Autoimmune and Molecular Insights into Skin Psoriasis and psoriatic Arthritis

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 The Role of Biologics

Autoimmune and Molecular Insights into
Skin Psoriasis and psoriatic Arthritis

KARACHI. Prof. Joachim W. Herzig from Johannes Gutenberg University, Germany was the guest speaker at a CME programme organized by Rheumatology Department of Liaquat National Hospital & Medical College, Karachi in collaboration with M/s Tranz-Life here on April 28th, 2018. Prof. Joachim Herzig discussed in detail the Role of Biologics in Autoimmune and Molecular Insights into Skin Psoriasis & Psoriatic Arthritis.

Speaking at the occasion Prof. Herzig said that Psoriasis is a chronic non communicable disease, it is painful, have disfiguring effects and cause disabilities. Physical and psychosocial impact of Psoriasis and psoriatic Arthritis makes the patient angry, upset, they suffer from social discrimination, depression and anxiety, negative social impact, and lost time from work. Patient is worried and feel guilty passing on the disease to their children, prefer not to be seen in the public during flare and always try to cover the body with long clothes. Psoriasis is an autoimmune disease, abnormally excessive and rapid growth of the epidermal layer. Abnormal production of skin cells especially during wound repair. Its treatment should be effective and reasonable, he added.

Use of biologics Prof. Herzig pointed out is not much developed and are less used due to concerns about the risks associated with its uses. TNF inhibitors, he stated are the first generation Biologics for psoriasis and Psoriatic arthritis while IL-12/IL-23 inhibitors and IL-17A inhibitors are the second and third generation biologics respectively. New generation biologics represent an advance over the older TNF-Inhibitors, they are more specific blocking effects, more effective and well tolerated. Biological therapies for psoriasis have previously been associated with a decrease in efficacy over time. Extended follow-up showed the efficacy to be maintained with secukinumab and ixekizumab. Almost 30% of psoriasis patients are affected by psoriatic arthritis which is a chronic immune mediated, inflammatory disease and is characterized by peripheral and axial arthritis, dactylitis and enthesists.


Prof. Joachim W. Herzig (third from Left) replying to questions during a Seminar on the Role of Biologics
in Autoimmune and Molecular Insights into Skin Psoriasis & Psoriatic Arthritis held at Liaquat National
Hospital
Karachi. Other panelist sitting on the dais from (L to R) are Dr. Shaheen Naveed, Dr. Sadia
Tabassum,
Dr. Tahira Perveen, Dr. Samina Ghazanavi, Prof. Riaz Qureshi and Dr. Sharaf Ali Shah.

Continuing, Prof. Herzig stated that more than 120 million people worldwide suffer from psoriasis many of whom are undertreated and are not offered the new treatment modalities. Prof. Herzig described the genetic predisposition of psoriasis, the effect of major gene associations, the role of HLA-Cw6 in the pathogenesis of psoriasis and the association of PSORS2/CARD14 mutation with psoriasis. He discussed at length the immunogenic model of psoriasis with activation of plasmatoid dendritic cells, initiation of the pathogenic inflammatory cascade through production of IFN-gamma and activation of IL23/17 axis and the development of psoriatic phenotype. He elaborated upon the auto-amplification signals through IL-17 that stimulate keratinocytes to produce chemo-attractants that further recruited IL-17 producing T-cells. He stressed that the newer biologics represented an advance over older agents in that they were more effective with a more specific blocking effect and were well tolerated. Efficacy with time was maintained with newer biologics that blocked IL-17A. He shared the data from CLEAR, SCULPTURE, UNCOVER-3 and FUTURE-2 studies and the response rates to secukinumab, Ixekizumab and Brodalumab, all IL-17A inhibitors.

Talking about Brodalumab and newer biologics, Prof. Herzig said that anti IL-17RA (subnit of IL-17A receptors) monocolonial antibody, inhibits activities of IL-17AQ, Il-17E/IL-25, targets a broader spectrum of IL-17 compared to secukinumab and lxekinumab but carries a boxed warning for suicidal ideation. Third generation biologics may be regarded as the new standard of treatment for psoriasis and Psoriatic Arthritis. Due to their higher efficacy, they might be considered as the first line biologic therapy for moderate to severe psoriasis, he concluded.

