. 2020 Aug 6;33(6):e13986. doi: 10.1111/dth.13986

TABLE 5.

expert recommendation for immunomodulators treatment and immune based dermatologic disorders

First author	Title	Patient characteristics	Recommendation	The reason	Dose adjustment
Rademaker, M.	Advice regarding COVID‐19 and use of immunomodulators, in patients with severe dermatological diseases ⁴⁶	Patient With inflammatory skin disorder being actively managed with an immunomodulator who confirmed COVID‐19 Disease	should stop the immunomodulator (s) immediately, exception of systemic corticosteroids	COVID‐19 infection being aggravated by immunomodulators and secondary bacterial infection as part of COVID‐19 complication become aggravated too	Not reported
Rademaker, M.		patient with inflammatory skin disorder being actively managed with an immunomodulator who with signs of common cold but is not formally diagnosed with COVID‐19 disease	Lowering the dose of immunomodulatory/ or temporarily stopping for 2 weeks. Exception is systemic corticosteroids.		Azathioprine: reduce to ≤0.5 mg/kg/day Ciclosporin: reduce to ≤1 mg/kg/day Methotrexate: reduce to ≤10 mg/week Mycophenolate mofetil: reduce to ≤1 g/day (mycophenolic acid to ≤720 mg/day)
Federico Bardazzi	Biologic therapy for psoriasis during the COVID‐19 outbreak is not a choice ⁴⁷	patient is stable or in good health	It is not reasonable/indicated to suspend the ongoing immunosuppressive/immunomodulatory therapy	as the risk of reactivation of the underlying pathology could add an additional risk factor to infections, including COVID‐19./inhibition of IL‐17 pathway may have beneficial effects in treating COVID‐19	Not reported
Shanshal, M.	Biological treatment uses amid the COVID‐19 era, a close look at the unresolved perplexity ⁴⁸	patients who are already on biological treatment and have tested positive for COVID‐19	Discontinuing or postponing the biological therapy until full recovery from the COVID‐19 infection.	patients with existing comorbidities will need extra precaution along with frequent clinical observation and monitoring, some patients with active infection show no symptoms or radiologic abnormalities in the initial presentation and might not realize that they have been infected	Not reported
		composed of patients who are being considered for the initiation of biological therapy	avoidance of initiation of biologic therapy for high‐risk patients		Not reported
		patients with severe psoriasis, those on potentially immunosuppressive therapies, and those presenting comorbid conditions might be at higher risk of infection.	all individuals stop biological treatment as soon as they are diagnosed with COVID‐19 infection		Not reported
Di Lernia, Vito	Biologics for psoriasis during COVID‐19 outbreak ⁴⁹	patients on biologics and on immunosuppressants for psoriasis, hidradenitis, atopic dermatitis, pemphigoid, pemphigus, and other conditions	all patients taking biologics wear such coverings or masks when outside the home and practice social distancing	it is neither practical nor logical to cease these over a few weeks while this pandemic is upon us	Not reported
Megna, M.	Biologics for psoriasis patients in the COVID‐19 era: more evidence, less fears ⁵⁰	psoriasis patients during COVID‐19 pandemic era	We strongly believe that proactive biologic discontinuation should be avoided.	interruption of biologic therapy in psoriatic patients involves a dysregulation of inflammatory cytokines that not only exacerbates psoriasis but is also likely to contribute to a more aggressive organic response to SARS‐CoV‐2, biologics for psoriasis do not increase the risk of viral infections or their complications	Not reported
Abdelmaksoud, A.	Comment on “COVID‐19 and psoriasis: Is it time to limit treatment with immunosuppressants? A call for action” ⁵¹	Older patients with moderate‐to‐severe psoriatic	Not stop systemic biologic or nonbiologic therapy and phototherapy/ interleukin 17 inhibitors should considered in the priority because have lower effects on personal immune functions	users of apremilast, etanercept, and ustekinumab are at lower risk rate of serious infection compared with those on methotrexate,	Not reported
Conforti, C.	COVID‐19 and psoriasis: Is it time to limit treatment with immunosuppressants? A call for action ⁵²	patient with psoriasis taking immunosuppressive drugs	limit and/or reduce the time of administration, preferring topical and/or drugs with a lower impact on the immune system	these drugs may cause decreased immune response and greater susceptibility to life‐threatening infections	Not reported
Conforti, C.		patient with psoriasis taking immunosuppressive drugs who confirmed COVID‐19	stop all immunosuppressive and biological therapy		Not reported
