risk health care workers, Vice President Pence said. “The average American does not need to go out and buy a mask,” he added.

Additionally, Vice President Pence announced new travel restrictions with Iran that would bar entry to the United States for any foreign national who visited Iran in the last 14 days. The federal government is also advising Americans not to travel to the regions in Italy and South Korea that have been most affected by COVID-19. The government is also working with officials in Italy and South Korea to conduct medical screening of anyone coming into the United States from those countries.

[email protected]

The first death in the United States from the novel coronavirus (COVID-19) was a Washington state man in his 50s who had underlying health conditions, state health officials announced on Feb 29. At the same time, officials there are investigating a possible COVID-19 outbreak at a long-term care facility.

Washington state officials reported two other presumptive positive cases of COVID-19, both of whom are associated with LifeCare of Kirkland, Washington. One is a woman in her 70s who is a resident at the facility and the other is a woman in her 40s who is a health care worker at the facility.

Additionally, many residents and staff members at the facility have reported respiratory symptoms, according to Jeff Duchin, MD, health officer for public health in Seattle and King County. Among the more than 100 residents at the facility, 27 have respiratory symptoms; while among the 180 staff members, 25 have reported symptoms.

Overall, these reports bring the total number of U.S. COVID-19 cases detected by the public health system to 22, though that number is expected to climb as these investigations continue.

The general risk to the American public is still low, including residents in long-term care facilities, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during the Feb. 29 press briefing. Older people are are higher risk, however, and long-term care facilities should emphasize handwashing and the early identification of individuals with symptoms.

Dr. Duchin added that health care workers who are sick should stay home and that visitors should be screened for symptoms, the same advice offered to limit the spread of influenza at long-term care facilities.

Whitehouse.gov

The CDC briefing comes after President Trump held his own press conference at the White House where he identified the person who had died as being a woman in her 50s who was medically at risk.

During that press conference, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said that the current pattern of disease with COVID-19 suggests that 75%-80% of patients will have mild illness and recover, while 15%-20% will require advanced medical care.

For the most part, the more serious cases will occur in those who are elderly or have underlying medical conditions. There is “no indication” that individuals who recover from the virus are becoming re-infected, Dr. Fauci said.

The administration also announced a series of actions aimed at slowing the spread of the virus and responding to it. On March 2, President Trump will meet with leaders in the pharmaceutical industry at the White House to discuss vaccine development. The administration is also working to ensure an adequate supply of face masks. Vice President Mike Pence said there are currently more than 40 million masks available, but that the administration has received promises of 35 million more masks per month from manufacturers. Access to masks will be prioritized for high-risk health care workers, Vice President Pence said. “The average American does not need to go out and buy a mask,” he added.

Additionally, Vice President Pence announced new travel restrictions with Iran that would bar entry to the United States for any foreign national who visited Iran in the last 14 days. The federal government is also advising Americans not to travel to the regions in Italy and South Korea that have been most affected by COVID-19. The government is also working with officials in Italy and South Korea to conduct medical screening of anyone coming into the United States from those countries.

[email protected]

The first death in the United States from the novel coronavirus (COVID-19) was a Washington state man in his 50s who had underlying health conditions, state health officials announced on Feb 29. At the same time, officials there are investigating a possible COVID-19 outbreak at a long-term care facility.

Washington state officials reported two other presumptive positive cases of COVID-19, both of whom are associated with LifeCare of Kirkland, Washington. One is a woman in her 70s who is a resident at the facility and the other is a woman in her 40s who is a health care worker at the facility.

Additionally, many residents and staff members at the facility have reported respiratory symptoms, according to Jeff Duchin, MD, health officer for public health in Seattle and King County. Among the more than 100 residents at the facility, 27 have respiratory symptoms; while among the 180 staff members, 25 have reported symptoms.

Overall, these reports bring the total number of U.S. COVID-19 cases detected by the public health system to 22, though that number is expected to climb as these investigations continue.

The general risk to the American public is still low, including residents in long-term care facilities, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during the Feb. 29 press briefing. Older people are are higher risk, however, and long-term care facilities should emphasize handwashing and the early identification of individuals with symptoms.

Dr. Duchin added that health care workers who are sick should stay home and that visitors should be screened for symptoms, the same advice offered to limit the spread of influenza at long-term care facilities.

Whitehouse.gov

The CDC briefing comes after President Trump held his own press conference at the White House where he identified the person who had died as being a woman in her 50s who was medically at risk.

During that press conference, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said that the current pattern of disease with COVID-19 suggests that 75%-80% of patients will have mild illness and recover, while 15%-20% will require advanced medical care.

For the most part, the more serious cases will occur in those who are elderly or have underlying medical conditions. There is “no indication” that individuals who recover from the virus are becoming re-infected, Dr. Fauci said.