Dr. Sana Gul, consultant Dermatologist at JPMC Karachi presented a case of psoriasis and psoriatic arthritis who presented with lower backache and stiffness and restriction of movements in various joints. He was treated with etanercept, a first generation biological with a very good response initially but poor response later.

Dr. Tahira Perveen, Head of Rheumatology Department at Liaquat National Hospital & Medical College, Karachi also presented a case of psoriatic arthritis who showed a 50% reduction in symptoms when etanercept was administered. She highlighted the importance of upgrading the treatment, may it be the conventional DMARDs in proper dosage or the biologics. A treat to target approach should be employed for peripheral and axial arthritis with a target of remission or minimal disease activity. Exercise, physical therapy and occupational therapy, weight reduction and patient’s education are the non-pharmacological treatments. In patients with severe disease who already have erosive disease and functional limitation, TNF inhibitors are preferred as first line therapy rather than a conventional non- biologic DMARDs. Other biologic DMARDs (Secukinumab or Ustekinumab) are alternative to a TNF inhibitors, she further added.

Dr. Sharaf Ali Shah, Consultant Dermatologist taking part in panel discussion said that Psoriasis is common and global problem. It can be diagnosed clinically. Moderate to severe cases needs systemic treatment which are managed by Dermatologists. It is a lifelong disease. When psoriasis is associated with arthritis it is challenging. At present in Pakistan best systemic drug for psoriasis is methotrexate, which is time tested, it is less expensive, easily available, weekly doses but the problem is its side effects and one has to monitor the patient closely. We have to counsel the patients because counseling is very important in chronic diseases like psoriasis. Retinoids are the other drugs for the treatment of psoriasis, they work but particularly when psoriasis is associated with arthritis, Retinoids may not be the right choice. Biologics are used all over the World with good results but these are very expensive. One year treatment cost more than ten thousand dollar and very few patients can afford it because we do not have insurance system in Pakistan. If we counsel the patient well methotrexate is the best option, he added.


Dr. Israr Nasir, presenting Ajrak to Prof. Joachim W. Herzig (Guest Speaker) at a Seminar on the
Role of Biologics in Autoimmune and Molecular Insights into Skin Psoriasis & Psoriatic Arthritis
held at Liaquat National Hospital Karachi recently. On Right Dr. Tahira Perveen presenting
shield to Mr. Shahsul Islam, Managing Director of Tranz-Life.

Prof. Riaz Qureshi, Professor of Family Medicine at AKU said that chronic pain leads to depression, one third of our patients are psychiatric patients and if we treat depression lot of improvement can be seen in these patients. They need counseling and family support. Hypnopathy helps to improve the patients and lot of non-doctors are practicing Hypnopathy. Family Medicine is need of the community, he added.

Dr. Samina Ghazanavi, Consultant Internal Medicine at LNH stated that psoriasis is very common problem. People are not aware about the specialty and go to the orthopedic surgeons. It is lifelong disease, we really need to counsel the patients to visit their physician regularly. Alternate therapy like cupping has good results and medical as well as non-medical people has started it. Dr. Sadia Tabassum, Consultant Dermatologist from AKUH in her remarks stated that psoriasis is very common diseases and psoriasis in the nail is always a challenge and we have to be very careful while treating these patients. Dr. Shaheen Naveed Consultant Dermatologist from LNH said that psoriasis is manageable and not curable disease. Joint pain is the major common problem with psoriasis and counseling plays very important role in its management.

Earlier, in her welcome address Dr. Tahira Perveen appreciated the presence of Prof. Herzig to update the knowledge of local healthcare professionals and said that there are only a handful of rheumatologists in Pakistan and no pediatric rheumatologist. Dr. Israr Nasir, Head of Department of Molecular pathology, LNH, gave the concluding remarks and thanked the participants and guest speaker.

The meeting was sponsored by M/s Tranz-Life, an emerging company paving the future of healthcare. The mission of Tranz-Life is to be partners in innovation for disease management, collaborating with centers of excellence for disease awareness and clinical research and supporting informed patient decisions. Tranz-Life also offers its services to pharmaceutical industry for their growth transformation through contract sales and patient awareness and assistance programs.

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