Price, K. N.	COVID‐19 and immunomodulator/immunosuppressant use in dermatology ⁵³	Psoriasis Patients treat with Corticosteroids, Tacrolimus, Cyclosporine, Mycophenolate mofetil, Azathioprine, Methotrexate	Consider stopping when viral symptoms present especially with known or potential exposure	Broad immunosuppression across multiple cytokine axes with immunosuppressants has the potential to increase susceptibility, persistence, and reactivation of viral infections. Immunosuppressants decrease cytokines that recruit and differentiate immune cells needed to clear the infection. In addition, inflammatory mediators can become hyperactivated, resulting in a “cytokine storm,” which is the primary cause of death in severe disease.	Not reported
		psoriasis Patients treat with Infliximab, Etanercept, Certolizumab, Adalimumab, Anakinra (IL‐1)	Continue if viral symptoms are mild, consider stopping if viral symptoms worsen or high fever develops		Not reported
		psoriasis Patients treat with Dupilumab (IL‐4)	Continue unless severe symptoms present		Not reported
		psoriasis Patients treat with Brodalumab (IL‐17), Secukinumab (IL‐17a), Ixekizumab (IL‐17a), Ustekinumab (IL‐12/23), Guselkumab (IL‐23)	Continue if viral symptoms are mild, consider stopping if viral symptoms worsen or high fever develops		Not reported
		psoriasis Patients treat with Rituximab	Consider stopping when viral symptoms present especially with known or potential exposure.		Not reported
		psoriasis Patients treat with Apremilast	Continue unless severe symptoms present		Not reported
Wang, C.	COVID‐19 and the use of immunomodulatory and biologic agents for severe cutaneous disease: An Australia/New Zealand consensus statement ⁵⁴	Patients on immunomodulators, including biologic agents and new small molecular inhibitors for cutaneous disease, with suspected or confirmed COVID‐19 disease	All immunomodulators used for skin diseases should be immediately withheld, exception of systemic corticosteroid therapy,	immunosuppression is thought to increase susceptibility and cause more severe infection and atypical presentations of coronavirus infections in immunocompromised hosts, including prolonged incubation periods, persistent asymptomatic viral shedding, diarrh oea, weight loss and encephalitis as primary manifestations	Conventional immunomodulators should be withheld for 31 days from infection onset and only recommenced after complete resolution of illness and/or confirmation of negative PCR testing indicating no viral shedding Systemic corticosteroids: Reduce to 10 mg/day predniso(lo)ne or equivalent in a graduated manner .
		on immunomodulators, who develop symptoms or signs of an upper respiratory tract infection, but COVID‐19 is not yet confirmed	dose reduction or temporarily cessation for 1–2 weeks	there is currently insufficient evidence to suggest that COVID ‐19 infection is aggravated by immunomodulators used in skin disease, however all COVID‐19 infections should be considered serious	Azathioprine: Reduce to ≤0.5 mg/kg/day Ciclosporin: Reduce to ≤1 mg/kg/day Methotrexate: Reduce to ≤10 mg/week Mycophenolate mofetil: Reduce to ≤1 g/day Systemic corticosteroids: Reduce to 10 mg/day predniso(lo)ne or equivalent in a graduated manner Biologics: extending the time between dosages. Retinoids: No dose adjustment required
		Well patients on immunomodulators	Immunomodulators and biologics should be continued	Discontinuation of biologic therapy may result in a loss of treatment response when rechallenged and/or development of drug antibodies	Not reported
		Children patients on immunomodulators,	Dose reduction or cessation of immunomodulators and biologics is not necessary	Not reported	Not reported
		Organ Transplant/Bone marrow transplant patients	Immunosuppressive treatments (eg, prednisone, ciclosporin, tacrolimus, azathioprine, mycophenolate, etc.) should not be stopped	Not reported	Not reported
Arora, G	The COVID‐19 outbreak and rheumatologic skin diseases ⁵⁵	Patients on Disease‐modifying antirheumatic drugs (DMRD)s, biologics or other immunosuppressive medications	Required to consult their rheumatologist and stop these drugs during an infection	Because patients with rheumatic disease are more susceptible to the COVID‐19 virus either because of the rheumatalogic disease itself or the medications used to treat their underlying disease.	Not reported
Arora, G	The COVID‐19 outbreak and rheumatologic skin diseases ⁵⁵	Non‐infected patients	Advised to continue their medication during the epidemic		Not reported