The administration also announced a series of actions aimed at slowing the spread of the virus and responding to it. On March 2, President Trump will meet with leaders in the pharmaceutical industry at the White House to discuss vaccine development. The administration is also working to ensure an adequate supply of face masks. Vice President Mike Pence said there are currently more than 40 million masks available, but that the administration has received promises of 35 million more masks per month from manufacturers. Access to masks will be prioritized for high-risk health care workers, Vice President Pence said. “The average American does not need to go out and buy a mask,” he added.

Additionally, Vice President Pence announced new travel restrictions with Iran that would bar entry to the United States for any foreign national who visited Iran in the last 14 days. The federal government is also advising Americans not to travel to the regions in Italy and South Korea that have been most affected by COVID-19. The government is also working with officials in Italy and South Korea to conduct medical screening of anyone coming into the United States from those countries.

[email protected]

WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.

More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.

To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.

The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.

Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.

The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.

“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”

The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.

The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.

Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.

[email protected]

SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.

WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.

More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.

To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.

The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.

Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.

The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.

“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”

The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.

The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.

Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.

[email protected]

SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.

WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.

More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.

To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.

The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.

Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.

The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.

“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”

The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.

The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.

Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.

[email protected]

SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.

WEST PALM BEACH, FLA. – The incidence rate of many cardiovascular events is more than doubled in patients with multiple sclerosis (MS), compared with matched controls without MS, according to a study presented at ACTRIMS Forum 2020. The risk of a major adverse cardiac event (MACE) – that is, a first myocardial infarction, stroke, or cardiac arrest – is approximately twofold higher. Venous thromboembolism and peripheral vascular disease also occur at notably increased rates, reported Rebecca Persson, MPH, and colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Ms. Persson is an epidemiologist at the Boston Collaborative Drug Surveillance Program in Lexington, Mass.

Vascular comorbidities are more prevalent in patients with MS than in the general population, but few studies have reported on the incidence of cardiovascular disease after MS diagnosis. To describe rates of incident cardiovascular disease after MS diagnosis and compare them with rates in a matched population without MS, the researchers analyzed data from a U.S. Department of Defense database.

The study included a cohort of 6,406 patients with MS diagnosed and treated during Jan. 2004–Aug. 2017 who had at least one prescription for an MS disease-modifying treatment.

A cohort of 66,281 patients without MS were matched to the patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. The researchers excluded patients with a history of cardiovascular disease or select comorbidities such as dyslipidemia, atrial fibrillation, or a disorder related to peripheral vascular disease. They also excluded patients with a history of treated hypertension or treated type 2 diabetes, defined as diagnosis and treatment within 90 days of each other.

Researchers considered a patient to have a cardiovascular disease outcome – including MI, stroke, cardiac arrest, heart failure, angina or unspecified ischemic heart disease, transient ischemic attack or unspecified cerebrovascular disease, venous thromboembolism, peripheral vascular disease, pericardial disease, bradycardia or heart block, or arrhythmia other than atrial fibrillation or atrial flutter – if the disease was recorded five or more times.

The researchers followed patients from cohort entry until study outcome (separate for each outcome), loss of eligibility, death, or end of data collection. Ms. Persson and colleagues calculated incidence rates (IRs) using the Byar method and incidence rate ratios (IRRs) using Poisson regression for each outcome.

The median age at MS diagnosis or at the matched date was 38 years, and 71% were female. The median duration of record after patients entered the cohort was 7.2 years for patients with MS and 5.3 years for patients without MS.

The IRs of all cardiovascular disease types, with the exception of bradycardia or heart block, were higher for patients with MS, compared with non-MS patients, the researchers reported. Many cardiovascular disease outcomes had IRRs greater than 2. “The incidence of MI was higher among MS patients than among non-MS patients,” the researchers said (IR, 12.4 vs. 5.9 per 10,000 person-years; IRR, 2.11).

“Risk of MACE and risk of stroke were higher among MS patients than among non-MS patients,” the researchers said. Relative risks also were higher among women than among men (2.47 vs. 1.55 for MACE, and 2.19 vs. 1.71 for stroke). When the investigators performed a sensitivity analysis to address the possibility that physicians might misdiagnosis MS symptoms as stroke, the rate of stroke was attenuated among patients with MS, but remained elevated relative to the rate among patients without MS (IRR, 1.63).

The IR of venous thromboembolism was more than 2 times higher among patients with MS than among non-MS patients (38.4 vs. 15.1 per 10,000 person-years; IRR, 2.54), as was the risk of peripheral vascular disease (14.9 vs. 6.0 per 10,000 person-years; IRR, 2.49). The relative risk of peripheral vascular disease was higher in women than men, and the risk in patients with MS increased after age 40 years.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four of Ms. Persson’s coauthors are employees of BMS, and one works for a company that has a business relationship with Celgene.

[email protected]

SOURCE: Persson R et al. ACTRIMS Forum 2020. Abstract P082.