Kansal, NK	COVID‐19, syphilis, and biologic therapies for psoriasis and psoriatic arthritis: A word of caution ⁵⁶	Patients with psoriasis and psoriasis arthritis	Considering the risk to benefit ratio before discontinuing drugs and monitoring the patients who continue to receive the therapy	Because the prognosis of COVID‐19 cannot be predicted in individual cases (particularly in middle aged and older patients, with co‐morbidities like diabetes mellitus or cardiovascular disease etc, if they are being treated with biologics).	Not reported
Plachouri, KM	The management of biologics in dermatologic patients in the 2019‐nCoV era ⁵⁷	Dermatologic patients	Postpone initiation of biologic treatments in this particular period	The lack of sufficient data concerning the interaction of SARS‐CoV‐2 and biologics is also an important factor that should be taken into consideration when examining the option of initiating therapy with the latter. Another logistic parameter that should not be underestimated is the need of frequent careful monitoring under such treatments that includes both regular laboratory examinations as well as routine dermatologic follow‐up visits, which could constitute a problem under the emerging societal circulatory restrictions that are posed in order to control the pandemic transmission	Not reported
Brownstone, ND	Novel Coronavirus Disease (COVID‐19) and Biologic Therapy in Psoriasis: Infection Risk and Patient Counseling in Uncertain Times ⁵⁸	Psoriatic patients with following risk factors: Any active infection, including COVID‐19 COVID‐19 risk factors including: age over 60, cardiovascular disease, hypertension, lung disease, diabetes, or cancer Concomitant immunosuppression (eg, methotrexate, prednisone, cyclosporine) Immunosuppressive condition (eg, HIV) History of infections while on biologic Mild‐to‐moderate underlying psoriasis High risk of exposure to COVID‐19 virus (eg, endemic area, health care worker, nursing home resident, household member or co‐worker with COVID‐19 infection) Short duration of COVID‐19 pandemic	favoring biologic discontinuation or reduction in immunomodulatory regimen, if reduction is needed option include: Temporary discontinuation of the biologic Reduction in biologic dose frequency Transition to an alternative biologic Reduction or discontinuation of concomitant immunosuppressants (eg, methotrexate) Increase in use of topical agents, home phototherapy, or other non‐immunosuppressive medications	These recommendations are based on rate of infections in previous clinical trials studies about biologic and immunosuppressive drugs in psoriatic patients	Not reported
		Psoriatic patients with following risk factors: Young age No COVID‐19 high risk co‐morbidities Biologic monotherapy Severe underlying psoriasis or psoriatic arthritis, with history of rapid flares or unstable subtypes (pustular, erythrodermic) No concomitant immunosuppressive conditions Low risk of exposure to COVID‐19 virus Long duration of COVID‐19 pandemic	favoring biologic continuation		Not reported
		Patients who test positive for COVID‐19 infection	Advising to hold their biologic dose until their infection clears.		This requires untill improvement in respiratory symptoms, and two negative COVID‐19 test performed 24 hours apart. if COVID‐19 retesting is not available, restarting biologic therapy until 30 days after resolution of fever and respiratory symptoms
Villani, A	Patients with advanced basal cell carcinomas in treatment with sonic hedgehog inhibitors during the coronavirus disease 2019 (COVID‐19) period: Management and adherence to treatment ⁵⁹	Patients with advanced basal cell carcinoma receiving treatment with the hedgehog pathway inhibitors sonidegib and vismodegib during the COVID‐19 period	Continuing therapy. Dose adjustment to prolong treatment duration, when possible.	Based on their analysis on 37 patients at Italian referral center for skin cancer diagnosis and management	Not reported
Gisondi, P	Risk of hospitalization and death from COVID‐19 infection in patients with chronic plaque psoriasis receiving a biological treatment and renal transplanted recipients in maintenance immunosuppressive treatment ⁶⁰	Patients with chronic plaque psoriasis receiving a biological treatment and renal transplanted recipients in maintenance immunosuppressive treatment	There is no need to discontinue their therapies	There is no early signal of an increased hospitalization or death from COVID‐19. Based on retrospective observational study in verona	Not reported
ShakShouk, H	Treatment considerations for patients with pemphigus during the COVID‐19 pandemic ⁶¹	Patients with pemphigus and without active infection	postponing rituximab infusions temporarily	Delaying peak patient immunosuppression during peak COVID‐19 incidence to reduce the risk of adverse outcomes.	Not reported