WEST PALM BEACH, FLA. – The incidence rate of many cardiovascular events is more than doubled in patients with multiple sclerosis (MS), compared with matched controls without MS, according to a study presented at ACTRIMS Forum 2020. The risk of a major adverse cardiac event (MACE) – that is, a first myocardial infarction, stroke, or cardiac arrest – is approximately twofold higher. Venous thromboembolism and peripheral vascular disease also occur at notably increased rates, reported Rebecca Persson, MPH, and colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Ms. Persson is an epidemiologist at the Boston Collaborative Drug Surveillance Program in Lexington, Mass.

Vascular comorbidities are more prevalent in patients with MS than in the general population, but few studies have reported on the incidence of cardiovascular disease after MS diagnosis. To describe rates of incident cardiovascular disease after MS diagnosis and compare them with rates in a matched population without MS, the researchers analyzed data from a U.S. Department of Defense database.

The study included a cohort of 6,406 patients with MS diagnosed and treated during Jan. 2004–Aug. 2017 who had at least one prescription for an MS disease-modifying treatment.

A cohort of 66,281 patients without MS were matched to the patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. The researchers excluded patients with a history of cardiovascular disease or select comorbidities such as dyslipidemia, atrial fibrillation, or a disorder related to peripheral vascular disease. They also excluded patients with a history of treated hypertension or treated type 2 diabetes, defined as diagnosis and treatment within 90 days of each other.

Researchers considered a patient to have a cardiovascular disease outcome – including MI, stroke, cardiac arrest, heart failure, angina or unspecified ischemic heart disease, transient ischemic attack or unspecified cerebrovascular disease, venous thromboembolism, peripheral vascular disease, pericardial disease, bradycardia or heart block, or arrhythmia other than atrial fibrillation or atrial flutter – if the disease was recorded five or more times.

The researchers followed patients from cohort entry until study outcome (separate for each outcome), loss of eligibility, death, or end of data collection. Ms. Persson and colleagues calculated incidence rates (IRs) using the Byar method and incidence rate ratios (IRRs) using Poisson regression for each outcome.

The median age at MS diagnosis or at the matched date was 38 years, and 71% were female. The median duration of record after patients entered the cohort was 7.2 years for patients with MS and 5.3 years for patients without MS.

The IRs of all cardiovascular disease types, with the exception of bradycardia or heart block, were higher for patients with MS, compared with non-MS patients, the researchers reported. Many cardiovascular disease outcomes had IRRs greater than 2. “The incidence of MI was higher among MS patients than among non-MS patients,” the researchers said (IR, 12.4 vs. 5.9 per 10,000 person-years; IRR, 2.11).

“Risk of MACE and risk of stroke were higher among MS patients than among non-MS patients,” the researchers said. Relative risks also were higher among women than among men (2.47 vs. 1.55 for MACE, and 2.19 vs. 1.71 for stroke). When the investigators performed a sensitivity analysis to address the possibility that physicians might misdiagnosis MS symptoms as stroke, the rate of stroke was attenuated among patients with MS, but remained elevated relative to the rate among patients without MS (IRR, 1.63).

The IR of venous thromboembolism was more than 2 times higher among patients with MS than among non-MS patients (38.4 vs. 15.1 per 10,000 person-years; IRR, 2.54), as was the risk of peripheral vascular disease (14.9 vs. 6.0 per 10,000 person-years; IRR, 2.49). The relative risk of peripheral vascular disease was higher in women than men, and the risk in patients with MS increased after age 40 years.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four of Ms. Persson’s coauthors are employees of BMS, and one works for a company that has a business relationship with Celgene.

[email protected]

SOURCE: Persson R et al. ACTRIMS Forum 2020. Abstract P082.

WEST PALM BEACH, FLA. – The incidence rate of many cardiovascular events is more than doubled in patients with multiple sclerosis (MS), compared with matched controls without MS, according to a study presented at ACTRIMS Forum 2020. The risk of a major adverse cardiac event (MACE) – that is, a first myocardial infarction, stroke, or cardiac arrest – is approximately twofold higher. Venous thromboembolism and peripheral vascular disease also occur at notably increased rates, reported Rebecca Persson, MPH, and colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Ms. Persson is an epidemiologist at the Boston Collaborative Drug Surveillance Program in Lexington, Mass.

Vascular comorbidities are more prevalent in patients with MS than in the general population, but few studies have reported on the incidence of cardiovascular disease after MS diagnosis. To describe rates of incident cardiovascular disease after MS diagnosis and compare them with rates in a matched population without MS, the researchers analyzed data from a U.S. Department of Defense database.

The study included a cohort of 6,406 patients with MS diagnosed and treated during Jan. 2004–Aug. 2017 who had at least one prescription for an MS disease-modifying treatment.

A cohort of 66,281 patients without MS were matched to the patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. The researchers excluded patients with a history of cardiovascular disease or select comorbidities such as dyslipidemia, atrial fibrillation, or a disorder related to peripheral vascular disease. They also excluded patients with a history of treated hypertension or treated type 2 diabetes, defined as diagnosis and treatment within 90 days of each other.

Researchers considered a patient to have a cardiovascular disease outcome – including MI, stroke, cardiac arrest, heart failure, angina or unspecified ischemic heart disease, transient ischemic attack or unspecified cerebrovascular disease, venous thromboembolism, peripheral vascular disease, pericardial disease, bradycardia or heart block, or arrhythmia other than atrial fibrillation or atrial flutter – if the disease was recorded five or more times.

The researchers followed patients from cohort entry until study outcome (separate for each outcome), loss of eligibility, death, or end of data collection. Ms. Persson and colleagues calculated incidence rates (IRs) using the Byar method and incidence rate ratios (IRRs) using Poisson regression for each outcome.

The median age at MS diagnosis or at the matched date was 38 years, and 71% were female. The median duration of record after patients entered the cohort was 7.2 years for patients with MS and 5.3 years for patients without MS.

The IRs of all cardiovascular disease types, with the exception of bradycardia or heart block, were higher for patients with MS, compared with non-MS patients, the researchers reported. Many cardiovascular disease outcomes had IRRs greater than 2. “The incidence of MI was higher among MS patients than among non-MS patients,” the researchers said (IR, 12.4 vs. 5.9 per 10,000 person-years; IRR, 2.11).

“Risk of MACE and risk of stroke were higher among MS patients than among non-MS patients,” the researchers said. Relative risks also were higher among women than among men (2.47 vs. 1.55 for MACE, and 2.19 vs. 1.71 for stroke). When the investigators performed a sensitivity analysis to address the possibility that physicians might misdiagnosis MS symptoms as stroke, the rate of stroke was attenuated among patients with MS, but remained elevated relative to the rate among patients without MS (IRR, 1.63).

The IR of venous thromboembolism was more than 2 times higher among patients with MS than among non-MS patients (38.4 vs. 15.1 per 10,000 person-years; IRR, 2.54), as was the risk of peripheral vascular disease (14.9 vs. 6.0 per 10,000 person-years; IRR, 2.49). The relative risk of peripheral vascular disease was higher in women than men, and the risk in patients with MS increased after age 40 years.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four of Ms. Persson’s coauthors are employees of BMS, and one works for a company that has a business relationship with Celgene.

[email protected]

SOURCE: Persson R et al. ACTRIMS Forum 2020. Abstract P082.

WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.

“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”

With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.

“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.

“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.

In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.

The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.

For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.

The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.

Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).

And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).

Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).

Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”

Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”

“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”

However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.

Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.

And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.

“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”

In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”

Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”

“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.

Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.

WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.

“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”

With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.

“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.

“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.

In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.

The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.

For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.

The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.

Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).

And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).

Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).

Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”

Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”

“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”

However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.

Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.

And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.

“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”

In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”

Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”

“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.

Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.

WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.

“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”

With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.

“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.

“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.

In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.

The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.

For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.

The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.

Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).

And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).

Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).

Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”

Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”

“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”

However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.

Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.

And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.

“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”

In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”

Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”

“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.

Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.

The US Food and Drug Administration (FDA) has approved rimegepant (Nurtec ODT, Biohaven), the first calcitonin gene-related peptide (CGRP) receptor antagonist available in a fast-acting orally disintegrating tablet for the acute treatment of migraine in adults.

This story first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved rimegepant (Nurtec ODT, Biohaven), the first calcitonin gene-related peptide (CGRP) receptor antagonist available in a fast-acting orally disintegrating tablet for the acute treatment of migraine in adults.

This story first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved rimegepant (Nurtec ODT, Biohaven), the first calcitonin gene-related peptide (CGRP) receptor antagonist available in a fast-acting orally disintegrating tablet for the acute treatment of migraine in adults.

This story first appeared on Medscape.com.

WEST PALM BEACH, FLA. – Patients with pediatric-onset multiple sclerosis (POMS) have less higher education and greater use of high-efficacy disease-modifying therapy (DMT), compared with patients with adult-onset MS (AOMS), according to data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Among patients with POMS, researchers also have observed an association between fatigue and mood disorders on one hand and DMT choice on the other hand. “These findings confirm the unique features of POMS and suggest that DMT choice in POMS and AOMS may influence the frequency of fatigue and mood disorders,” said Mary Rensel, MD, staff neurologist in neuroimmunology at Cleveland Clinic’s Mellen Center for MS Treatment and Research, and colleagues.

POMS is defined as MS onset before age 18, and the disease characteristics of POMS and AOMS are distinct. The former diagnosis is rare, which has limited the amount of data collected on POMS to date.