		Patients with pemphigus and without active infection	glucocorticoids and steroid‐sparing immunosuppressive agents, such as azathioprine and mycophenolate mofetil, should be tapered to the lowest effective dose	Their nonspecific immunosuppressive effects increase infection risk, among other complications, in a dose‐dependent manner.	Not reported
		Patients with pemphigus and active COVID‐19 infection	postponing rituximab infusions temporarily	Delaying peak patient immunosuppression during peak COVID‐19 incidence to reduce the risk of adverse outcomes.	Not reported
		Patients with pemphigus and active COVID‐19 infection	In active COVID‐19 infection, immunosuppressive steroid‐ sparing medications should be discontinued when possible	Their nonspecific immunosuppressive effects increase infection risk, among other complications, in a dose‐dependent manner.	Not reported
Jic ZA	United States Cutaneous Lymphoma Consortium Recommendations for Treatment of Cutaneous Lymphomas During the COVID‐19 Pandemic ⁶²	Low risk patients with cutaneous lymphomas	Low‐risk therapies that can be utilized at home should be continued for all patients. Home‐based NBUVB and heliotherapy can be continued or initiated.	The risks of travel and exposure likely outweigh the benefit of in‐office treatments such as ultraviolet light therapy and total body electron beam radiation therapy.	Not reported
		Intermediate low risk patients with cutaneous lymphomas	Therapies may be continued, but dose adjustments may be advised on an individual basis. Initiation of these therapies may be postponed using low‐risk bridge therapies short term. Increasing or initiation of a retinoid or interferon should be considered in cases that necessitate the removal of other high‐risk therapies.	Not reported	Not reported
		Intermediate high risk patients with cutaneous lymphomas		Not reported	Not reported
		High risk patients with cutaneous lymphomas	May require travel to the clinic or hospital. These should only be utilized in the highest risk patients and the additional risks of therapy‐related travel should be considered. Infusion regimens may be adjusted to increase treatment intervals. Allogeneic stem cell transplant and treatment with CHOP, alemtuzumab, fludarabine are strongly discouraged, Consider alternative lower risk therapies whenever possible.	Allogeneic stem cell transplant and treatment with CHOP, alemtuzumab, fludarabine are strongly discouraged during the pandemic because they often lead to significant cytopenias that are known risk factors for COVID‐19 complications.	Romidepsin and mogamulizumab may be considered on individual basis with extended intervals and lower doses.
Torres, T	Managing Cutaneous Immune‐Mediated Diseases During the COVID‐19 Pandemic ⁶³	patients with cutaneous immune‐mediated diseases (including psoriasis, atopic dermatitis, and hidradenitis suppurativa) and without active COVID‐19 infection	Continue their treatment even during the COVID‐19 outbreak	Preventing disease fares Immunosuppressive and immunomodulatory drugs may potentially control the “cytokine storm”	Not reported
Torres, T		Patients with cutaneous immune‐mediated diseases (including psoriasis, atopic dermatitis, and hidradenitis suppurativa) and with active COVID‐19 infection	Withhold immunosuppressive or biologic treatment	Not reported	Not reported
Megna, M	Biologics for psoriasis in COVID‐19 era: what do we know? ⁶⁴	Psoriatic patients without COVID‐19 infection	Treatment discontinuation should be avoided	Unnecessary biologic discontinuation would lead to a worsening of psoriasis and psoriatic arthritis in a high percentage of the cases. As a consequence, there may be higher disease burden, destructive impact on quality of life, as well as increased health care costs due to the augmented number of consultations and recovery. Furthermore, the unavoidable subsequent return to biologic therapy could be associated with switching toward higher cost drugs, due to the well‐known lower efficacy of biologics in the same patient after their interruption	Not reported
Megna, M		Psoriatic patients with COVID‐19 infection	Treatment discontinuation		Not reported
Amerio, P	COVID‐19 and psoriasis: should we fear for patients treated with biologics ⁶⁵	Psoriatic patients	The treatment of psoriatic patients with biologicals should not be discontinued during the time of this pandemic	Based on literature review	Not reported
Amerio, P		elderly patients with coexisting morbidities such as hypertension, diabetes and obesity that enhance their chance of developing, if ever infected, a more severe disease; when patients develop flu like or COVID‐19 specific (anosmia, asthenia) symptoms and if are exposed to high risk contact with infected people	Suspend the treatment should be made	Based on literature review	Not reported