MS Partners Advancing Technology and Health Solutions (MS-PATHS), sponsored by Biogen, is a multicenter initiative in which researchers collect MS performance measures longitudinally at each patient visit. MS-PATHS data include sociodemographic information, patient-reported outcomes (PROs), functional outcomes (FOs), MS phenotype, and DMT. Using MS-PATHS data, Dr. Rensel and colleagues sought to determine differences in sociodemographics, MS phenotype, PRO, FO, and DMT among patients with POMS and between patients with POMS and those with AOMS.

The investigators analyzed data cut 9 of the MS-PATHS database for their study. They included 637 participants with POMS and matched them with patients with AOMS, based on disease duration, in a 1:5 ratio. Dr. Rensel and colleagues categorized DMTs as high, mid, or low efficacy. They calculated descriptive statistics to characterize the study population. In addition, they compared MS FOs and PROs in the matched cohort using the Wilcoxon rank-sum test. Finally, linear regression analysis allowed the investigators to identify differences in the data set, while adjusting for important covariates.

The matched cohort included 5,857 patients with AOMS and 600 patients with POMS. The patients with AOMS had an average age of 49.8 years. About 87.5% of these patients were white, and 73.5% were female. The POMS patients had an average age of 31.49 years. Overall, 76.7% of these patients were white, and 73.2% were female. Dr. Rensel and colleagues found significant differences between the two groups in age at encounter, disease duration, race, insurance, Patient Determined Disease Steps (PDDS), education, employment, FOs, PROs, and DMT.

Patients with POMS used high-efficacy DMT more frequently than those with AOMS. The rate of depression was similar between patients with AOMS and those with POMS. Depression, anxiety, and fatigue were associated with DMT potency in AOMS, and anxiety and fatigue were associated with DMT groups in POMS.

Racial differences between POMS and AOMS have been reported previously, said Dr. Rensel. First-generation immigrant children have an increased risk of POMS, compared with other children. “In our data set, we had more Asians, more blacks, and fewer Caucasians in the POMS group,” said Dr. Rensel. People from a socioeconomically challenged environment have an increased risk of POMS, and this observation may explain the difference in insurance coverage between the POMS and AOMS groups, she added. Socioeconomic challenges also may explain the difference in the rate of higher education between the two groups.

“Why were the POMS cases associated with higher-efficacy DMT when only one oral MS DMT is [Food and Drug Administration]-approved for POMS?” Dr. Rensel asked. “This is likely due to the fact that POMS cases tend to have higher disease activity with more relapses and more brain lesions, leading to the choice of higher efficacy DMTs that are currently not FDA-approved for POMS.”

These data “may help [clinicians] caring for kids and teens, especially non-Caucasian [patients], to consider MS on the differential diagnosis,” Dr. Rensel added. “Mood disorders in POMS were as common as mood disorders in AOMS, so these should be screened for in this POMS population.”

Dr. Rensel has received funding for consulting, research, or patient education from Biogen, Genentech, Genzyme, Medimmune, MSAA, NMSS, Novartis, TSerono, and Teva.

[email protected]

SOURCE: Rensel M et al. ACTRIMS Forum 2020, Abstract P042.

WEST PALM BEACH, FLA. – Patients with pediatric-onset multiple sclerosis (POMS) have less higher education and greater use of high-efficacy disease-modifying therapy (DMT), compared with patients with adult-onset MS (AOMS), according to data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Among patients with POMS, researchers also have observed an association between fatigue and mood disorders on one hand and DMT choice on the other hand. “These findings confirm the unique features of POMS and suggest that DMT choice in POMS and AOMS may influence the frequency of fatigue and mood disorders,” said Mary Rensel, MD, staff neurologist in neuroimmunology at Cleveland Clinic’s Mellen Center for MS Treatment and Research, and colleagues.

POMS is defined as MS onset before age 18, and the disease characteristics of POMS and AOMS are distinct. The former diagnosis is rare, which has limited the amount of data collected on POMS to date.

MS Partners Advancing Technology and Health Solutions (MS-PATHS), sponsored by Biogen, is a multicenter initiative in which researchers collect MS performance measures longitudinally at each patient visit. MS-PATHS data include sociodemographic information, patient-reported outcomes (PROs), functional outcomes (FOs), MS phenotype, and DMT. Using MS-PATHS data, Dr. Rensel and colleagues sought to determine differences in sociodemographics, MS phenotype, PRO, FO, and DMT among patients with POMS and between patients with POMS and those with AOMS.

The investigators analyzed data cut 9 of the MS-PATHS database for their study. They included 637 participants with POMS and matched them with patients with AOMS, based on disease duration, in a 1:5 ratio. Dr. Rensel and colleagues categorized DMTs as high, mid, or low efficacy. They calculated descriptive statistics to characterize the study population. In addition, they compared MS FOs and PROs in the matched cohort using the Wilcoxon rank-sum test. Finally, linear regression analysis allowed the investigators to identify differences in the data set, while adjusting for important covariates.

The matched cohort included 5,857 patients with AOMS and 600 patients with POMS. The patients with AOMS had an average age of 49.8 years. About 87.5% of these patients were white, and 73.5% were female. The POMS patients had an average age of 31.49 years. Overall, 76.7% of these patients were white, and 73.2% were female. Dr. Rensel and colleagues found significant differences between the two groups in age at encounter, disease duration, race, insurance, Patient Determined Disease Steps (PDDS), education, employment, FOs, PROs, and DMT.

Patients with POMS used high-efficacy DMT more frequently than those with AOMS. The rate of depression was similar between patients with AOMS and those with POMS. Depression, anxiety, and fatigue were associated with DMT potency in AOMS, and anxiety and fatigue were associated with DMT groups in POMS.

Racial differences between POMS and AOMS have been reported previously, said Dr. Rensel. First-generation immigrant children have an increased risk of POMS, compared with other children. “In our data set, we had more Asians, more blacks, and fewer Caucasians in the POMS group,” said Dr. Rensel. People from a socioeconomically challenged environment have an increased risk of POMS, and this observation may explain the difference in insurance coverage between the POMS and AOMS groups, she added. Socioeconomic challenges also may explain the difference in the rate of higher education between the two groups.

“Why were the POMS cases associated with higher-efficacy DMT when only one oral MS DMT is [Food and Drug Administration]-approved for POMS?” Dr. Rensel asked. “This is likely due to the fact that POMS cases tend to have higher disease activity with more relapses and more brain lesions, leading to the choice of higher efficacy DMTs that are currently not FDA-approved for POMS.”

These data “may help [clinicians] caring for kids and teens, especially non-Caucasian [patients], to consider MS on the differential diagnosis,” Dr. Rensel added. “Mood disorders in POMS were as common as mood disorders in AOMS, so these should be screened for in this POMS population.”

Dr. Rensel has received funding for consulting, research, or patient education from Biogen, Genentech, Genzyme, Medimmune, MSAA, NMSS, Novartis, TSerono, and Teva.

[email protected]

SOURCE: Rensel M et al. ACTRIMS Forum 2020, Abstract P042.

WEST PALM BEACH, FLA. – Patients with pediatric-onset multiple sclerosis (POMS) have less higher education and greater use of high-efficacy disease-modifying therapy (DMT), compared with patients with adult-onset MS (AOMS), according to data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Among patients with POMS, researchers also have observed an association between fatigue and mood disorders on one hand and DMT choice on the other hand. “These findings confirm the unique features of POMS and suggest that DMT choice in POMS and AOMS may influence the frequency of fatigue and mood disorders,” said Mary Rensel, MD, staff neurologist in neuroimmunology at Cleveland Clinic’s Mellen Center for MS Treatment and Research, and colleagues.

POMS is defined as MS onset before age 18, and the disease characteristics of POMS and AOMS are distinct. The former diagnosis is rare, which has limited the amount of data collected on POMS to date.

MS Partners Advancing Technology and Health Solutions (MS-PATHS), sponsored by Biogen, is a multicenter initiative in which researchers collect MS performance measures longitudinally at each patient visit. MS-PATHS data include sociodemographic information, patient-reported outcomes (PROs), functional outcomes (FOs), MS phenotype, and DMT. Using MS-PATHS data, Dr. Rensel and colleagues sought to determine differences in sociodemographics, MS phenotype, PRO, FO, and DMT among patients with POMS and between patients with POMS and those with AOMS.

The investigators analyzed data cut 9 of the MS-PATHS database for their study. They included 637 participants with POMS and matched them with patients with AOMS, based on disease duration, in a 1:5 ratio. Dr. Rensel and colleagues categorized DMTs as high, mid, or low efficacy. They calculated descriptive statistics to characterize the study population. In addition, they compared MS FOs and PROs in the matched cohort using the Wilcoxon rank-sum test. Finally, linear regression analysis allowed the investigators to identify differences in the data set, while adjusting for important covariates.

The matched cohort included 5,857 patients with AOMS and 600 patients with POMS. The patients with AOMS had an average age of 49.8 years. About 87.5% of these patients were white, and 73.5% were female. The POMS patients had an average age of 31.49 years. Overall, 76.7% of these patients were white, and 73.2% were female. Dr. Rensel and colleagues found significant differences between the two groups in age at encounter, disease duration, race, insurance, Patient Determined Disease Steps (PDDS), education, employment, FOs, PROs, and DMT.

Patients with POMS used high-efficacy DMT more frequently than those with AOMS. The rate of depression was similar between patients with AOMS and those with POMS. Depression, anxiety, and fatigue were associated with DMT potency in AOMS, and anxiety and fatigue were associated with DMT groups in POMS.

Racial differences between POMS and AOMS have been reported previously, said Dr. Rensel. First-generation immigrant children have an increased risk of POMS, compared with other children. “In our data set, we had more Asians, more blacks, and fewer Caucasians in the POMS group,” said Dr. Rensel. People from a socioeconomically challenged environment have an increased risk of POMS, and this observation may explain the difference in insurance coverage between the POMS and AOMS groups, she added. Socioeconomic challenges also may explain the difference in the rate of higher education between the two groups.

“Why were the POMS cases associated with higher-efficacy DMT when only one oral MS DMT is [Food and Drug Administration]-approved for POMS?” Dr. Rensel asked. “This is likely due to the fact that POMS cases tend to have higher disease activity with more relapses and more brain lesions, leading to the choice of higher efficacy DMTs that are currently not FDA-approved for POMS.”

These data “may help [clinicians] caring for kids and teens, especially non-Caucasian [patients], to consider MS on the differential diagnosis,” Dr. Rensel added. “Mood disorders in POMS were as common as mood disorders in AOMS, so these should be screened for in this POMS population.”

Dr. Rensel has received funding for consulting, research, or patient education from Biogen, Genentech, Genzyme, Medimmune, MSAA, NMSS, Novartis, TSerono, and Teva.

[email protected]

SOURCE: Rensel M et al. ACTRIMS Forum 2020, Abstract P042.

womensWEST PALM BEACH, FLA. – Patients with multiple sclerosis (MS) are at increased risk for most types of infection, with the highest risk associated with renal tract infections, according to an analysis of Department of Defense data.

Susan Jick, DSc, director of the Boston Collaborative Drug Surveillance Program and professor of epidemiology and biostatistics at Boston University, and colleagues sought to understand the rates at which infections occur because they are known to be a common cause of comorbidity and death in patients with MS.

At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Jick and associates presented rates of infection in patients with MS after MS diagnosis, compared with a matched population of patients without MS. The MS cohort included patients who had MS diagnosed and treated between January 2004 and August 2017. Patients had medical history available for at least 1 year before MS diagnosis and at least one prescription for an MS disease-modifying treatment.

Patients without MS were matched to patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. For each patient, the researchers identified the first diagnosed infection of each type after cohort entry. They followed patients until loss of eligibility, death, or end of data collection.

In all, the study included 8,695 patients with MS and 86,934 matched patients without MS. The median age at cohort entry was 41 years, and 71% were female. Median duration of follow-up after study entry was about 6 years. Patients with MS were more likely to have an infection in the year before cohort entry, compared with non-MS patients (43.9% vs. 36.3%).

After cohort entry, the incidence rate of any infection was higher among patients with MS, compared with non-MS patients (4,805 vs. 2,731 per 10,000 person-years; IR ratio, 1.76). In addition, the IR of hospitalized infection was higher among MS patients (125 vs. 51.3 per 10,000 person-years; IRR, 2.43). The IR also was increased for several other types of infections, including renal, skin, fungal, pneumonia or influenza, and other infections (such as rickettsial and spirochetal diseases, helminthiases, and nonsyphilitic and nongonococcal venereal diseases). Eye or ear, respiratory or throat, and viral IRRs “were marginally elevated,” the investigators wrote.

In both cohorts, females had a higher risk of infection than males did. The rate of renal tract infection was more than fourfold higher among females, compared with males, in both cohorts. Relative to non-MS patients, however, men with MS had a higher IRR for renal tract infection than women with MS did (2.47 vs. 1.90).

“The risk for any opportunistic infection was slightly increased among MS patients,” the researchers wrote (520 vs. 338 per 10,000 person-years; IRR, 1.54). This was particularly true for candidiasis (252 vs. 166 per 10,000 person-years; IRR, 1.52) and herpes virus infection (221 vs. 150 per 10,000 person-years; IRR, 1.47). “There were few cases of tuberculosis, hepatitis B infection, or hepatitis C infection,” they noted.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four authors are employees of Bristol-Myers Squibb, and one author works for a company that does business with Celgene.

[email protected]

SOURCE: Jick S et al. ACTRIMS Forum 2020, Abstract P086.


 

womensWEST PALM BEACH, FLA. – Patients with multiple sclerosis (MS) are at increased risk for most types of infection, with the highest risk associated with renal tract infections, according to an analysis of Department of Defense data.

Susan Jick, DSc, director of the Boston Collaborative Drug Surveillance Program and professor of epidemiology and biostatistics at Boston University, and colleagues sought to understand the rates at which infections occur because they are known to be a common cause of comorbidity and death in patients with MS.

At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Jick and associates presented rates of infection in patients with MS after MS diagnosis, compared with a matched population of patients without MS. The MS cohort included patients who had MS diagnosed and treated between January 2004 and August 2017. Patients had medical history available for at least 1 year before MS diagnosis and at least one prescription for an MS disease-modifying treatment.

Patients without MS were matched to patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. For each patient, the researchers identified the first diagnosed infection of each type after cohort entry. They followed patients until loss of eligibility, death, or end of data collection.

In all, the study included 8,695 patients with MS and 86,934 matched patients without MS. The median age at cohort entry was 41 years, and 71% were female. Median duration of follow-up after study entry was about 6 years. Patients with MS were more likely to have an infection in the year before cohort entry, compared with non-MS patients (43.9% vs. 36.3%).

After cohort entry, the incidence rate of any infection was higher among patients with MS, compared with non-MS patients (4,805 vs. 2,731 per 10,000 person-years; IR ratio, 1.76). In addition, the IR of hospitalized infection was higher among MS patients (125 vs. 51.3 per 10,000 person-years; IRR, 2.43). The IR also was increased for several other types of infections, including renal, skin, fungal, pneumonia or influenza, and other infections (such as rickettsial and spirochetal diseases, helminthiases, and nonsyphilitic and nongonococcal venereal diseases). Eye or ear, respiratory or throat, and viral IRRs “were marginally elevated,” the investigators wrote.

In both cohorts, females had a higher risk of infection than males did. The rate of renal tract infection was more than fourfold higher among females, compared with males, in both cohorts. Relative to non-MS patients, however, men with MS had a higher IRR for renal tract infection than women with MS did (2.47 vs. 1.90).

“The risk for any opportunistic infection was slightly increased among MS patients,” the researchers wrote (520 vs. 338 per 10,000 person-years; IRR, 1.54). This was particularly true for candidiasis (252 vs. 166 per 10,000 person-years; IRR, 1.52) and herpes virus infection (221 vs. 150 per 10,000 person-years; IRR, 1.47). “There were few cases of tuberculosis, hepatitis B infection, or hepatitis C infection,” they noted.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four authors are employees of Bristol-Myers Squibb, and one author works for a company that does business with Celgene.

[email protected]

SOURCE: Jick S et al. ACTRIMS Forum 2020, Abstract P086.


 

womensWEST PALM BEACH, FLA. – Patients with multiple sclerosis (MS) are at increased risk for most types of infection, with the highest risk associated with renal tract infections, according to an analysis of Department of Defense data.

Susan Jick, DSc, director of the Boston Collaborative Drug Surveillance Program and professor of epidemiology and biostatistics at Boston University, and colleagues sought to understand the rates at which infections occur because they are known to be a common cause of comorbidity and death in patients with MS.

At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Jick and associates presented rates of infection in patients with MS after MS diagnosis, compared with a matched population of patients without MS. The MS cohort included patients who had MS diagnosed and treated between January 2004 and August 2017. Patients had medical history available for at least 1 year before MS diagnosis and at least one prescription for an MS disease-modifying treatment.

Patients without MS were matched to patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. For each patient, the researchers identified the first diagnosed infection of each type after cohort entry. They followed patients until loss of eligibility, death, or end of data collection.

In all, the study included 8,695 patients with MS and 86,934 matched patients without MS. The median age at cohort entry was 41 years, and 71% were female. Median duration of follow-up after study entry was about 6 years. Patients with MS were more likely to have an infection in the year before cohort entry, compared with non-MS patients (43.9% vs. 36.3%).

After cohort entry, the incidence rate of any infection was higher among patients with MS, compared with non-MS patients (4,805 vs. 2,731 per 10,000 person-years; IR ratio, 1.76). In addition, the IR of hospitalized infection was higher among MS patients (125 vs. 51.3 per 10,000 person-years; IRR, 2.43). The IR also was increased for several other types of infections, including renal, skin, fungal, pneumonia or influenza, and other infections (such as rickettsial and spirochetal diseases, helminthiases, and nonsyphilitic and nongonococcal venereal diseases). Eye or ear, respiratory or throat, and viral IRRs “were marginally elevated,” the investigators wrote.

In both cohorts, females had a higher risk of infection than males did. The rate of renal tract infection was more than fourfold higher among females, compared with males, in both cohorts. Relative to non-MS patients, however, men with MS had a higher IRR for renal tract infection than women with MS did (2.47 vs. 1.90).

“The risk for any opportunistic infection was slightly increased among MS patients,” the researchers wrote (520 vs. 338 per 10,000 person-years; IRR, 1.54). This was particularly true for candidiasis (252 vs. 166 per 10,000 person-years; IRR, 1.52) and herpes virus infection (221 vs. 150 per 10,000 person-years; IRR, 1.47). “There were few cases of tuberculosis, hepatitis B infection, or hepatitis C infection,” they noted.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four authors are employees of Bristol-Myers Squibb, and one author works for a company that does business with Celgene.

[email protected]

SOURCE: Jick S et al. ACTRIMS Forum 2020, Abstract P086.